Improving the radiosynthesis of peptides and antibodies for nuclear imaging of cell surface receptors development and

Lead Research Organisation: MRC London Institute of Medical Sciences


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Technical Summary

The discovery to be developed. We wish to develop a generic click chemistry approach for radiolabelling peptides and antibodies. Within the last two years a new 18F labelling method involving chemoselective Cu(I)-catalyzed Huisgen cycloaddition, also known as the "click reaction", has been discovered. This reaction permits facile, high efficiency chemoselective radiolabelling of peptides and antibodies with the optimal positron emitting radioisotope fluorine-18. Generic radiolabelling of peptides will permit several cell surface receptors to be imaged in living subjects by positron emission tomography (PET). Furthermore, generic radiolabelling of antibodies with this or similar methods that permit use of longer lived radioisotopes such as 64Cu will permit early high resolution imaging of initial peptide/antibody delivery in humans when done in a pre-phase I setting. This strategy coupled with small dose escalation and complete cytokine profiling may offer a better approach to developing peptide/antibody therapeutics than the current reliance on rodents and monkeys models. The rationale for development. We will initially test the utility of the generic click radiolabelling reaction by labelling a small peptide, octreotide, already in the clinic as a c-imaging radiopharmaceutical, and assess its value in neuroendocrine tumours (NETs) by PET. The capabilities of your laboratory to undertake the proposed research, including project management expertise. The radiochemistry development will be undertaken by Hammersmith Imanet. Dr Glaser is a co-inventor of the clickradiochemistry approach. The Molecular Therapy group (Prof. Aboagye) has extensive expertise in the testing of new radiotracers in pre-clinical models and cancer patients; Dr Al-Nahhas has experience in the use of octreotide radiotracers in patients. The immunology group supervised by Prof. George has extensive expertise in cytokine profiling, phage libraries and modification of peptides/antibodies for labelling. Any requirements for external collaborations or outsourcing of activities. We will outsource the radiochemistry development component of this project to Hammersmith Imanet. Desired outcomes including potential for commercial exploitation. Development of a generic approach for rapidly translating peptide/antibody research into patients. A new octreotide radiopharmaceutical for imaging NETs. The fluorinated octreotide will be a new chemical entity and, hence, a potential for commercial exploitation for imaging NETs. Existing IPR landscape. The click-radiochemistry method has been patented by GE-Healthcare. Any other information you feel is important to the application. Proof-of-principle dynamic PET/CT imaging will be performed in patients with NETs to assess the diagnostic value of the new radiotracer.
Description MRC Developmental Pathway Funding Scheme (DPFS)
Amount £380,383 (GBP)
Funding ID G0801762 
Organisation Medical Research Council (MRC) 
Sector Public
Country United Kingdom
Start 03/2009 
End 02/2011
Title novel 18F-fluoroethyltriazole-Tyr3-octreotate analogs for PET 
Description A new 18F labelled compound to allow the improved PET scanning of gastroenteropancreatic neuroendocrine tumors 
Type Of Material Technology assay or reagent 
Year Produced 2012 
Provided To Others? Yes  
Impact This new material has shown promise pre-clinically as a potential new gold standard for the assessment of gastroenteropancreatic neuroendocrine tumors. This has lead to a DCS application to allow the first-in-man studies of this compound as a first step to obtaining evidence to challenge the exisiting gold standard diagnosis and assessment tool for these tumours. 
Description GE Healthcare FETO 
Organisation GE Healthcare Limited
Department MDx Discovery
Country United Kingdom 
Sector Private 
PI Contribution Personnel from the Group worked on the Biology side of the project and undertook all biology work associated with this project. We obtained DCS funding for a clincial study of the compound and staff will be undertaking this, along with the chemistry development to allow delivery for human use.
Collaborator Contribution The DPFS was a collaborative project with GE providing consumables, techniques, training, knowledge to suppliment the science and personnel which we brought to the project. GE have provided knowledge for FASTlab development at Imanova plus assistance with provision of FASTlab cassettes.
Impact Two papers published (PMID 21458258 and 21852355). Also a jointly held patent on the candidate tracers developed as part of this project.
Start Year 2013
Description GE Healthcare MDx 
Organisation GE Healthcare Limited
Department Medical Diagnostics (MDX)
Country United States 
Sector Private 
PI Contribution A joint steering committee to look at work (pre-clinical and clinical) where we wish to do work which involve GE tracers/compounds. Our work has fed back to GE regarding their tracers and also assisted in development into First in Man studies of jointly developed tracers.
Collaborator Contribution They have provided knowledge, FASTlab cassettes, compounds and delivery of tracers at an academic study charge (or free of charge) depending on level of collaboration.
Impact First in Man studies of new compounds.
Start Year 2013
Description Imanova 
Organisation Imanova
Country United Kingdom 
Sector Private 
PI Contribution We have provided personnel to allow the transition of tracers we have developed into First in Man studies.
Collaborator Contribution We have been able to use the very high level radiochemistry development labs.
Impact None as yet
Start Year 2013
Description Novel radiotracer(s) for Positron Emission Tomography (PET) imaging are described. Novel radiotracer(s) for Positron Emission Tomography (PET) imaging of neuorendocrine tumors are described. Specifically the present invention describes novel [18F]Fluoroethyltriazol-[Tyr3]Octreotate analogs; in particular those that target somatostatin receptors found on the cell surface of gastroenteropancreatic neuorendocrine tumors. The present invention also describes intermediate(s), precursor(s), pharmaceutical composition(s), methods of making, and methods of use of the novel radiotracer(s). 
IP Reference WO2012118909 
Protection Patent granted
Year Protection Granted 2012
Licensed No
Impact This compound will be undergoing First In Man trials under an MRC DCS grant.
Title novel [18F]Fluoroethyltriazol-[Tyr3]Octreotate analogues 
Description The DPFS grant allowed development of the new imaging compound and pre-clinical assessment to be completed. We have now applied for a DCS grant to allow clinical testing. 
Type Diagnostic Tool - Imaging
Current Stage Of Development Refinement. Non-clinical
Year Development Stage Completed 2010
Development Status Under active development/distribution
Impact Analogues developed resulted in a patent filing. First in Man study due to start end of 2012.