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Advanced radiochemical methods for multi-modal imaging with nanomedicines

Applicant Holland Jason
Number 163683
Funding scheme SNSF Professorships
Research institution Institut für Chemie Universität Zürich
Institution of higher education University of Zurich - ZH
Main discipline Inorganic Chemistry
Start/End 01.04.2016 - 31.03.2020
Approved amount 1'589'999.00
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All Disciplines (2)

Discipline
Inorganic Chemistry
Cancer

Keywords (12)

Nanomedicine; Computational chemistry; Cancer; Imaging; PET/MRI; Radiochemistry; Metal complexes; Fluorine; Synthesis; Oncogenic signaling; Coordination chemistry; Ligand

Lay Summary (German)

Lead
Nanomedizin ist die klinische Anwendung der Nanotechnologie für Diagnose oder Behandlung von Krankheiten. Im Zusammenhang mit bildgebenden Verfahren ist Nanomedizin eine attraktive Platform für die Entwicklung einer nächsten Generation von zielgerichteten molekularen Sonden, welche mit fortschrittlichen Detektionsmethoden wie PET und MRI nachgewiesen werden können. Zusammen mit neuartigen PET/MRI Kameras kann Nanomedizin dazu beitragen, unser Verständnis über die biochemischen Veränderungen, welche zum Beispiel in Krebs stattfinden, voranzutreiben.
Lay summary

Inhalt und Ziel des Forschungsprojekts

Im Rahmen dieser interdisziplinären SNF Professur sollen neue Möglichkeiten erforscht werden, um bildgebende molekulare Sonden herzustellen. Das Hauptziel ist, eine breite Palette synthetischer Methoden zu entwickeln, mit welchen radioaktive Elemente in wichtige Klassen von Molekülen eingeführt werden können. Zum Beispiel sind das Antikörper, Proteine, Peptide etc, die sich in Krebszellen anreichern und deshalb hervorragende Sonden für die Krebsdiagnose darstellen. Neben diesen fundamentalen chemischen Weiterentwicklungen ist es auch ein langfristiges Ziel, ganz spezifische PET/MRI-Sonden zu entwickeln, welche gezielt Veränderungen in wichtigen biochemischen Mustern von Krebserkrankungen erkennen, wie sie vor, während und nach Behandlung stattfinden.

Wissenschaftlicher und gesellschaftlicher Kontext des Forschungsprojekts

Unsere Arbeit wird wichtige Beiträge in den Gebieten der Chemie, Radiochemie, Bildgebung und Onkologie hervorbringen. Neuartige chemische und radiochemische Methoden werden dazu beitragen, molekulare Sonden für die Bildgebung zu entwickeln, welche wiederum unser Verständnis über die molekularen Grundlagen von Krebserkrankungen vertiefen werden. Die Ergebnisse des Projektes werden in die Klinik transferiert, was letztlich zu einem direkten Vorteil für Krebspatienten führt.

