Project title: Efficient automated synthesis of silicon-[18F]fluoride acceptor (SiFA)-based neuroendocrine tumour imaging agents via “non-anhydrous, minimally basic” (NAMB) radio-fluorination chemistry.

Description

Dr. Inkster will develop state-of-the-art ¹⁸F radiolabeling methods designed to a) simplify the clinical production of peptide-based PET tracers targeting gastroenteropancreatic neuroendocrine tumors (GEP-NETs) and b) facilitate the invention of novel ¹⁸F-labelled peptide hormone analogues useful for the diagnosis and localization of insulinomas.

What critical NET problem will you try to solve through your research?

The development of ¹⁸F-GEP-NET tracers has been impeded by synthetic challenges associated with the laborious radio-bioconjugation methods designed to indirectly radiolabel ligands of NET-associated peptide receptors under the automated conditions required for clinical use.

Why is this important?

Flourine-18 exhibits second-to-none PET imaging characteristics and is increasingly available due to worldwide demand for [¹⁸F]FDG. Thus, ¹⁸F-GEP-NET imaging agents that exhibit all the advantages of their radio-metalated (e.g. ¹¹¹In, ⁶⁸Ga) counterparts- namely, the straightforward, kit-like preparation of high molar activity radiopharmaceutical via automated synthesizers- would be highly desirable.

What will you do as part of this research project?

By merging two non-canonical ¹⁸F-labeling strategies- Silicon-[¹⁸F]fluoride Acceptor (SiFA) ¹⁹F-for-¹⁸F isotopic exchange and “non-anhydrous, minimally basic” (NAMB) ¹⁸F-fluorination chemistry, the Inkster lab plans to design and validate a single-step, automated radiosynthesis of a SiFA-modified Tyr³-octreotate derivative. These learnings with then be leveraged towards the design, synthesis and small animal PET assessment of novel SiFAylated peptides targeting the glucagon-like peptide 1 (GLP-1) receptor for insulinoma imaging.

How might your research improve the diagnosis and/or treatment of NETs?

This research seeks to generally improve and expand the clinical utility of high resolution ¹⁸F-PET imaging for NET diagnosis, staging and evaluation of therapeutic efforts. Regarding the treatment of insulinoma-induced hypoglycemia specifically, successful pre-operative imaging permits determination of tumor location on the pancreas and can guide the choice of full pancreatic resection vs partial resection vs tumor enucleation. The use of radio-metalated peptides for this application usually results in extensive renal uptake, which can complicate the delineation of nearby pancreatic lesions. The ¹⁸F-labelled GLP-1 receptor agonists developed in the Inkster lab are expected to exhibit reduced kidney retention, resulting in improved PET images.

What is your next step?

Establishment of a simple, reproducible and automated radiosynthetic protocol will permit preclinical assay of an expanded library of peptide sequences and pendant modifications. Highly promising GEP-NET tracers will be singled out for further translational development in collaboration with clinical researchers.

« Back to all funded research projects