Nuclide Chemistry

Group Nuclide Chemistry
Nuclide Chemistry Group (April 2022)

We are a team of PhD students, master students, postdocs and technicians with expertise in chemistry, biochemistry, biology and pharmaceutical sciences working together towards our common goals on diverse projects in the field of radiopharmaceutical sciences as outlined below.

Radiopharmaceutical sciences is an interdisciplinary field of applied research that combines expertise in physics, (radio)chemistry, (radio)biology, (radio)pharmacy and (nuclear) medicine with the aim to develop and investigate radiopharmaceuticals in view of their clinical application.

The development of radiopharmaceuticals for tumor targeting includes the design, synthesis and radiolabeling of tumor-specific ligands, their preclinical in vitro and in vivo evaluation and – in an ideal case – their clinical translation and application in nuclear medicine/oncology.

Nuclear imaging makes use of radiopharmaceuticals that – based on the employed radionuclide – emit gamma-radiation or positrons for Single Photon Emission Computed Tomography (SPECT) and Positron Emission Tomography (PET), respectively. The detection of the emitted radiation provides information about (patho)physiological processes on a molecular level and enables diagnosis and staging of a (cancer) diseases.

Targeted radionuclide therapy or endoradiotherapy makes use of radiopharmaceuticals that – based on the employed radionuclide – emit alpha particles, beta minus particles and/or Auger electrons. The specific accumulation of therapeutic radiopharmaceuticals in malignant lesions enables direct irradiation of cancer cells and is, thus, a strategy of particular value for the treatment of metastatic disease.

Nuclear imaging is most often employed for the staging and restaging of cancer diseases before and after therapy. It enables the detection of metastatic disease and demonstrates whether the applied therapy is effective in reducing the tumor burden. The concept of “radiotheragnostics” using target-specific radiopharmaceuticals pursues an additional goal in that the diagnostic image provides information about the expression of a specific therapeutic target which is useful for subsequent application of radionuclide therapy. This concept has been implemented in clinical routine for patients with cancer types that express for example the somatostatin receptor or prostate-specific membrane antigen for which targeted radionuclide therapies exist. In future, radioimaging agents may also serve for the selection of patients with diseases who could profit from other treatment options such as tumor target-specific (immuno)therapies.

The research of our group is dedicated to the design and evaluation of small-molecular-weight tumor targeting radioligands for theragnostic application, among those are radioconjugates for folate receptor (FR)-targeting as well as for targeting the prostate-specific membrane antigen (PSMA).

Our goal is to optimize the pharmacokinetic profile of the radioligands by various chemical modifications such as the derivatization with albumin-binding entities.

A major interest lies in the application and (radio)biological investigation of different radiation types using non-standard (exotic) radionuclides, which are promising for the development of the theragnostic concept.

In view of a therapeutic application, we are interested in the combination of targeted radionuclide therapy with other cancer treatments (e.g. chemotherapy, immunotherapy).

Research Interests

The development of radiopharmaceuticals with favorable pharmacokinetics requires the synthesis of compound libraries to gain knowledge about structure-activity relationships, which can subsequently be used for structural optimization. For this reason, our research group established synthetic methods for the fast and easy preparation of a broad range of structurally modified tumor-targeting folate conjugates.

folate syntehsis
Schematic overview of solid-phase synthesis routes for the preparation of folate conjugates. (Figure reprinted with permission from Deberle et al. Bioconjug Chem 2021, 32, 1617. Copyright 2022 American Chemical Society)

The folate radioconjugates accumulated specifically in folate receptor (FR)-positive tumor tissue, however, a significant amount of activity was retained in the kidneys. A major breakthrough was achieved by the derivatization of folate radioconjugates with an albumin-binding entity. The enhanced blood circulation of these novel class of folate radioconjugates resulted in an increased uptake of activity in the tumor, but reduced retention in the kidneys.

This promising approach was translated also to PSMA-targeted radioligands. It resulted in the development of new PSMA radioligands that show great potential for therapeutic application. Current projects focus on the optimization of the pharmacokinetic properties of these and other tumor targeting agents using different types of albumin binder and linker entities, respectively.

PSMA ligand design
Design, synthesis and preclinical evaluation of a novel class of PSMA-targeting radioligands equipped with ibuprofen as a weak albumin-binding entity in order to improve the pharmacokinetic properties. (Figure adapted from an article published by Deberle & Benesova et al. Theranostics 2020,10:1678. (This is an open access article distributed under the terms of the Creative Commons Attribution License; Authors retain copyright of the article).

Non-standard (exotic) radionuclides are developed and produced by the Radionuclide Development group (headed by Dr. Nicholas van der Meulen).

Radionuclide Development

The group is particularly interested in radionuclides of the same element (radioisotopes) which allow the preparation of chemically identical radiopharmaceuticals for imaging and therapy, respectively. Scandium comprises three medically interesting radioisotopes: 43Sc and 44Sc are useful for positron emission tomography (PET) and 47Sc is a radioisotope for therapeutic application and single photon emission computed tomography (SPECT). Over the last decade we have been investigating scandium radioisotopes in several preclinical studies.

A large number of pioneering studies have been performed with terbium sister radioisotopes. Terbium is unique as it comprises four radioisotopes for all four modalities in nuclear medicine, including SPECT (155Tb), PET (152Tb), alpha (149Tb) and beta radionuclide therapy (161Tb). Over the last decade, we have performed studies with all four radioisotopes in preclinical settings.

Tb sister isotopes
Terbium sister radioisotopes: 149Tb, 152Tb, 155Tb and 161Tb. Nuclide labels adapted from Karlsruhe Nuclide Chart

Currently, several preclinical projects are on-going with terbium sister radioisotopes in the group and in collaboration with external partners.

161Tb is the most advanced in terms of production and preclinical investigations. Tumor-cell based in vitro studies, in which the effect of 161Tb-PSMA-617 was compared to that of 177Lu-PSMA-617, demonstrated the advantage of using 161Tb over 177Lu due to the co-emission of a substantial number of conversion and Auger electrons.

Cell viability
Viability of PC-3 PIP tumor cells (PSMA-expressing prostate cancer cells) after incubation with 161Tb-PSMA-617 or 177Lu-PSMA-617 compared to untreated controls (set as 100%). (Figure adapted from Müller et al. Eur J Nucl Med Mol Imaging 2019, 46, 1919; This is an open access article distributed under the terms of the Creative Commons CC BY license, which permits unrestricted use, distribution, and reproduction in any medium; Springer Nature).

 

Recently, new projects have been initiated with regard to more in-depth studies using other exotic radionuclides such as 175Yb and 165Er.

Over the last years, we have been investigating the radiosensitizing effects of chemotherapeutic agents (e.g.  the antifolate pemetrexed).

Our group investigated the effect of radiation to enhance the tumor response to immunotherapy. In a recently performed preclinical study, our group demonstrated the effect of 177Lu-DOTA-folate as an immune stimulus to enhance anti-CTLA-4 immunotherapy in a syngeneic breast tumor mouse model.

Combination therapy
(A) Survival curves of mice of each group (Kaplan-Meier plot); (B-E) Graphs representing the relative tumor volumes of sham-treated control mice (B); mice that received only 177Lu-DOTA-folate (C); mice that received anti-CTLA-4 immunotherapy (D); and mice that received a combination of both treatment modalities (E). (Figure adapted from Guzik et al. Eur J Nucl Med Mol Imaging 2021, 48, 984; This is an open access article distributed under the terms of the Creative Commons CC BY license, which permits unrestricted use, distribution, and reproduction in any medium; Springer Nature).

18F-AzaFol, a PET agent for imaging folate receptor-positive tumors, was investigated in a multicenter clinical trial at three hospitals in Switzerland (NCT03242993).

Several projects are on-going with regard to first-in-man applications of novel PSMA-targeting radioligands and for the investigation of non-standard radionuclides.

The application of 152Tb-PSMA-617 for imaging of prostate-specific membrane antigen (PSMA)-positive prostate cancer, was demonstrated in a patient with metastatic castration-resistant prostate cancer (mCRPC) at Zentralklinik, Bad Berka, Germany.

152Tb-PSMA-617
PET/CT scans (transversal slices through the upper abdomen at the level of the liver and spleen) obtained at (A) 50 min, (B) 2 h, (C) 18.5 h, and (D) 25 h, respectively after injection of 140 MBq 152Tb-PSMA-617, clearly demonstrating a PSMA-avid bone metastasis in the ventrolateral part of the left 7th rib (red arrow) with maximum uptake at 18.5 and 25 h p.i. (Figure reproduced from Müller et al. EJNMMI Research 2019, 9, 68; This is an open access article distributed under the terms of the Creative Commons CC BY license, which permits unrestricted use, distribution, and reproduction in any medium; Springer Nature).

Marie Curie Award 2021 (EANM, Barcelona, Spain - virtual event)

In October 2021, Viviane Tschan* received the Marie Curie Award at the Annual Meeting of the European Association of Nuclear Medicine (EANM).

*PhD student in the group from 2018-2022

Marie Curie Award 2018 (EANM, Düsseldorf, Germany)

In October 2018, PD Dr. Cristina Müller received the Marie Curie Award at the Annual Meeting of the European Association of Nuclear Medicine (EANM).