Direct link to Lay Summary Last update: 21.04.2016

Responsible applicant and co-applicants

Employees

Publications

Publication
Light‐Activated Protein Conjugation and 89 Zr‐Radiolabelling with Water‐Soluble Desferrioxamine Derivatives
Guillou Amaury, Earley Daniel, Holland Jason P. (2020), Light‐Activated Protein Conjugation and 89 Zr‐Radiolabelling with Water‐Soluble Desferrioxamine Derivatives, in Chemistry - A European Journal.
Light-induced radiosynthesis of 89ZrDFO-azepin-onartuzumab for imaging the hepatocyte growth factor receptor
Klingler Simon, Fay Rachael, Holland Jason P. (2020), Light-induced radiosynthesis of 89ZrDFO-azepin-onartuzumab for imaging the hepatocyte growth factor receptor, in The Journal of Nuclear Medicine.
Photochemical Reactions in the Synthesis of Protein–Drug Conjugates
Holland Jason P., Gut Melanie, Klingler Simon, Fay Rachael, Guillou Amaury (2020), Photochemical Reactions in the Synthesis of Protein–Drug Conjugates, in Chemistry {\textendash} A European Journal, 26(1), 33-48.
PhotoTag: Photoactivatable Fluorophores for Protein Labeling
Fay Rachael, Linden Anthony, Holland Jason P. (2020), PhotoTag: Photoactivatable Fluorophores for Protein Labeling, in Organic Letters.
Predicting the Thermodynamic Stability of Zirconium Radiotracers
Holland Jason P. (2020), Predicting the Thermodynamic Stability of Zirconium Radiotracers, in Inorganic Chemistry, 59, 2070-2082.
Revisiting the Radiosynthesis of [18F]FPEB and Preliminary PET Imaging in a Mouse Model of Alzheimer’s Disease
Varlow Cassis, Murrell Emily, Holland Jason P., Kassenbrock Alina, Shannon Whitney, Liang Steven H., Vasdev Neil, Stephenson Nickeisha (2020), Revisiting the Radiosynthesis of [18F]FPEB and Preliminary PET Imaging in a Mouse Model of Alzheimer’s Disease, in Molecules, 25(4), 982-982.
Simultaneous Photoradiochemical Labeling of Antibodies for Immuno-Positron Emission Tomography
Patra Malay, Klingler Simon, Eichenberger Larissa S., Holland Jason P. (2019), Simultaneous Photoradiochemical Labeling of Antibodies for Immuno-Positron Emission Tomography, in iScience, 13, 416-431.
endo-Hydroxamic Acid Monomers for the Assembly of a Suite of Non-native Dimeric Macrocyclic Siderophores Using Metal-Templated Synthesis
Brown Christopher J. M., Gotsbacher Michael P., Holland Jason P., Codd Rachel (2019), endo-Hydroxamic Acid Monomers for the Assembly of a Suite of Non-native Dimeric Macrocyclic Siderophores Using Metal-Templated Synthesis, in Inorganic Chemistry, 58, 13591-13603.
Frontispiece: Photochemical Conjugation and One-Pot Radiolabelling of Antibodies for Immuno-PET
Patra Malay, Eichenberger Larissa S., Fischer Gregor, Holland Jason P. (2019), Frontispiece: Photochemical Conjugation and One-Pot Radiolabelling of Antibodies for Immuno-PET, in Angewandte Chemie International Edition, 58, 1928-1933.
Frontispiz: Photochemische Konjugation und Eintopfradiomarkierung von Antikörpern für Immun-PET
Patra Malay, Eichenberger Larissa S., Fischer Gregor, Holland Jason P. (2019), Frontispiz: Photochemische Konjugation und Eintopfradiomarkierung von Antikörpern für Immun-PET, in Angewandte Chemie, 131, 1946-1951.
Multi-functionalised graphene nanoflakes as tumour-targeting theranostic drug-delivery vehicles
Lamb Jennifer, Fischer Eliane, Rosillo-Lopez Martin, Salzmann Christoph G., Holland Jason P. (2019), Multi-functionalised graphene nanoflakes as tumour-targeting theranostic drug-delivery vehicles, in Chemical Science, 10, 8880-8888.
Photoactive chelates for radiolabelling proteins
Eichenberger Larissa S., Patra Malay, Holland Jason P. (2019), Photoactive chelates for radiolabelling proteins, in Chemical Communications, 55, 2257-2260.
Photochemical Conjugation and One-Pot Radiolabelling of Antibodies for Immuno-PET
Patra Malay, Eichenberger Larissa S., Fischer Gregor, Holland Jason P. (2019), Photochemical Conjugation and One-Pot Radiolabelling of Antibodies for Immuno-PET, in Angewandte Chemie International Edition, 58, 1928-1933.
Photochemische Konjugation und Eintopfradiomarkierung von Antikörpern für Immun-PET
Patra Malay, Eichenberger Larissa S., Fischer Gregor, Holland Jason P. (2019), Photochemische Konjugation und Eintopfradiomarkierung von Antikörpern für Immun-PET, in Angewandte Chemie, 131, 1946-1951.
Photoradiosynthesis of 68Ga-Labeled HBED-CC-Azepin-MetMAb for Immuno-PET of c-MET Receptors
Fay Rachael, Gut Melanie, Holland Jason P. (2019), Photoradiosynthesis of 68Ga-Labeled HBED-CC-Azepin-MetMAb for Immuno-PET of c-MET Receptors, in Bioconjugate Chemistry, 30, 1814-1820.
Radiochemistry of Seldom-used Radionuclides in Nuclear Medicine
Holland Jason P. (2019), Radiochemistry of Seldom-used Radionuclides in Nuclear Medicine, in Zeglis Brian M., Lewis Jason S., Windhorst Albert (ed.), Springer, New York, 1-651.
