Development and radiosynthesis of a novel bifunctional tri-γ-glutamic acid polypeptide for gallium-68 labeling

Abstract

Radiosynthesis of a novel bifunctional chelator for gallium-68 (Ga-68) chelation has been fabricated through 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 406.1378 that well corresponded with proposed structure of three repeating unit of glutamic acids. To label Ga-68 with synthesized tri-γ-GAP, the elution of68GaCl3 was chelated to tri-γ-GAP with high temperature condition. It was subsequently purified through Sep-Pak C18 cartridge. Radio thin-layer chromatography demonstrated that the labeling efficiency of68Ga-tri-γ-GAP was 3.5–3.8 mCi with radiochemical purity more than 98%. The pH was 4.5–5.0. Conclusively, synthesized tri-γ-GAP comprising 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 labeling. It is able to link with pharmacological substances without any further modification whereas NOTA needs 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 labeling with versatile application in radiopharmaceutical diagnosis.