Ruzicka Prize 2014 (ETH Zurich, Switzerland)

In November 2014, PD Dr. Cristina Müller received the Ruzicka Prize of the ETH Zurich. 

The Ruzicka Prize, named after the ETH professor and Nobel laureate Leopold Ruzicka, is considered one of the most important awards for the promotion of young scientists in the field of chemistry in Switzerland.

Presentation Prize 2021 (Doktorandentag, Institute of Pharmaceutical Sciences, ETH Zurich, Switzerland)

In February 2021, Luisa Deberle* won the Award for Best Oral Presentation

Presentation title: "Novel Synthetic Strategies for the Development of Diverse Folate Radioconjugates"

*PhD student in the group from 2018-2022

Presentation Prize 2019 (SGNM, St. Gallen, Switzerland)

In June 2019, PD Dr. Cristina Müller was awarded with the Presentation Prize 2019  of the Swiss Society of Nuclear Medicine (SGNM)

Presentation title: "161Tb-based Prostate Cancer Therapy: Investigation of the 177Lu-PLUS Effect"

August-Abegg-Fonds Prize 2018 (Doktorandentag, Institute of Pharmaceutical Sciences, ETH Zurich)

Christoph Umbricht* was awarded for the best oral presentation

Presentation title: "Preclinical development of novel PSMA-targeting radioligands - modulation of albumin-binding properties to improve prostate cancer therapy"

*PhD student in the group from 2015-2019

Poster Prize 2021 (77th Annual Meeting of the Swiss Society of Urology, Interlaken, Switzerland)

In September 2021, Viviane Tschan* was awarded a Poster Prize in the "Basic Science" Category

Presentation title: "Improved Radionuclide Therapy of Prostate Cancer - Preclinical Comparison of the Albumin-binding [177Lu]Lu-Ibu-DAB-PSMA to [177Lu]Lu-PSMA"

*PhD student in the group from 2018-2022

Best Virtual Poster Award 2021 (Swiss Chemical Society and DSM Nutritional Products)

In September 2021, Luisa Deberle* was awarded the Best Virtual Poster in the "Medicinal Chemistry" Category

Poster title: "Novel Synthetic Strategies Enable the Efficient Development of Folate Conjugates for Radiotheragnostic Application"

*PhD student in the group from 2018-2022

Alavi-Mandell Award 2022 

In June 2022, Patrycja Guzik* received the Alavi-Mandell Award as a First Author of the following publication : 

"Identification of a PET Radiotracer for Imaging of the Folate Receptor-α: A Potential Tool to Select Patients for Targeted Tumor Therapy"

Authors: Patrycja Guzik, Hsin-Yu Fang, Luisa M. Deberle, Martina Benešová, Susan Cohrs, Silvan D. Boss, Simon M. Ametamey, Roger Schibli, Cristina Müller*

*PhD student in the group from 2017-2021

Best Paper 2020 in Eur J Nucl Med Mol Imaging

In October 2021, the following article was selected for the EANM Springer Prize (one out of three)

"Terbium-161 for PSMA-targeted radionuclide therapy of prostate cancer"

Authors: Cristina Müller*, Christoph A. Umbricht, Nadezda Gracheva, Viviane J. Tschan, Giovanni Pellegrini, Peter Bernhardt, Jan Rijn Zeevaart,  Ulli Köster, Roger Schibli, Nicholas P. van der Meulen

Award for the best publication in EJNMMI Research in 2018

44Sc-PSMA-617 for radiotheragnostics in tandem with 177Lu-PSMA-617—preclinical investigations in comparison with 68Ga-PSMA-11 and 68Ga-PSMA-617

Authors: Christoph A. Umbricht, Martina Benešová, Raffaella M. Schmid, Andreas Türler, Roger Schibli, Nicholas P. van der Meulen and Cristina Müller*

