Nucleophilic 18F-Labelling of Galectin-3 Inhibitors for PET Analysis

Abstract: Galectins are a family of proteins naturally occurring in humans involved in a broad variety of bodily functions, including regulation of immune response and inflammation. The most studied protein of the family, galectin-3, has repeatedly been proven to be involved in tumour progression, affecting both tumour survival and metastasis. Both in vitro and in vivo analyses have yielded information that emphasizes the importance of galectin-3 inhibition for development of cancer therapeutics. An established technique to study a substance’s biodistribution through the body is by positron emission tomography. By injecting a radiolabelled pharmaceutical, it is possible to study its biological properties, such as uptake, elimination, etc. Three precursors to radiolabelled galectin-3 inhibitors were synthesised successfully. Labelling reactions were performed by 18F-fluorination, followed by deprotection. Only one precursor, a boronic pinacol ester, was successfully labelled to form a radioactive galection-3 inhibitor, in a Cu-mediated reaction. The crude product was purified by preparative high performance liquid chromatography and the isolated product was transferred to a suitable solvent via a solid phase extraction to yield a radiochemical pure product that can be further used in man for positron emission tomography studies.