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

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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.