Next Generation PSMA: PCF ProsTIC Global Knowledge Exchange Webinar
Krebsforschung Schweiz - Unterstützte Forschungsprojekte: Forschenden-über-die-Schulter-geschaut/
Marie Curie Award 2018 (EANM, Düsseldorf, Germany)
Ruzicka Prize 2014 (ETH Zurich, Switzerland)
  • Corpetti M, Müller C, Beltran H, de Bono J, Theurillat JP
    Prostate-specific membrane antigen–targeted therapies for prostate cancer: towards improving therapeutic outcomes
    European Urology. 2024; 85(3): 193-204. https://doi.org/10.1016/j.eururo.2023.11.018
    DORA PSI
  • Favaretto C, Grundler PV, Talip Z, Köster U, Johnston K, Busslinger SD, et al.
    Terbium-149 production: a focus on yield and quality improvement towards preclinical application
    Scientific Reports. 2024; 14(1): 3284 (12 pp.). https://doi.org/10.1038/s41598-024-53610-2
    DORA PSI
  • Fricke J, Westerbergh F, McDougall L, Favaretto C, Christ E, Nicolas GP, et al.
    First-in-human administration of terbium-161-labelled somatostatin receptor subtype 2 antagonist ([161Tb]Tb-DOTA-LM3) in a patient with a metastatic neuroendocrine tumour of the ileum
    European Journal of Nuclear Medicine and Molecular Imaging. 2024; 51: 2517-2519. https://doi.org/10.1007/s00259-024-06641-w
    DORA PSI
  • Sarogni P, Brindani N, Zamborlin A, Gonnelli A, Menicagli M, Mapanao AK, et al.
    Tumor growth-arrest effect of tetrahydroquinazoline-derivative human topoisomerase II-alpha inhibitor in HPV-negative head and neck squamous cell carcinoma
    Scientific Reports. 2024; 14(1): 9150 (10 pp.). https://doi.org/10.1038/s41598-024-59592-5
    DORA PSI
  • Song Y, Zou J, Castellanos EA, Matsuura N, Ronald JA, Shuhendler A, et al.
    Theranostics - a sure cure for cancer after 100 years?
    Theranostics. 2024; 14(6): 2464-2488. https://doi.org/10.7150/thno.96675
    DORA PSI
  • Vaccarin C, Mapanao AK, Deberle LM, Becker AE, Borgna F, Marzaro G, et al.
    Design and preclinical evaluation of a novel prostate-specific membrane antigen radioligand modified with a transthyretin binder
    Cancers. 2024; 16(7): 1262 (13 pp.). https://doi.org/10.3390/cancers16071262
    DORA PSI
  • Wallimann RH, Hensinger H, Müller C, Schibli R, Kneuer R, Schindler P
    Liquid chromatography ICP-MS to assess the stability of 175Lu- and natGa-based tumor-targeting agents towards the development of 177Lu- and 68Ga-labeled radiopharmaceuticals
    Pharmaceutics. 2024; 16(3): 299 (13 pp.). https://doi.org/10.3390/pharmaceutics16030299
    DORA PSI
  • Beyer D, Vaccarin C, Deupi X, Mapanao AK, Cohrs S, Sozzi-Guo F, et al.
    A tool for nuclear imaging of the SARS-CoV-2 entry receptor: molecular model and preclinical development of ACE2-selective radiopeptides
    EJNMMI Research. 2023; 13(1): 32 (14 pp.). https://doi.org/10.1186/s13550-023-00979-2
    DORA PSI
  • Busslinger SD, Becker AE, Vaccarin C, Deberle LM, Renz M-L, Groehn V, et al.
    Investigations using albumin binders to modify the tissue distribution profile of radiopharmaceuticals exemplified with folate radioconjugates
    Cancers. 2023; 15(17): 4259 (19 pp.). https://doi.org/10.3390/cancers15174259
    DORA PSI
  • Ermini ML, Summa M, Zamborlin A, Frusca V, Mapanao AK, Mugnaioli E, et al.
    Copper nano-architecture topical cream for the accelerated recovery of burnt skin
    Nanoscale Advances. 2023; 5(4): 1212-1219. https://doi.org/10.1039/d2na00786j
    DORA PSI
  • Favaretto C, Grundler PV, Talip Z, Landolt S, Sepini L, Köster U, et al.
    161Tb-DOTATOC production using a fully automated disposable cassette system: a first step toward the introduction of 161Tb into the clinic
    Journal of Nuclear Medicine. 2023; 64(7): 1138-1144. https://doi.org/10.2967/jnumed.122.265268
    DORA PSI
  • Müller C, van der Meulen NP, Schibli R
    Opportunities and potential challenges of using terbium-161 for targeted radionuclide therapy in clinics
    European Journal of Nuclear Medicine and Molecular Imaging. 2023; 50: 3181-3184. https://doi.org/10.1007/s00259-023-06316-y
    DORA PSI
  • Sarogni P, Zamborlin A, Mapanao AK, Logghe T, Brancato L, van Zwol E, et al.
    Hyperthermia reduces irradiation-induced tumor repopulation in an in vivo pancreatic carcinoma model
    Advanced biology. 2023; 7(10): 2200229 (9 pp.). https://doi.org/10.1002/adbi.202200229
    DORA PSI
  • Tschan VJ, Busslinger SD, Bernhardt P, Grundler PV, Zeevaart JR, Köster U, et al.
    Albumin-binding and conventional PSMA ligands in combination with 161Tb: biodistribution, dosimetry, and preclinical therapy
    Journal of Nuclear Medicine. 2023; 64(10): 1625-1631. https://doi.org/10.2967/jnumed.123.265524
    DORA PSI
  • Wallimann RH, Schindler P, Hensinger H, Tschan VJ, Busslinger SD, Kneuer R, et al.
    Inductively coupled plasma mass spectrometry - a valid method for the characterization of metal conjugates in view of the development of radiopharmaceuticals
    Molecular Pharmaceutics. 2023; 20(4): 2150-2158. https://doi.org/10.1021/acs.molpharmaceut.2c01092
    DORA PSI
  • Benešová M, Guzik P, Deberle LM, Busslinger SD, Landolt T, Schibli R, et al.
    Design and evaluation of novel albumin-binding folate radioconjugates: systematic approach of varying the linker entities
    Molecular Pharmaceutics. 2022; 19: 963-973. https://doi.org/10.1021/acs.molpharmaceut.1c00932
    DORA PSI
  • Borgna F, Haller S, Monné Rodriguez JM, Ginj M, Grundler PV, Zeevaart JR, et al.
    Combination of terbium-161 with somatostatin receptor antagonists - a potential paradigm shift for the treatment of neuroendocrine neoplasms
    European Journal of Nuclear Medicine and Molecular Imaging. 2022; 49: 1113-1126. https://doi.org/10.1007/s00259-021-05564-0
    DORA PSI
  • Borgna F, Deberle LM, Busslinger SD, Tschan VJ, Walde LM, Becker AE, et al.
    Preclinical investigations to explore the difference between the diastereomers [177Lu]Lu-SibuDAB and [177Lu]Lu-RibuDAB toward prostate cancer therapy
    Molecular Pharmaceutics. 2022; 19(7): 2105-2114. https://doi.org/10.1021/acs.molpharmaceut.1c00994
    DORA PSI
  • Busslinger SD, Tschan VJ, Richard OK, Talip Z, Schibli R, Müller C
    [225Ac]Ac-SibuDAB for targeted alpha therapy of prostate cancer: preclinical evaluation and comparison with [225Ac]Ac-PSMA-617
    Cancers. 2022; 14(22): 5651 (16 pp.). https://doi.org/10.3390/cancers14225651
    DORA PSI
  • Che PP, Mapanao AK, Gregori A, Ermini ML, Zamborlin A, Capula M, et al.
    Biodegradable ultrasmall-in-nano architectures loaded with cisplatin prodrug in combination with ionizing radiation induces DNA damage and apoptosis in pancreatic ductal adenocarcinoma
    Cancers. 2022; 14(12): 3034 (17 pp.). https://doi.org/10.3390/cancers14123034
    DORA PSI
  • Di Liddo R, Verona M, Vaccarin C, Acquasaliente L, Schrenk S, Piccione M, et al.
    Preliminary discovery of small molecule inhibitors of Epidermal Growth Factor Receptor (EGFR) that bind to the extracellular domain
    Cancers. 2022; 14(15): 3647 (22 pp.). https://doi.org/10.3390/cancers14153647
    DORA PSI
  • Franceschinis E, Roverso M, Gabbia D, De Martin S, Brusegan M, Vaccarin C, et al.
    Self-emulsifying formulations to increase the oral bioavailability of 4,6,4′-trimethylangelicin as a possible treatment for cystic fibrosis
    Pharmaceutics. 2022; 14(9): 1806. https://doi.org/10.3390/pharmaceutics14091806
    DORA PSI
  • Hemmingsson J, Svensson J, van der Meulen NP, Müller C, Bernhardt P
    Active bone marrow S-values for the low-energy electron emitter terbium-161 compared to S-values for lutetium-177 and yttrium-90
    EJNMMI Physics. 2022; 9(1): 65 (13 pp.). https://doi.org/10.1186/s40658-022-00495-7
    DORA PSI
  • Miller IS, Khan S, Shiels LP, Das S, O' Farrell AC, Connor K, et al.
    Implementing subtype-specific pre-clinical models of breast cancer to study pre-treatment aspirin effects
    Cancer Medicine. 2022; 11(20): 3820-3836. https://doi.org/10.1002/cam4.4756
    DORA PSI
  • Tschan VJ, Borgna F, Schibli R, Müller C
    Impact of the mouse model and molar amount of injected ligand on the tissue distribution profile of PSMA radioligands
    European Journal of Nuclear Medicine and Molecular Imaging. 2022; 49: 470-480. https://doi.org/10.1007/s00259-021-05446-5
    DORA PSI
  • Tschan VJ, Borgna F, Busslinger SD, Stirn M, Monné Rodriguez JM, Bernhardt P, et al.
    Preclinical investigations using [177Lu]Lu-Ibu-DAB-PSMA toward its clinical translation for radioligand therapy of prostate cancer
    European Journal of Nuclear Medicine and Molecular Imaging. 2022; 49: 3639-3650. https://doi.org/10.1007/s00259-022-05837-2
    DORA PSI
  • Tupini C, Chilin A, Rossi A, De Fino I, Bragonzi A, D’Aversa E, et al.
    New TMA (4,6,4′-trimethyl angelicin) analogues as anti-inflammatory agents in the treatment of cystic fibrosis lung disease
    International Journal of Molecular Sciences. 2022; 23(22): 14483 (20 pp.). https://doi.org/10.3390/ijms232214483
    DORA PSI
