Development of a super(68)Ga-peptide tracer for PET GnRH1-imaging

Total synthesis, quality control and preclinical evaluation of [ super(68)Ga]-DOTA-triptorelin ([ super(68)Ga]-DOTA-TRP) is reported as a possible PET radiotracer for GnRH receptor imaging. DOTA-TRP was totally synthesized in two steps and after characterization went through radiolabelling optimization studies followed by tracer stability. The biodistribution of the tracer in normal male rats and 4T1 tumour-bearing mice was performed in 120 min after i.v. injection. The peptide and the conjugates were synthesized with >95 % chemical purity. [ super(68)Ga]-DOTA-TRP complex was prepared in high radiochemical purity (>99 %, ITLC, HPLC) and specific activity of 1400-2100 MBq/nM at 95 degree C using 40-60 mu g of the peptide in 5-7 min followed by solid phase purification. The IC sub(50) [nM] DOTA-TRP was comparable to the intact peptide, 0.11 plus or minus 0.01 and 0.22 plus or minus 0.05, respectively. The biodistribution of the tracer demonstrated kidney, stomach, and testes significant uptake, all in accordance with GnRH receptor ligands. Significant tumour uptake was observed in 4T1 tumour-bearing female mice 30-120 min post-injection with tumour:blood and tumour:muscle ratios of 28 and >50 in 60 min, respectively. Kidney is rapidly washed from the tracer. [ super(68)Ga]-DOTA-TRP can be proposed as a possible tracer for GnRH-R imaging studies.