Synthesis and Photochemical Studies on Gallium and Indium Complexes of DTPA-PEG3-ArN3 for Radiolabeling Antibodies
Gut Melanie, Holland Jason P. (2019), Synthesis and Photochemical Studies on Gallium and Indium Complexes of DTPA-PEG3-ArN3 for Radiolabeling Antibodies, in Inorganic Chemistry, 58(18), 12302-12310.
Two is better than one: difunctional high-affinity PSMA probes based on a [CpM(CO)3] (M = Re/99mTc) scaffold
Frei Angelo, Fischer Eliane, Childs Bradley Covington, Holland Jason P., Alberto Roger (2019), Two is better than one: difunctional high-affinity PSMA probes based on a [CpM(CO)3] (M = Re/99mTc) scaffold, in Dalton Transactions, 48, 14600-14605.
Optimized synthesis and indium complex formation with the bifunctional chelator NODIA-Me
Weinmann Christian, Holland Jason P., Läppchen Tilman, Scherer Harald, Maus Stephan, Stemler Tobias, Bohnenberger Hendrik, Ezziddin Samer, Kurz Philipp, Bartholomä Mark D. (2018), Optimized synthesis and indium complex formation with the bifunctional chelator NODIA-Me, in Organic & Biomolecular Chemistry, 16(40), 7503-7512.
Advanced methods for radiolabelling multi-modality nanomedicines for SPECT/MRI and PET/MRI
Lamb Jennifer, Holland Jason P. (2018), Advanced methods for radiolabelling multi-modality nanomedicines for SPECT/MRI and PET/MRI, in Journal of Nuclear Medicine, 59, 382-389.
Antibody-based radiopharmaceuticals for imaging and therapy
Holland Jason P. (2018), Antibody-based radiopharmaceuticals for imaging and therapy, in Journal of Labelled Compounds and Radiopharmaceuticals, 61, 610-610.
Chemical aspects of metal ion chelation in the synthesis and application antibody-based radiotracers
Boros Eszter, Holland Jason P. (2018), Chemical aspects of metal ion chelation in the synthesis and application antibody-based radiotracers, in Journal of Labelled Compounds and Radiopharmaceuticals, 61, 652-671.
Chemical aspects of metal ion chelation in the synthesis and application antibody‐based radiotracers
Boros Eszter, Holland Jason P. (2018), Chemical aspects of metal ion chelation in the synthesis and application antibody‐based radiotracers, in Journal of Labelled Compounds and Radiopharmaceuticals, 1-20.
Chemical Kinetics of Radiolabelling Reactions
Holland Jason P. (2018), Chemical Kinetics of Radiolabelling Reactions, in Chemistry - A European Journal, 24, 16472-16483.
Frontispiece: Chemical Kinetics of Radiolabelling Reactions
Holland Jason P. (2018), Frontispiece: Chemical Kinetics of Radiolabelling Reactions, in Chemistry - A European Journal, 24, 16472-16483.
In vitro and in vivo evaluation of the bifunctional chelator NODIA-Me in combination with a prostate specific membrane antigen targeting vector
Läppchen Tilman, Kiefer Yvonne, Holland Jason P., Bartholomä Mark (2018), In vitro and in vivo evaluation of the bifunctional chelator NODIA-Me in combination with a prostate specific membrane antigen targeting vector, in Nuclear Medicine and Biology, 60, 45-54.
Preparation and preclinical evaluation of a 68Ga-labelled c(RGDfK) conjugate comprising the bifunctional chelator NODIA-Me
Läppchen Tilman, Kiefer Yvonne, Holland Jason P., Bartholomä Mark (2018), Preparation and preclinical evaluation of a 68Ga-labelled c(RGDfK) conjugate comprising the bifunctional chelator NODIA-Me, in European Journal of Nuclear Medicine and Molecular Imaging: Radiopharmacy and Chemistry, 3(6), 1-11.
Recent applications of a single quadrupole mass spectrometer in PET radiochemistry
Collier Thomas L., Dahl Kenneth, Stephenson Nickeisha A., Holland Jason P., Riley Adam, Liang Steven H., Vasdev Neil (2018), Recent applications of a single quadrupole mass spectrometer in PET radiochemistry, in Journal of Fluorine Chemistry, 210, 46-55.
Gallium complexation, stability and bioconjugation of TACN derived chelators with azaheterocyclic arms
Schmidtke Alexander, Läppchen Tilman, Weinmann Christian, Bier-Schorr Lorenz, Keller Manfred, Kiefer Yvonne, Holland Jason P., Bartholomä Mark D. (2017), Gallium complexation, stability and bioconjugation of TACN derived chelators with azaheterocyclic arms, in Inorganic Chemistry, 56(15), 9097-9110.
Radiochemistry and PET imaging of 68Ga-desferrioxamine radiotracers targeting prostate-specific membrane
Gourni Eleni, Del Pozzo Luigi, Bartholomä Mark, Kiefer Yvonne, Meyer Philipp T., Maecke Helmut R., Holland Jason P. (2017), Radiochemistry and PET imaging of 68Ga-desferrioxamine radiotracers targeting prostate-specific membrane, in Molecular Imaging, 16, 1-11.
The role of molecular imaging in personalised healthcare
Holland Jason P. (2016), The role of molecular imaging in personalised healthcare, in Chimia, 70(11), 787-795.
The impact of emerging bioconjugation chemistries on radiopharmaceuticals
FayRachael, HollandJason, The impact of emerging bioconjugation chemistries on radiopharmaceuticals, in Journal of Nuclear Medicine.

