Tools for the preparation of peptide-based radioligands

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Tools for the preparation of peptide-based radioligands Over the past few years, the development of radiopeptides for diagnostic and therapeutic applications in diverse cancers has seen a significant growth. Peptide-based ligands provide many attractive features, including relative ease of preparation by solid phase techniques and accessible chemical diversity utilizing natural and unnatural amino acids. During the last funding period, I implemented new and robust fast-automated purification processes using cassette-based systems for a routine production of radiometals such as 99mTc, 64Cu, 89Zr and 68Ga by cyclotron. As well, convenient approaches to label peptides and antibodies with radiometals via functionalization with both established and novel bifunctional chelators (BFC) were recently developed in my laboratory for 64Cu, 89Zr 68Ga. In continuity with my earlier work, the present proposal advances the development of emerging and highly promising radiometals, such as 45Ti (t½=3.08h) for PET imaging, and 119Sb (t½=38.2h), an Auger-electron emitter that could offer a high therapeutic index along with a second generation of BFCs. I also propose an improved polymer-supported 18F-radiolabelling procedure for the preparation of a variety of 18F-prosthetic groups and 18F-radiopeptides. My long-term objective is to develop an arsenal of innovative tools-radiometals, BFC, polymer-assisted 18F-labelling-that will improve the labelling, molar activity and/or stability of peptide-based radioligands. In addition to developing an arsenal of powerful alternative synthetic tools and procedures dedicated to the preparation and radiolabelling of peptide conjugates, my program will provide a base for the design of new radiopharmaceuticals that will enlarge the number of medical conditions that can benefit from diagnostic PET imaging and targeted radiotherapy. The research proposed herein will also permit the training of HQPs that will possess a unique combination of skills from synthetic chemistry, radiolabelling, biomedical imaging and radiotherapy in an important field of research. This fundamental science program is a unique opportunity for me to develop molecular tools designed to fine-tune the various biological properties of relevant radiolabelled-peptides used for theranostic applications.