Development of a Ga-68 labeled triptorelin analog for GnRH receptor imaging

Abstract

Abstract Optimized total synthesis, radiolabeling and quality control of [68Ga]-DOTA-Hyd-TRP as an efficient and possible PET radiotracer for GnRH receptor imaging in various tumors is of great interest. DOTA-Hyd-TRP was synthesized using solid phase peptide synthesis followed by conjugation to DOTA using pSCN-Bn-DOTA. [68Ga]-DOTA-Hyd-TRP was prepared using generator-based [68Ga]GaCl3 and DOTA-Hyd-TRP under optimized conditions for time, temperature, ligand amount, gallium content and column cartridge purification followed by proper formulation. The biodistribution of the tracer in rats was studied using tissue counting up to 120 min. [68Ga]-DOTA-Hyd-TRP was prepared at optimized conditions in 5–7 min at 95 ℃ followed by separation using C18 cartridge (radiochemical purity ≈ 99 ± 0.88% ITLC, > 99% HPLC, specific activity: 300 ± 15 MBq/nM). The biodistribution of the tracer demonstrated high kidney uptake of the tracer in 10–20 min as well as significant testicular uptake consistent with reported GnRH receptor mappings. Block test studies by triptorelin pretreatment of the animals prior to tracer administration demonstrated significant specific uptake in receptor rich organs including testes and stomach.