Collaboration

Group / person Country
Types of collaboration
Dr Eszter Boros, Stony Brook University, New York United States of America (North America)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
Prof. Ramon Mangues Bafalluy / Grup d'Oncogènesi i Antitumorals Spain (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Research Infrastructure
- Exchange of personnel
Prof. Rachel Codd, University of Sydney, Pharmacy Australia (Oceania)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
Prof. Philipp Kaufmann, Head of Nuclear Medicine, University Hospital Zurich Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
Prof. Bernhard Spingler, Department of Chemistry, University of Zurich Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Research Infrastructure
Dr. Mark Bartholomä, Department of Nuclear Medicine, University Hospital Freiburg Germany (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
Prof. Roger Alberto University of Zurich, Chemistry Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Research Infrastructure
Prof. Andreas Plückthun / Dr. Jonas Schäfer, University of Zurich / Biochemistry Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Research Infrastructure

Scientific events

Active participation

Title Type of contribution Title of article or contribution Date Place Persons involved
Departmental Seminars - KU Leuven Individual talk Radiochemistry in a Flash 12.03.2020 Leuven, Belgium Holland Jason;
International Conference on Biological Inorganic Chemistry (ICBIC) Poster Synthesis of targeted supramolecular radiotracers by cooperative capture 12.08.2019 Interlaken, Switzerland Holland Jason;
International Conference on Biological Inorganic Chemistry (ICBIC) Poster Multi-functionalised graphene nanoflakes as tumour-targeted theranostic agents 12.08.2019 Interlaken, Switzerland Lamb Jennifer; Holland Jason;
International Conference on Biological Inorganic Chemistry (ICBIC) Talk given at a conference Radiochemistry in a flash: applications of photochemistry in radiotracer design 12.08.2019 Interlaken, Switzerland Earley Daniel Francis; Holland Jason; Guillou Amaury Hervé; Lamb Jennifer; Esteban Flores Jose;
International Conference on Biological Inorganic Chemistry (ICBIC) Poster 89ZrDFO-azepin-MetMAb for imaging c-MET expression in gastric cancer’ at the ICBIC Conference in Interlaken 12.08.2019 Interlaken, Switzerland Holland Jason;
International Conference on Biological Inorganic Chemistry (ICBIC) Talk given at a conference Assembly of non-native dimeric macrocyclic siderophores using dual approaches in metal-mediated synthesis 12.08.2019 Interlaken, Switzerland Guillou Amaury Hervé; Earley Daniel Francis; Holland Jason;
International Conference on Biological Inorganic Chemistry (ICBIC) Poster Synthesis of HBED-CC-ArN3 and immunoPET of c-MET using photoradiolabelled [68Ga]GaHBED-CC-MetMAb 12.08.2019 Interlaken, Switzerland Holland Jason;
Special Symposium on Radiopharmaceutical Sciences - celebrating Jon Dilworth's 75th Birthday Individual talk Radiochemistry in a flash 02.08.2019 Oxford, Great Britain and Northern Ireland Holland Jason;
Departmental seminar Individual talk Advanced synthesis of radiotracers for imaging cancer biomarkers 10.07.2019 Caen, France Holland Jason;
University of Nantes, Special Symposium on Radiopharmaceutical Sciences Individual talk Zirconium radiochemistry: new approaches for labelling bioactive molecules 21.06.2019 Nantes, France Holland Jason;
International Symposium on Radiopharmaceutical Sciences Poster Investigations on the mechanism of simultaneous photochemical conjugation and radiolabelling of proteins with modified arylazides 30.05.2019 Beijing, China Holland Jason;
International Symposium on Radiopharmaceutical Sciences Talk given at a conference Supramolecular Radiochemistry - Cooperative capture synthesis for the development of novel radiotracers 30.05.2019 Beijing, China Holland Jason;
International Symposium on Radiopharmaceutical Sciences Talk given at a conference Preclinical evaluation of a 68Ga-labeled bombesin antagonist comprising the bifunctional chelator NODIA-Me 30.05.2019 Beijing, China Holland Jason;
