Development and Radiosynthesis of a Novel Bifunctional Tri-γ-Glutamic Acid Polypeptide for Gallium-68 Labeling:(TJPS-2020-0281.R1)

Abstract

Radiosynthesis of a novel bifunctional chelator for gallium-68 (Ga-68) chelation has been fabricated via peptide synthesis. Using of solid phase peptide synthesizer, linear structure of three repeating unit of glutamic acid was primarily generated. Protecting group of tert-Butyl in intermediate was then cleaved and eventually yield as tri-γ-glutamic acid polypeptide (tri-γ-GAP). Mass spectrometry revealed m/z was 406.2148 that well corresponded with proposed structure of three repeating unit of glutamic acids. In order to label Ga-68 with synthesized tri-γ-GAP, the elution of ⁶⁸GaCl₃ was chelated to tri-γ-GAP with high temperature condition. It was subsequently purified via Sep-pak C18 cartridge. Radio thin layer chromatography demonstrated the labelling efficiency of ⁶⁸Ga-tri-γ-GAP was 3.5-3.8 mCi with radiochemical purity more than 98%. The pH was 4.5 to 5.0. Conclusively, synthesized tri-γ-GAP comprising of three N-dentate and four OH-dentate. One more free OH-dentate of tri-γ-GAP provided more applicability over universal chelator of N,N’,N’’-1,4,7,-triazacyclononane-1,4,7-triyl) triacetic acid (NOTA) on Ga-68 labelling. It is able to link with pharmacological substances without any further modification whereas NOTA need to be synthesized a specific linker for an attaching with bioactive pharmacological molecule. Novel small peptide chelator of tri-γ-GAP is a promising molecule for Ga-68 labelling with versatile application in radiopharmaceutical diagnosis.

:TJPS-2020-0281.R1