  • Vaccarin C, Gabbia D, Franceschinis E, De Martin S, Roverso M, Bogialli S, et al.
    Improved trimethylangelicin analogs for cystic fibrosis: design, synthesis and preliminary screening
    International Journal of Molecular Sciences. 2022; 23(19): 11528 (14 pp.). https://doi.org/10.3390/ijms231911528
    DORA PSI
  • Baum RP, Singh A, Kulkarni HR, Bernhardt P, Rydén T, Schuchardt C, et al.
    First-in-human application of terbium-161: a feasibility study using 161Tb-DOTATOC
    Journal of Nuclear Medicine. 2021; 62(10): 1391-1397. https://doi.org/10.2967/jnumed.120.258376
    DORA PSI
  • Bernhardt P, Svensson J, Hemmingsson J, van der Meulen NP, Zeevaart JR, Konijnenberg MW, et al.
    Dosimetric analysis of the short-ranged particle emitter 161Tb for radionuclide therapy of metastatic prostate cancer
    Cancers. 2021; 13(9): 2011 (13 pp.). https://doi.org/10.3390/cancers13092011
    DORA PSI
  • Borgna F, Barritt P, Grundler PV, Talip Z, Cohrs S, Zeevaart JR, et al.
    Simultaneous visualization of 161Tb-and 177Lu-labeled somatostatin analogues using dual-isotope SPECT imaging
    Pharmaceutics. 2021; 13(4): 536 (13 pp.). https://doi.org/10.3390/pharmaceutics13040536
    DORA PSI
  • Deberle LM, Benešová M, Becker AE, Ratz M, Guzik P, Schibli R, et al.
    Novel synthetic strategies enable the efficient development of folate conjugates for cancer radiotheranostics
    Bioconjugate Chemistry. 2021; 32(8): 1617-1628. https://doi.org/10.1021/acs.bioconjchem.1c00198
    DORA PSI
  • Favaretto C, Talip Z, Borgna F, Grundler PV, Dellepiane G, Sommerhalder A, et al.
    Cyclotron production and radiochemical purification of terbium-155 for SPECT imaging
    EJNMMI Radiopharmacy and Chemistry. 2021; 6: 37 (17 pp.). https://doi.org/10.1186/s41181-021-00153-w
    DORA PSI
  • Guzik P, Fang H-Y, Deberle LM, Benešová M, Cohrs S, Boss SD, et al.
    Identification of a PET radiotracer for imaging of the folate receptor-α: a potential tool to select patients for targeted tumor therapy
    Journal of Nuclear Medicine. 2021; 62(10): 1475-1481. https://doi.org/10.2967/jnumed.120.255760
    DORA PSI
  • Guzik P, Benešová M, Ratz M, Monné Rodríguez JM, Deberle LM, Schibli R, et al.
    Preclinical evaluation of 5-methyltetrahydrofolate-based radioconjugates - new perspectives for folate receptor-targeted radionuclide therapy
    European Journal of Nuclear Medicine and Molecular Imaging. 2021; 48: 972-983. https://doi.org/10.1007/s00259-020-04980-y
    DORA PSI
  • Guzik P, Siwowska K, Fang H-Y, Cohrs S, Bernhardt P, Schibli R, et al.
    Promising potential of [177Lu]Lu-DOTA-folate to enhance tumor response to immunotherapy - a preclinical study using a syngeneic breast cancer model
    European Journal of Nuclear Medicine and Molecular Imaging. 2021; 48: 984-994. https://doi.org/10.1007/s00259-020-05054-9
    DORA PSI
  • Haixia X, Oliveira da Silva de Barros A, do Vale Chaves e Mello F, Sozzi-Guo F, Müller C, Gemini-Piperni S, et al.
    Graphene: insights on biological, radiochemical and ecotoxicological aspects
    Journal of Biomedical Nanotechnology. 2021; 17(1): 131-148. https://doi.org/10.1166/jbn.2021.3006
    DORA PSI
  • Kramer V, Fernández R, Lehnert W, Jiménez-Franco LD, Soza-Ried C, Eppard E, et al.
    Biodistribution and dosimetry of a single dose of albumin-binding ligand [177Lu]Lu-PSMA-ALB-56 in patients with mCRPC
    European Journal of Nuclear Medicine and Molecular Imaging. 2021; 48: 893-903. https://doi.org/10.1007/s00259-020-05022-3
    DORA PSI
  • Lima TVM, Gnesin S, Strobel K, del Sol Pérez M, Roos JE, Müller C, et al.
    Fifty shades of scandium: comparative study of PET capabilities using Sc-43 and Sc-44 with respect to conventional clinical radionuclides
    Diagnostics. 2021; 11(10): 1826 (11 pp.). https://doi.org/10.3390/diagnostics11101826
    DORA PSI
  • Müller C, Schibli R, Bernhardt P, Köster U, van der Meulen NP
    Terbium radionuclides for theranostics
    In: Caplan MJ, ed. Reference module in biomedical sciences. sine loco: Elsevier; 2021:(12 pp.). https://doi.org/10.1016/B978-0-12-822960-6.00076-4
    DORA PSI
  • Talip Z, Borgna F, Müller C, Ulrich J, Duchemin C, Ramos JP, et al.
    Production of mass-separated erbium-169 towards the first preclinical in vitro investigations
    Frontiers in Medicine. 2021; 8: 643175 (11 pp.). https://doi.org/10.3389/fmed.2021.643175
    DORA PSI
  • Borgna F, Deberle LM, Cohrs S, Schibli R, Müller C
    Combined application of albumin-binding [177Lu]Lu-PSMA-ALB-56 and fast-cleared PSMA inhibitors: optimization of the pharmacokinetics
    Molecular Pharmaceutics. 2020; 17(6): 2044-2053. https://doi.org/10.1021/acs.molpharmaceut.0c00199
    DORA PSI
  • Deberle LM, Tschan VJ, Borgna F, Sozzi-Guo F, Bernhardt P, Schibli R, et al.
    Albumin-binding PSMA radioligands: impact of minimal structural changes on the tissue distribution profile
    Molecules. 2020; 25(11): 2542 (16 pp.). https://doi.org/10.3390/molecules25112542
    DORA PSI
  • Deberle LM, Benešová M, Umbricht CA, Borgna F, Büchler M, Zhernosekov K, et al.
    Development of a new class of PSMA radioligands comprising ibuprofen as an albumin-binding entity
    Theranostics. 2020; 10(4): 1678-1693. https://doi.org/10.7150/thno.40482
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  • Durán MT, Juget F, Nedjadi Y, Bochud F, Grundler PV, Gracheva N, et al.
    Determination of 161Tb half-life by three measurement methods
    Applied Radiation and Isotopes. 2020; 159: 109085 (9 pp.). https://doi.org/10.1016/j.apradiso.2020.109085
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  • Gnesin S, Müller J, Burger IA, Meisel A, Siano M, Früh M, et al.
    Radiation dosimetry of 18F-AzaFol: a first in-human use of a folate receptor PET tracer
    EJNMMI Research. 2020; 10(1): 32 (12 pp.). https://doi.org/10.1186/s13550-020-00624-2
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  • Lima TVM, Gnesin S, Nitzsche E, Ortega PG, Müller C, van der Meulen NP
    First phantom-based quantitative assessment of scandium-44 using a commercial PET device
    Frontiers in Physics. 2020; 8: 241 (10 pp.). https://doi.org/10.3389/fphy.2020.00241
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  • Marin I, Rydèn T, Van Essen M, Svensson J, Gracheva N, Köster U, et al.
    Establishment of a clinical SPECT/CT protocol for imaging of 161Tb
    EJNMMI Physics. 2020; 7(1): 45 (16 pp.). https://doi.org/10.1186/s40658-020-00314-x
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  • Müller C, Schibli R, Maurer B
    Can nuclear imaging of activated macrophages with folic acid-based radiotracers serve as a prognostic means to identify COVID-19 patients at risk?
    Pharmaceuticals. 2020; 13(9): 238 (8 pp.). https://doi.org/10.3390/ph13090238
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  • Müller C, Béhé M, Geistlich S, van der Meulen NP, Schibli R
    Targeted radiotherapeutics from 'bench-to-bedside'
    Chimia. 2020; 74(12): 939-945. https://doi.org/10.2533/CHIMIA.2020.939
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  • Nedjadi Y, Juget F, Desorgher L, Durán MT, Bochud F, Müller C, et al.
    Activity standardisation of 161Tb
    Applied Radiation and Isotopes. 2020; 166: 109411 (13 pp.). https://doi.org/10.1016/j.apradiso.2020.109411
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  • Nizou G, Favaretto C, Borgna F, Grundler PV, Saffon-Merceron N, Platas-Iglesias C, et al.
    Expanding the scope of pyclen-picolinate lanthanide chelates to potential theranostic applications
    Inorganic Chemistry. 2020; 59(16): 11736-11748. https://doi.org/10.1021/acs.inorgchem.0c01664
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  • Pietzsch H-J, Mamat C, Müller C, Schibli R
    Single photon emission computed tomography tracer
    In: Schober O, Kiessling F, Debus J, eds. Molecular imaging in oncology. Recent results in cancer research. Cham: Springer Nature; 2020:227-282. https://doi.org/10.1007/978-3-030-42618-7_7
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  • van der Meulen NP, Hasler R, Talip Z, Grundler PV, Favaretto C, Umbricht CA, et al.
    Developments toward the implementation of 44Sc production at a medical cyclotron
    Molecules. 2020; 25(20): 4706 (16 pp.). https://doi.org/10.3390/molecules25204706
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  • Boss SD, Müller C, Siwowska K, Schmid RM, Groehn V, Schibli R, et al.
    Diastereomerically pure 6R- and 6S-3'-aza-2'-18F-fluoro-5-methyltetrahydrofolates show unprecedentedly high uptake in folate receptor-positive KB tumors
    Journal of Nuclear Medicine. 2019; 60(1): 135-141. https://doi.org/10.2967/jnumed.118.213314
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  • Cicone F, Gnesin S, Denoël T, Stora T, van der Meulen NP, Müller C, et al.
    Internal radiation dosimetry of a 152Tb-labeled antibody in tumor-bearing mice
    EJNMMI Research. 2019; 9: 53 (10 pp.). https://doi.org/10.1186/s13550-019-0524-7
