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Center for Radiopharmaceutical Sciences (CRS)

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Nuclide Chemistry

Background

in preparation

Research Interests

The research of our group is dedicated to the design and evaluation of small-molecular-weight tumor targeting radioligands for theragnostic application, among those 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. 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

Research Projects

Novel Tumor-Targeting Agents - Ligand Design and Optimization

Our research group has developed a large number of folic acid conjugates for labeling with diagnostic and therapeutic radionuclides. 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.

 

Application and Investigation of Non-Standard (Exotic) Radionuclides

A major project of the group refers to the application and investigation of non-standard (exotic) radionuclides, which are developed and produced by the Radionuclide Development group (headed by Dr. Nicholas van der Meulen).

https://www.psi.ch/de/zrw/development-of-radionuclides

In this regard, we are 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 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.

Currently, several projects are being performed with radioisotopes of scandium and terbium. Recently, new projects have been initiated with regard to more in-depth studies using other exotic radionuclides.

Terbium radioisotopes

 

Combination Therapies

In this project, we focus on the combined application of targeted radionuclide therapy with other therapy modalities. Over the last years, we have been investigating the radiosensitizing effects of chemotherapeutic agents (e.g. pemetrexed). More recently, we are also investigating the effect of radiation to enhance the tumor response to immunotherapies.

Clinical Translation

The long-term goal of our research is the clinical translation of new radiotheragnostic concepts. In this regard, we have been collaborating with nuclear medicine physicians and oncologists who performed a clinical study with 18F-AzaFol, a PET agent for imaging folate receptor-positive tumors (NCT03242993). Currently, several projects are on-going with regard to first-in-man applications of novel tumor targeting agents and radionuclides, respectively.

Prizes and Awards

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"

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).

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*

August-Abegg-Fonds Prize (Doktorandentag, ETH Zurich, 2018)

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

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.

Links

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)

Publications

  • 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, 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
    DORA PSI
  • 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
    DORA PSI
  • 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
    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. 2020. 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. 2020: (11 pp.). https://doi.org/10.1007/s00259-020-05054-9
    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. 2020: (11 pp.). https://doi.org/10.1007/s00259-020-05022-3
    DORA PSI
  • 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
    DORA PSI
  • 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
    DORA PSI
  • 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
    DORA PSI
  • 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
    DORA PSI
  • 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
    DORA PSI
  • 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
    DORA PSI
  • 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; 2020:227-282. https://doi.org/10.1007/978-3-030-42618-7_7
    DORA PSI
  • Tschan VJ, Deberle LM, 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
  • 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
    DORA PSI
  • 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
    DORA PSI
  • 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
    DORA PSI
  • 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
    DORA PSI
  • 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
    DORA PSI
  • 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
    DORA PSI
  • 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
    DORA PSI
  • 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
    DORA PSI
  • 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
    DORA PSI
  • 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
    DORA PSI
  • 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
    DORA PSI
  • 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
    DORA PSI
  • 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
    DORA PSI
  • 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
    DORA PSI
  • 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
    DORA PSI
  • 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
    DORA PSI
  • 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
    DORA PSI
  • 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
    DORA PSI
  • 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
    DORA PSI
  • 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
    DORA PSI
  • 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
    DORA PSI
  • 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
    DORA PSI
  • 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
    DORA PSI
  • 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
    DORA PSI
  • 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
    DORA PSI
  • 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
    DORA PSI
  • 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
    DORA PSI
  • 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
    DORA PSI
  • 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
    DORA PSI
  • 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
    DORA PSI
  • 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
    DORA PSI
  • 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(9(Suppl. 2): 91S-96S. https://doi.org/10.2967/jnumed.116.186825
    DORA PSI
  • 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
    DORA PSI
  • 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
    DORA PSI
  • 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
    DORA PSI
  • 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
    DORA PSI
  • 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
    DORA PSI
  • 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
    DORA PSI
  • 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
    DORA PSI
  • 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
    DORA PSI
  • 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
    DORA PSI
  • 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
    DORA PSI
  • 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
    DORA PSI
  • 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
    DORA PSI
  • 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
    DORA PSI
  • 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
    DORA PSI
  • 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
    DORA PSI
  • 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
    DORA PSI
  • 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.
    DORA PSI
  • 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
    DORA PSI
  • 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
    DORA PSI
  • 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
    DORA PSI
  • 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
    DORA PSI
  • 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
    DORA PSI
  • 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
    DORA PSI
  • 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
    DORA PSI
  • 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
    DORA PSI
  • 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
    DORA PSI
  • 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
    DORA PSI
  • 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
    DORA PSI
  • 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
    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 177 Lu-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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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

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OIPA/101
5232 Villigen PSI
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