International Symposium on Radiopharmaceutical Science Poster Broken symmetry copper complexes of photoactive bis(thiosemicarbazone) ligands for chromophore enhancement of photoradiochemical kinetics 30.05.2019 Beijing, China Holland Jason; Esteban Flores Jose;
International Symposium on Radiopharmaceutical Sciences Poster Simultaneous photochemical conjugation and 89Zr-radiolabelling of antibodies for immuno-PET 30.05.2019 Beijing, China Holland Jason;
Synthesis of HBED-CC-ArN3 and immunoPET of c-MET using photoradiolabelled [68Ga]GaHBED-CC-MetMAb Poster Synthesis of a photoactivatable aryl-azide-SAAC ligand and in vivo studies with the photochemically conjugated [99mTc][Tc(CO)3(SAAC-azepin)]-MetMAb 30.05.2019 Beijing, China Holland Jason;
International Symposium on Radiopharmaceutical Sciences Talk given at a conference Synthesis of HBED-CC-ArN3 and immunoPET of c-MET using photoradiolabelled [68Ga]GaHBED-CC-MetMAb 30.05.2019 Beijing, China Holland Jason;
International Symposium on Radiopharmaceutical Science Talk given at a conference Functionalised graphene nanoflakes as potential theranostic agents 30.05.2019 Beijing, China Lamb Jennifer; Holland Jason;
Departmental Seminar Individual talk Radiochemistry in a flash: applications of photochemistry in radiotracers synthesis 08.05.2019 Freiburg, Germany Holland Jason;
Seminar on Radiochemistry Individual talk Radiotracers for PET imaging of cancer signalling pathways 07.09.2018 Lausanne, Switzerland Holland Jason;
Invited departmental seminars Individual talk Zirconium-89 radiochemistry: PET imaging of cancer signalling pathways 30.05.2018 University fo Toronto, Canada Holland Jason;
Canadian Society of Chemistry Talk given at a conference Alternative methods for radiolabelling nanoparticles and biomolecules 28.05.2018 Edmonton, Canada Holland Jason;
Andrew McCawley Memorial Lecture Individual talk Radiochemistry and molecular imaging of cancer biomarkers 31.01.2018 University of York, Great Britain and Northern Ireland Holland Jason;


Self-organised

Title Date Place
Radiochemistry Workshop 15.01.2018 Zurich, Switzerland

Communication with the public

Communication Title Media Place Year
Media relations: print media, online media Simple and Fast Method for Radiolabelling Antibodies against Breast Cancer University of Zurich Press Release International 2019
Talks/events/exhibitions Chemie Forschungs Aktuell 130917 - Radiochemistry and Molecular Imaging of Cancer Biomarkers German-speaking Switzerland 2017
Talks/events/exhibitions PET imaging of oncogenic signalling pathways International 2017

Awards

Title Year
Alavi-Mandell Award from the Society of Nuclear Medicine and Molecular Imaging (SNMMI) 2019

Associated projects

Number Title Start Funding scheme
190093 Radiochemistry in a Flash: Advanced methods for the synthesis of multi-modal imaging agents 01.04.2020 SNSF Professorships
190093 Radiochemistry in a Flash: Advanced methods for the synthesis of multi-modal imaging agents 01.04.2020 SNSF Professorships

Abstract

Nanomedicine is the medical application of nanotechnology to diagnose or treat disease. Increased availability of clinical Positron Emission Tomography/Magnetic Resonance Imaging (PET/MRI) scanners means there is now an urgent need to develop new molecular imaging (MI) agents that can simultaneously take advantage of the functional and anatomic information available from hybrid imaging. Nanoparticles offer a unique opportunity for designing novel multi-modal MI agents. However, at present there are no general methods available for rapid, facile and versatile radiolabelling of nanoparticles using a variety of different nuclides. This SNSF Professorship will address this critical need by i) identifying and characterising new radiolabelling methods, and ii) exploring the potential of multi-modal imaging to measure dynamic biochemical changes in various cancer signaling pathways in response to chemotherapy.
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