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  • Gracheva N, Müller C, Talip Z, Heinitz S, Köster U, Zeevaart JR, et al.
    Production and characterization of no-carrier-added 161Tb as an alternative to the clinically-applied 177Lu for radionuclide therapy
    EJNMMI Radiopharmacy and Chemistry. 2019; 4: 12 (16 pp.). https://doi.org/10.1186/s41181-019-0063-6
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  • Kranzbühler B, Salemi S, Umbricht CA, Deberle LM, Müller C, Burger IA, et al.
    Concentration‐dependent effects of dutasteride on prostate‐specific membrane antigen (PSMA) expression and uptake of 177Lu‐PSMA‐617 in LNCaP cells
    Prostate. 2019; 79(12): 1477-1483. https://doi.org/10.1002/pros.23868
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  • Müller C, De Prado Leal M, Dominietto MD, Umbricht CA, Safai S, Perrin RL, et al.
    Combination of proton therapy and radionuclide therapy in mice: preclinical pilot sudy at the Paul Scherrer Institute
    Pharmaceutics. 2019; 11(9): 450 (13 pp.). https://doi.org/10.3390/pharmaceutics11090450
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  • Müller C, Singh A, Umbricht CA, Kulkarni HR, Johnston K, Benešová M, et al.
    Preclinical investigations and first-in-human application of 152Tb-PSMA-617 for PET/CT imaging of prostate cancer
    EJNMMI Research. 2019; 9(1): 68 (10 pp.). https://doi.org/10.1186/s13550-019-0538-1
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  • Müller C, Umbricht CA, Gracheva N, Tschan VJ, Pellegrini G, Bernhardt P, et al.
    Terbium-161 for PSMA-targeted radionuclide therapy of prostate cancer
    European Journal of Nuclear Medicine and Molecular Imaging. 2019; 46(9): 1919-1930. https://doi.org/10.1007/s00259-019-04345-0
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  • Radford LL, Fernandez S, Beacham R, Sayed RE, Farkas R, Benešová M, et al.
    New 55Co-labeled albumin-binding folate derivatives as potential PET agents for folate receptor imaging
    Pharmaceuticals. 2019; 12(4): 166 (12 pp.). https://doi.org/10.3390/ph12040166
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  • Rupp NJ, Umbricht CA, Pizzuto DA, Lenggenhager D, Töpfer A, Müller J, et al.
    First clinico-pathological evidence of a non PSMA-related uptake mechanism for 68Ga-PSMA-11 in salivary glands
    Journal of Nuclear Medicine. 2019; 60(9): 1270-1276. https://doi.org/10.2967/jnumed.118.222307
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  • Schniering J, Benešová M, Brunner M, Haller S, Cohrs S, Frauenfelder T, et al.
    18F-AzaFol for detection of folate receptor-β positive macrophages in experimental interstitial lung disease - a proof-of-concept study
    Frontiers in Immunology. 2019; 10: 2724 (15 pp.). https://doi.org/10.3389/fimmu.2019.02724
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  • Siwowska K, Guzik P, Domnanich KA, Monné Rodríguez JM, Bernhardt P, Ponsard B, et al.
    Therapeutic potential of 47Sc in comparison to 177Lu and 90Y: preclinical investigations
    Pharmaceutics. 2019; 11(8): 424 (13 pp.). https://doi.org/10.3390/pharmaceutics11080424
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  • Umbricht CA, Köster U, Bernhardt P, Gracheva N, Johnston K, Schibli R, et al.
    Alpha-PET for prostate cancer: preclinical investigation using 149Tb-PSMA-617
    Scientific Reports. 2019; 9: 17800 (10 pp.). https://doi.org/10.1038/s41598-019-54150-w
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  • Zhang J, Singh A, Kulkarni HR, Schuchardt C, Müller D, Wester H-J, et al.
    From bench to bedside—the Bad Berka experience with first-in-human studies
    Seminars in Nuclear Medicine. 2019; 49(5): 422-437. https://doi.org/10.1053/j.semnuclmed.2019.06.002
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  • van der Meulen NP, Hasler R, Blanc A, Farkas R, Benešová M, Talip Z, et al.
    Implementation of a new separation method to produce qualitatively improved 64Cu
    Journal of Labelled Compounds and Radiopharmaceuticals. 2019; 62(8): 460-470. https://doi.org/10.1002/jlcr.3730
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  • Benešová M, Umbricht CA, Schibli R, Müller C
    Albumin-binding PSMA ligands: optimization of the tissue distribution profile
    Molecular Pharmaceutics. 2018; 15(3): 934-946. https://doi.org/10.1021/acs.molpharmaceut.7b00877
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  • Boss SD, Müller C, Siwowska K, Büchel JI, Schmid RM, Groehn V, et al.
    Reduced 18F-folate conjugates as a new class of PET tracers for folate receptor imaging
    Bioconjugate Chemistry. 2018; 29(4): 1119-1130. https://doi.org/10.1021/acs.bioconjchem.7b00775
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  • Kranzbühler B, Salemi S, Umbricht CA, Müller C, Burger IA, Sulser T, et al.
    Pharmacological upregulation of prostate-specific membrane antigen (PSMA) expression in prostate cancer cells
    Prostate. 2018; 78(10): 758-765. https://doi.org/10.1002/pros.23522
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  • Lindenblatt D, Terraneo N, Pellegrini G, Cohrs S, Spycher PR, Vukovic D, et al.
    Combination of lutetium-177 labelled anti-L1CAM antibody chCE7 with the clinically relevant protein kinase inhibitor MK1775: a novel combination against human ovarian carcinoma
    BMC Cancer. 2018; 18: 922 (14 pp.). https://doi.org/10.1186/s12885-018-4836-1
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  • Müller C, Guzik P, Siwowska K, Cohrs S, Schmid RM, Schibli R
    Combining albumin-binding properties and interaction with pemetrexed to improve the tissue distribution of radiofolates
    Molecules. 2018; 23(6): 1465 (12 pp.). https://doi.org/10.3390/molecules23061465
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  • Müller C, Domnanich KA, Umbricht CA, van der Meulen NP
    Scandium and terbium radionuclides for radiotheranostics: current state of development towards clinical application
    British Journal of Radiology. 2018; 91(1091): 20180074 (13 pp.). https://doi.org/10.1259/bjr.20180074
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  • Schniering J, Borgna F, Siwowska K, Benešová M, Cohrs S, Hasler R, et al.
    In vivo labeling of plasma proteins for imaging of enhanced vascular permeability in the lungs
    Molecular Pharmaceutics. 2018; 15(11): 4995-5004. https://doi.org/10.1021/acs.molpharmaceut.8b00606
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  • Schniering J, Benešová M, Brunner M, Haller S, Cohrs S, Frauenfelder T, et al.
    Visualisation of interstitial lung disease by molecular imaging of integrin αvβ3 and somatostatin receptor 2
    Annals of the Rheumatic Diseases. 2018; 78(2): 218-227. https://doi.org/10.1136/annrheumdis-2018-214322
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  • Umbricht CA, Benešová M, Hasler R, Schibli R, van der Meulen NP, Müller C
    Design and preclinical evaluation of an albumin-binding PSMA ligand for 64Cu-based PET imaging
    Molecular Pharmaceutics. 2018; 15(12): 5556-5564. https://doi.org/10.1021/acs.molpharmaceut.8b00712
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  • Umbricht CA, Benešová M, Schibli R, Müller C
    Preclinical development of novel PSMA-targeting radioligands: modulation of albumin-binding properties to improve prostate cancer therapy
    Molecular Pharmaceutics. 2018; 15(6): 2297-2306. https://doi.org/10.1021/acs.molpharmaceut.8b00152
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  • de Visser HM, Korthagen NM, Müller C, Ramakers RM, Krijger GC, Lafeber FPJG, et al.
    Imaging of folate receptor expressing macrophages in the rat groove model of osteoarthritis: using a new DOTA-folate conjugate
    Cartilage. 2018; 9(2): 183-191. https://doi.org/10.1177/1947603517738073
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  • Baum RP, Singh A, Benešová M, Vermeulen C, Gnesin S, Köster U, et al.
    Clinical evaluation of the radiolanthanide terbium-152: first-in-human PET/CT with 152Tb-DOTATOC
    Dalton Transactions. 2017; 46(42): 14638-14646. https://doi.org/10.1039/c7dt01936j
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  • Domnanich KA, Müller C, Benešová M, Dressler R, Haller S, Köster U, et al.
    47Sc as useful β–-emitter for the radiotheragnostic paradigm: a comparative study of feasible production routes
    EJNMMI Radiopharmacy and Chemistry. 2017; 2: 5 (17 pp.). https://doi.org/10.1186/s41181-017-0024-x
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  • Domnanich KA, Eichler R, Müller C, Jordi S, Yakusheva V, Braccini S, et al.
    Production and separation of 43Sc for radiopharmaceutical purposes
    EJNMMI Radiopharmacy and Chemistry. 2017; 2: 14 (17 pp.). https://doi.org/10.1186/s41181-017-0033-9
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  • Honarvar H, Müller C, Cohrs S, Haller S, Westerlund K, Eriksson Karlström A, et al.
    Evaluation of the first 44Sc-labeled Affibody molecule for imaging of HER2-expressing tumors
    Nuclear Medicine and Biology. 2017; 45: 15-21. https://doi.org/10.1016/j.nucmedbio.2016.10.004
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  • Kopka K, Benešová M, Bařinka C, Haberkorn U, Babich J
    Glu-ureido-based inhibitors of prostate-specific membrane antigen: lessons learned during the development of a novel class of low-molecular-weight theranostic radiotracers
    Journal of Nuclear Medicine. 2017; 58(Suppl. 2): 17S-26S. https://doi.org/10.2967/jnumed.116.186775
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  • Müller C, Farkas R, Borgna F, Schmid RM, Benešová M, Schibli R
    Synthesis, radiolabeling, and characterization of plasma protein-binding ligands: potential tools for modulation of the pharmacokinetic properties of (radio)pharmaceuticals
    Bioconjugate Chemistry. 2017; 28(9): 2372-2383. https://doi.org/10.1021/acs.bioconjchem.7b00378
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  • Müller C, van der Meulen NP, Benešová M, Schibli R
    Therapeutic radiometals beyond 177Lu and 90Y: production and application of promising α-particle, β–-particle, and Auger electron emitters
    Journal of Nuclear Medicine. 2017; 58(Suppl. 2): 91S-96S. https://doi.org/10.2967/jnumed.116.186825
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  • Pellegrini G, Siwowska K, Haller S, Antoine D, Schibli R, Kipar A, et al.
    A short-term biological indicator for long-term kidney damage after radionuclide therapy in mice
    Pharmaceuticals. 2017; 10(2): 57 (13 pp.). https://doi.org/10.3390/ph10020057
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  • Singh A, van der Meulen NP, Müller C, Klette I, Kulkarni HR, Türler A, et al.
    First-in-human PET/CT imaging of metastatic neuroendocrine neoplasms with cyclotron-produced 44Sc-DOTATOC: a proof-of-concept study
    Cancer Biotherapy and Radiopharmaceuticals. 2017; 32(4): 124-132. https://doi.org/10.1089/cbr.2016.2173
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  • Siwowska K, Schmid RM, Cohrs S, Schibli R, Müller C
    Folate receptor-positive gynecological cancer cells: in vitro and in vivo characterization
    Pharmaceuticals. 2017; 10(3): 72 (17 pp.). https://doi.org/10.3390/ph10030072
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  • Siwowska K, Haller S, Bortoli F, Benešová M, Groehn V, Bernhardt P, et al.
    Preclinical comparison of albumin-binding radiofolates: impact of linker entities on the in vitro and in vivo properties
    Molecular Pharmaceutics. 2017; 14(2): 523-532. https://doi.org/10.1021/acs.molpharmaceut.6b01010
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  • Umbricht CA, Benešová M, Schmid RM, Türler A, Schibli R, van der Meulen NP, et al.
    44Sc-PSMA-617 for radiotheragnostics in tandem with 177Lu-PSMA-617—preclinical investigations in comparison with 68Ga-PSMA-11 and 68Ga-PSMA-617
    EJNMMI Research. 2017; 7(1): 9 (10 pp.). https://doi.org/10.1186/s13550-017-0257-4
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  • Walser M, Umbricht CA, Fröhli E, Nanni P, Hajnal A
    β-integrin de-phosphorylation by the Density-Enhanced Phosphatase DEP-1 attenuates EGFR signaling in C. elegans
    PLoS Genetics. 2017; 13(1): e1006592 (22 pp.). https://doi.org/10.1371/journal.pgen.1006592
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  • Boss SD, Betzel T, Müller C, Fischer CR, Haller S, Reber J, et al.
    Comparative studies of three pairs of α- and γ-conjugated folic acid derivatives labeled with fluorine-18
    Bioconjugate Chemistry. 2016; 27(1): 74-86. https://doi.org/10.1021/acs.bioconjchem.5b00644
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  • Bunka M, Müller C, Vermeulen C, Haller S, Türler A, Schibli R, et al.
    Imaging quality of 44Sc in comparison with five other PET radionuclides using Derenzo phantoms and preclinical PET
    Applied Radiation and Isotopes. 2016; 110: 129-133. https://doi.org/10.1016/j.apradiso.2016.01.006
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  • Domnanich K, Müller C, Farkas R, Schmid RM, Ponsard B, Schibli R, et al.
    44Sc for labeling of DOTA- and NODAGA-functionalized peptides: preclinical in vitro and in vivo investigations
    EJNMMI Radiopharmacy and Chemistry. 2016; 1: 8 (19 pp.). https://doi.org/10.1186/s41181-016-0013-5
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  • Farkas R, Siwowska K, Ametamey SM, Schibli R, van der Meulen NP, Müller C
    64Cu- and 68Ga-based PET imaging of folate receptor-positive tumors: development and evaluation of an albumin-binding NODAGA−folate
    Molecular Pharmaceutics. 2016; 13(6): 1979-1987. https://doi.org/10.1021/acs.molpharmaceut.6b00143
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  • Haller S, Pellegrini G, Vermeulen C, van der Meulen NP, Köster U, Bernhardt P, et al.
    Contribution of Auger/conversion electrons to renal side effects after radionuclide therapy: preclinical comparison of 161Tb-folate and 177Lu-folate
    EJNMMI Research. 2016; 6(1): 13 (11 pp.). https://doi.org/10.1186/s13550-016-0171-1
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  • Krall N, Pretto F, Mattarella M, Müller C, Neri D
    A 99mTc-labeled ligand of carbonic anhydrase IX selectively targets renal cell carcinoma in vivo
    Journal of Nuclear Medicine. 2016; 57(6): 943-949. https://doi.org/10.2967/jnumed.115.170514
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  • Müller C, Vermeulen C, Köster U, Johnston K, Türler A, Schibli R, et al.
    Alpha-PET with terbium-149: evidence and perspectives for radiotheragnostics
    EJNMMI Radiopharmacy and Chemistry. 2016; 1(1): 5 (5 pp.). https://doi.org/10.1186/s41181-016-0008-2
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  • Müller C, Vermeulen C, Johnston K, Köster U, Schmid R, Türler A, et al.
    Preclinical in vivo application of 152Tb-DOTANOC: a radiolanthanide for PET imaging
    EJNMMI Research. 2016; 6: 35 (10 pp.). https://doi.org/10.1186/s13550-016-0189-4
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  • Baldoni D, Waibel R, Bläuenstein P, Galli F, Iodice V, Signore A, et al.
    Evaluation of a novel Tc-99m labelled vitamin B12 derivative for targeting Escherichia coli and Staphylococcus aureus In Vitro and in an experimental foreign-body infection model
    Molecular Imaging and Biology. 2015; 17(6): 829-837. https://doi.org/10.1007/s11307-015-0832-x
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  • Haller S, Reber J, Brandt S, Bernhardt P, Groehn V, Schibli R, et al.
    Folate receptor-targeted radionuclide therapy: preclinical investigation of anti-tumor effects and potential radionephropathy
    Nuclear Medicine and Biology. 2015; 42(10): 770-779. https://doi.org/10.1016/j.nucmedbio.2015.06.006
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  • Haller S, Ametamey SM, Schibli R, Müller C
    Investigation of the chick embryo as a potential alternative to the mouse for evaluation of radiopharmaceuticals
    Nuclear Medicine and Biology. 2015; 42(3): 226-233. https://doi.org/10.1016/j.nucmedbio.2014.10.010
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  • Siebelt M, Korthagen N, Wei W, Groen H, Bastiaansen-Jenniskens Y, Müller C, et al.
    Triamcinolone acetonide activates an anti-inflammatory and folate receptor-positive macrophage that prevents osteophytosis in vivo
    Arthritis Research and Therapy. 2015; 17(1): 352 (13 pp.). https://doi.org/10.1186/s13075-015-0865-1
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  • Siwowska K, Müller C
    Preclinical development of small-molecular-weight folate-based radioconjugates: a pharmacological perspective
    Quarterly Journal of Nuclear Medicine and Molecular Imaging. 2015; 59(3): 269-286.
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  • van der Meulen NP, Bunka M, Domnanich K, Müller C, Haller S, Vermeulen C, et al.
    Cyclotron production of 44Sc: from bench to bedside
    Nuclear Medicine and Biology. 2015; 42(9): 745-751. https://doi.org/10.1016/j.nucmedbio.2015.05.005
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  • Müller C, Reber J, Haller S, Dorrer H, Bernhardt P, Zhernosekov K, et al.
    Direct in vitro and in vivo comparison of 161Tb and 177Lu using a tumour-targeting folate conjugate
    European Journal of Nuclear Medicine and Molecular Imaging. 2014; 41(3): 476-485. https://doi.org/10.1007/s00259-013-2563-z
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  • Müller C, Reber J, Haller S, Dorrer H, Köster U, Johnston K, et al.
    Folate receptor targeted alpha-therapy using terbium-149
    Pharmaceuticals. 2014; 7(3): 353-365. https://doi.org/10.3390/ph7030353
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  • Müller C, Fischer E, Behe M, Köster U, Dorrer H, Reber J, et al.
    Future prospects for SPECT imaging using the radiolanthanide terbium-155 — production and preclinical evaluation in tumor-bearing mice
    Nuclear Medicine and Biology. 2014; 41(S): e58-e65. https://doi.org/10.1016/j.nucmedbio.2013.11.002
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  • Müller A, Beck K, Rancic Z, Müller C, Fischer CR, Betzel T, et al.
    Imaging aherosclerotic plaque inflammation via folate receptor targeting using a novel 18F-folate radiotracer
    Molecular Imaging and Biology. 2014; 13(2): (11 pp.). https://doi.org/10.2310/7290.2013.00074
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  • Müller C, Bunka M, Haller S, Köster U, Groehn V, Bernhardt P, et al.
    Promising prospects for 44Sc-/47Sc-based theragnostics: application of 47Sc for radionuclide tumor therapy in mice
    Journal of Nuclear Medicine. 2014; 55(10): 1658-1664. https://doi.org/10.2967/jnumed.114.141614
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  • Ocak M, Gillman AG, Bresee J, Zhang L, Vlad AM, Müller C, et al.
    Folate receptor-targeted multimodality imaging of ovarian cancer in a novel syngeneic mouse model
    Molecular Pharmaceutics. 2014; 12(2): 542-553. https://doi.org/10.1021/mp500628g
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  • Sah BR, Schibli R, Waibel R, Von Boehmer L, Bläuenstein P, Nexo E, et al.
    Tumor imaging in patients with advanced tumors using a new 99mTc-radiolabeled vitamin B12 derivative
    Journal of Nuclear Medicine. 2014; 55(1): 43-49. https://doi.org/10.2967/jnumed.113.122499
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  • Siebelt M, van der Windt AE, Groen HC, Sandker M, Waarsing JH, Müller C, et al.
    FK506 protects against articular cartilage collagenous extra-cellular matrix degradation
    Osteoarthritis and Cartilage. 2014; 22(4): 591-600. https://doi.org/10.1016/j.joca.2014.02.003
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  • Siebelt M, Groen HC, Koelewijn SJ, de Blois E, Sandker M, Waarsing JH, et al.
    Increased physical activity severely induces osteoarthritic changes in knee joints with papain induced sulfate-glycosaminoglycan depleted cartilage
    Arthritis Research and Therapy. 2014; 16(1): R32 (12 pp.). https://doi.org/10.1186/ar4461
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  • Siebelt M, Waarsing JH, Groen HC, Müller C, Koelewijn SJ, de Blois E, et al.
    Inhibited osteoclastic bone resorption through alendronate treatment in rats reduces severe osteoarthritis progression
    Bone. 2014; 66: 163-170. https://doi.org/10.1016/j.bone.2014.06.009
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  • Weiss A, Berndsen RH, Dubois M, Müller C, Schibli R, Griffioen AW, et al.
    In vivo anti-tumor activity of the organometallic ruthenium(ii)-arene complex [Ru(η6-p-cymene)Cl2(pta)] (RAPTA-C) in human ovarian and colorectal carcinomas
    Chemical Science. 2014; 5(12): 4742-4748. https://doi.org/10.1039/c4sc01255k
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  • Betzel T, Müller C, Groehn V, Müller A, Reber J, Fischer CR, et al.
    Radiosynthesis and preclinical evaluation of 3′-aza-2′-[18F]fluorofolic acid: a novel PET radiotracer for folate receptor targeting
    Bioconjugate Chemistry. 2013; 24(2): 205-214. https://doi.org/10.1021/bc300483a
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  • Fischer CR, Groehn V, Reber J, Schibli R, Ametamey SM, Müller C
    Improved PET imaging of tumors in mice using a novel 18F-folate conjugate with an albumin-binding entity
    Molecular Imaging and Biology. 2013; 15(6): 649-654. https://doi.org/10.1007/s11307-013-0651-x
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  • Grünberg J, Jeger S, Sarko D, Dennler P, Zimmermann K, Mier W, et al.
    DOTA-functionalized polylysine: a high number of DOTA chelates positively influences the biodistribution of enzymatic conjugated anti-tumor antibody chCE7agl
    PLoS One. 2013; 8(4): e60350 (10 pp.). https://doi.org/10.1371/journal.pone.0060350
    DORA PSI
  • Müller C, Struthers H, Winiger C, Zhernosekov K, Schibli R
    DOTA conjugate with an albumin-binding entity enables the first folic acid-targeted 177Lu-radionuclide tumor therapy in mice
    Journal of Nuclear Medicine. 2013; 54(1): 124-131. https://doi.org/10.2967/jnumed.112.107235
    DORA PSI
  • Müller C
    Folate-based radiotracers for PET imaging - update and perspectives
    Molecules. 2013; 18(5): 5005-5031. https://doi.org/10.3390/molecules18055005
    DORA PSI
  • Müller C, Reber J, Schlup C, Leamon CP, Schibli R
    In vitro and in vivo evaluation of an innocuous drug cocktail to improve the quality of folic acid targeted nuclear imaging in preclinical research
    Molecular Pharmaceutics. 2013; 10(3): 967-974. https://doi.org/10.1021/mp300428p
    DORA PSI
  • Müller C, Bunka M, Reber J, Fischer C, Zhernosekov K, Türler A, et al.
    Promises of cyclotron-produced 44Sc as a diagnostic match for trivalent β--emitters: in vitro and in vivo study of a 44Sc-DOTA-folate conjugate
    Journal of Nuclear Medicine. 2013; 54(12): 2168-2174. https://doi.org/10.2967/jnumed.113.123810
    DORA PSI
  • Müller C, Schibli R
    Prospects in folate receptor-targeted radionuclide therapy
    Frontiers in Oncology. 2013; 3: 249 (10 pp.). https://doi.org/10.3389/fonc.2013.00249
    DORA PSI
  • Reber J, Haller S, Leamon CP, Müller C
    177Lu-EC0800 combined with the antifolate pemetrexed: preclinical pilot study of folate receptor targeted radionuclide tumor therapy
    Molecular Cancer Therapeutics. 2013; 12(11): 2436-2445. https://doi.org/10.1158/1535-7163.MCT-13-0422-T
    DORA PSI
  • Siebelt M, Jahr H, Groen HC, Sandker M, Waarsing JH, Kops N, et al.
    Hsp90 inhibition protects against biomechanically induced osteoarthritis in rats
    Arthritis and Rheumatism. 2013; 65(8): 2102-2112. https://doi.org/10.1002/art.38000
    DORA PSI
  • Weber CJ, Müller S, Safley SA, Gordon KB, Amancha P, Villinger F, et al.
    Expression of functional folate receptors by human parathyroid cells
    Surgery. 2013; 154(6): 1385-1393. https://doi.org/10.1016/j.surg.2013.06.045
    DORA PSI
  • Winkel LCJ, Groen HC, van Thiel BS, Müller C, van der Steen AFW, Wentzel JJ, et al.
    Folate receptor-targeted single-photon emission computed tomography/computed tomography to detect activated macrophages in atherosclerosis: can it distinguish vulnerable from stable atherosclerotic plaques?
    Molecular Imaging. 2013; 13(1): 1-5. https://doi.org/10.2310/7290.2013.00061
    DORA PSI
  • Däpp S, Müller C, Garayoa EG, Bläuenstein P, Maes V, Brans L, et al.
    PEGylation, increasing specific activity and multiple dosing as strategies to improve the risk-benefit profile of targeted radionuclide therapy with 177Lu-DOTA-bombesin analogues
    EJNMMI Research. 2012; 2(1): 24 (12 pp.). https://doi.org/10.1186/2191-219X-2-24
    DORA PSI
  • Fischer E, Grünberg J, Cohrs S, Hohn A, Waldner-Knogler K, Jeger S, et al.
    L1-CAM-targeted antibody therapy and 177Lu-radioimmunotherapy of disseminated ovarian cancer
    International Journal of Cancer. 2012; 130(11): 2715-2721. https://doi.org/10.1002/ijc.26321
    DORA PSI
  • Fischer CR, Müller C, Reber J, Müller A, Krämer SD, Ametamey SM, et al.
    [18F]fluoro-deoxy-glucose folate: a novel PET radiotracer with improved in vivo properties for folate receptor targeting
    Bioconjugate Chemistry. 2012; 23(4): 805-813. https://doi.org/10.1021/bc200660z
    DORA PSI
  • Furger E, Fedosov SN, Launholt Lildballe D, Waibel R, Schibli R, Nexo E, et al.
    Comparison of recombinant human haptocorrin expressed in human embryonic kidney cells and native haptocorrin
    PLoS One. 2012; 7(5): e37421 (9 pp.). https://doi.org/10.1371/journal.pone.0037421
    DORA PSI
  • Krämer SD, Mu L, Müller A, Keller C, Kuznetsova OF, Schweinsberg C, et al.
    5-(2-18F-fluoroethoxy)-L-tryptophan as a substrate of system L transport for tumor imaging by PET
    Journal of Nuclear Medicine. 2012; 53(3): 434-442. https://doi.org/10.2967/jnumed.111.096289
    DORA PSI
  • Müller C, Zhernosekov K, Köster U, Johnston K, Dorrer H, Hohn A, et al.
    A unique matched quadruplet of terbium radioisotopes for PET and SPECT and for α- and β−-radionuclide therapy: an in vivo proof-of-concept study with a new receptor-targeted folate derivative
    Journal of Nuclear Medicine. 2012; 53(12): 1951-1959. https://doi.org/10.2967/jnumed.112.107540
    DORA PSI
  • Müller C
    Folate based radiopharmaceuticals for imaging and therapy of cancer and inflammation
    Current Pharmaceutical Design. 2012; 18(8): 1058-1083. https://doi.org/10.2174/138161212799315777
    DORA PSI
  • Reber J, Struthers H, Betzel T, Hohn A, Schibli R, Müller C
    Radioiodinated folic acid conjugates: evaluation of a valuable concept to improve tumor-to-background contrast
    Molecular Pharmaceutics. 2012; 9(5): 1213-1221. https://doi.org/10.1021/mp200511t
    DORA PSI
  • Dias CR, Jeger S, Osso JAJ, Müller C, De Pasquale C, Hohn A, et al.
    Radiolabeling of rituximab with 188Re and 99mTc using the tricarbonyl technology
    Nuclear Medicine and Biology. 2011; 38(1): 19-28. https://doi.org/10.1016/j.nucmedbio.2010.05.010
    DORA PSI
  • Däpp S, Garayoa EG, Maes V, Brans L, Tourwé DA, Müller C, et al.
    PEGylation of 99mTc-labeled bombesin analogues improves their pharmacokinetic properties
    Nuclear Medicine and Biology. 2011; 38(7): 997-1009. https://doi.org/10.1016/j.nucmedbio.2011.02.014
    DORA PSI
  • Groehn V, Moser R, Ross TL, Betzel T, Müller C, Schibli R, et al.
    Synthesis of precursors for 18F-labeling of folic acid for PET application
    Synthesis. 2011; 2011(22): 3639-3648. https://doi.org/10.1055/s-0030-1260247
    DORA PSI
  • Müller C, Schibli R
    Folic acid conjugates for nuclear imaging of folate receptor-positive cancer
    Journal of Nuclear Medicine. 2011; 52(1): 1-4. https://doi.org/10.2967/jnumed.110.076018
    DORA PSI
  • Müller C, Vlahov IR, Santhapuram HKR, Leamon CP, Schibli R
    Tumor targeting using 67Ga-DOTA-Bz-folate — investigations of methods to improve the tissue distribution of radiofolates
    Nuclear Medicine and Biology. 2011; 38(5): 715-723. https://doi.org/10.1016/j.nucmedbio.2010.12.013
    DORA PSI
  • Piscaer TM, Müller C, Mindt TL, Lubberts E, Verhaar JAN, Krenning EP, et al.
    Imaging of activated macrophages in experimental osteoarthritis using folate-targeted animal single-photon-emission computed tomography/computed tomography
    Arthritis and Rheumatism. 2011; 63(7): 1898-1907. https://doi.org/10.1002/art.30363
    DORA PSI
  • Müller C, Reddy JA, Leamon CP, Schibli R
    Effects of the antifolates pemetrexed and CB3717 on the tissue distribution of 99mTc-EC20 in xenografted and syngeneic tumor-bearing mice
    Molecular Pharmaceutics. 2010; 7(2): 597-604. https://doi.org/10.1021/mp900296k
    DORA PSI
  • Ross TL, Honer M, Müller C, Groehn V, Schibli R, Ametamey SM
    A new 18F-labeled folic acid derivative with improved properties for the PET imaging of folate receptor-positive tumors
    Journal of Nuclear Medicine. 2010; 51(11): 1756-1762. https://doi.org/10.2967/jnumed.110.079756
    DORA PSI
  • Zahnd C, Kawe M, Stumpp MT, De Pasquale C, Tamaskovic R, Nagy-Davidescu G, et al.
    Efficient tumor targeting with high-affinity designed ankyrin repeat proteins: effects of affinity and molecular size
    Cancer Research. 2010; 70(4): 1595-1605. https://doi.org/10.1158/0008-5472.CAN-09-2724
    DORA PSI
  • Harris DA, Pellikka R, Gasser O, Blaeuenstein P, Waibel R, Schubiger PA, et al.
    In-line radiolabeling: a novel continuous-flow system for commercial-scale protein labeling
    Journal of Nuclear Medicine. 2009; 50(7): 1178-1186. https://doi.org/10.2967/jnumed.108.056812
    DORA PSI
  • Mindt TL, Müller C, Stuker F, Salazar J-F, Hohn A, Mueggler T, et al.
    A “click chemistry” approach to the efficient synthesis of multiple imaging probes derived from a single precursor
    Bioconjugate Chemistry. 2009; 20(10): 1940-1949. https://doi.org/10.1021/bc900276b
    DORA PSI
  • Müller C, Mindt TL, de Jong M, Schibli R
    Evaluation of a novel radiofolate in tumour-bearing mice: promising prospects for folate-based radionuclide therapy
    European Journal of Nuclear Medicine and Molecular Imaging. 2009; 36(6): 938-946. https://doi.org/10.1007/s00259-008-1058-9
    DORA PSI
  • Sparr C, Michel U, Marti RE, Müller C, Schibli R, Moser R, et al.
    Synthesis of a novel γ-folic acid-Nτ-histidine conjugate suitable for labeling with 99mTc and 188Re
    Synthesis. 2009;(05): 787-792. https://doi.org/10.1055/s-0028-1083345
    DORA PSI
  • Struthers H, Hagenbach A, Abram U, Schibli R
    Organometallic [Re(CO)3]+ and [Re(CO)2(NO)]2+ labeled substrates for human thvmidine kinase 1
    Inorganic Chemistry. 2009; 48(12): 5154-5163. https://doi.org/10.1021/ic9000126
    DORA PSI
  • Desbouis D, Struthers H, Spiwok V, Küster T, Schibli R
    Synthesis, in vitro, and in silico evaluation of organometallic technetium and rhenium thymidine complexes with retained substrate activity toward human thymidine kinase type 1
    Journal of Medicinal Chemistry. 2008; 51(21): 6689-6698. https://doi.org/10.1021/jm800530p
    DORA PSI
  • Hohn A, Zimmermann K, Schaub E, Hirzel W, Schubiger PA, Schibli R
    Production and separation of "non-standard" PET nuclides at a large cyclotron facility: the experiences at the Paul Scherrer Institute in Switzerland
    Quarterly Journal of Nuclear Medicine and Molecular Imaging. 2008; 52(2): 145-150.
    DORA PSI
  • Mindt TL, Müller C, Melis M, de Jong M, Schibli R
    "Click-to-chelate": in vitro and in vivo comparison of a 99mTc(CO)3-labeled N(τ)-histidine folate derivative with its isostructural, clicked 1,2,3-triazole analogue
    Bioconjugate Chemistry. 2008; 19(8): 1689-1695. https://doi.org/10.1021/bc800183r
    DORA PSI
  • Struthers H, Spingler B, Mindt TL, Schibli R
    "Click-to-chelate": design and incorporation of triazole-containing metal-chelating systems into biomolecules of diagnostic and therapeutic interest
    Chemistry: A European Journal. 2008; 14(20): 6173-6183. https://doi.org/10.1002/chem.200702024
    DORA PSI
  • Waibel R, Treichler H, Schaefer NG, van Staveren DR, Mundwiler S, Kunze S, et al.
    New derivatives of vitamin B12 show preferential targeting of tumors
    Cancer Research. 2008; 68(8): 2904-2911. https://doi.org/10.1158/0008-5472.CAN-07-6771
    DORA PSI
  • Desbouis D, Schubiger PA, Schibli R
    Synthesis of tricarbonyl rhenium and technetium complexes of a 5′-carboxamide 5-ethyl-2′-deoxyuridine for selective inhibition of herpes simplex virus thymidine kinase 1
    Journal of Organometallic Chemistry. 2007; 692(6): 1340-1347. https://doi.org/10.1016/j.jorganchem.2006.10.011
    DORA PSI
  • Mindt T, Struthers H, Garcia-Garayoa E, Desbouis D, Schibli R
    Strategies for the development of novel tumor targeting technetium and rhenium radiopharmaceuticals
    Chimia. 2007; 61(11): 725-731. https://doi.org/10.2533/chimia.2007.725
    DORA PSI
  • Müller C, Schubiger PA, Schibli R
    Isostructural folate conjugates radiolabeled with the matched pair 99mTc/188Re: a potential strategy for diagnosis and therapy of folate receptor-positive tumors
    Nuclear Medicine and Biology. 2007; 34(6): 595-601. https://doi.org/10.1016/j.nucmedbio.2007.05.011
    DORA PSI
  • Stichelberger M, Desbouis D, Spiwok V, Scapozza L, Schubiger PA, Schibli R
    Synthesis, in vitro and in silico assessment of organometallic rhenium(I) and technetium(I) thymidine complexes
    Journal of Organometallic Chemistry. 2007; 692(6): 1255-1264. https://doi.org/10.1016/j.jorganchem.2006.08.101
    DORA PSI
  • Zehnder-Fjällman AHM, Marty C, Halin C, Hohn A, Schibli R, Ballmer-Hofer K, et al.
    Evaluation of anti-VEGFR-3 specific scFv antibodies as potential therapeutic and diagnostic tools for tumor lymph-angiogenesis
    Oncology Reports. 2007; 18(4): 933-941. https://doi.org/10.3892/or.18.4.933
    DORA PSI
  • Bettio A, Honer M, Müller C, Brühlmeier M, Müller U, Schibli R, et al.
    Synthesis and preclinical evaluation of a folic acid derivative labeled with 18F for PET imaging of folate receptor-positive tumors
    Journal of Nuclear Medicine. 2006; 47(7): 1153-1160. http://jnm.snmjournals.org/content/47/7/1153.long.
    DORA PSI
  • García-Garayoa E, Maes V, Bläuenstein P, Blanc A, Hohn A, Tourwé D, et al.
    Double-stabilized neurotensin analogues as potential radiopharmaceuticals for NTR-positive tumors
    Nuclear Medicine and Biology. 2006; 33(4): 495-503. https://doi.org/10.1016/j.nucmedbio.2006.01.007
    DORA PSI
  • Mindt TL, Struthers H, Brans L, Anguelov T, Schweinsberg C, Maes V, et al.
    "Click to chelate": synthesis and installation of metal chelates into biomolecules in a single step
    Journal of the American Chemical Society. 2006; 128(47): 15096-15097. https://doi.org/10.1021/ja066779f
    DORA PSI
  • Müller C, Brühlmeier M, Schubiger PA, Schibli R
    Effects of antifolate drugs on the cellular uptake of radiofolates in vitro and in vivo
    Journal of Nuclear Medicine. 2006; 47(12): 2057-2064. http://jnm.snmjournals.org/content/47/12/2057.long.
    DORA PSI
  • Müller C, Schubiger PA, Schibli R
    In vitro and in vivo targeting of different folate receptor-positive cancer cell lines with a novel 99mTc-radiofolate tracer
    European Journal of Nuclear Medicine and Molecular Imaging. 2006; 33(10): 1162-1170. https://doi.org/10.1007/s00259-006-0118-2
    DORA PSI
  • Müller C, Hohn A, Schubiger PA, Schibli R
    Preclinical evaluation of novel organometallic 99mTc-folate and 99mTc-pteroate radiotracers for folate receptor-positive tumour targeting
    European Journal of Nuclear Medicine and Molecular Imaging. 2006; 33(9): 1007-1016. https://doi.org/10.1007/s00259-006-0111-9
    DORA PSI
  • Müller C, Schubiger PA, Schibli R
    Synthesis and in vitro/in vivo evaluation of novel 99mTc(CO)3-folates
    Bioconjugate Chemistry. 2006; 17(3): 797-806. https://doi.org/10.1021/bc050323q
    DORA PSI