Evaluation of 111In-Labeled GnRH-I Tracer for SPECT Tumor Imaging

Abstract

Total synthesis, quality control, and preclinical evaluation of [111In]-DOTA-Triptorelin ([111In]-DOTA-TRP) for diagnostic SPECT imaging have been made. For 111In labeling, the peptide synthesis was followed by conjugation with DOTA using pSCN-Bn-DOTA. The synthesized conjugate prepared at optimized conditions was purified with a reversed-phase semipreparative column using gradient of water: acetonitrile mixture. The molecular mass was confirmed by mass spectroscopy. The conjugated Triptorelin was labeled with 500–550 MBq of 111In chloride (in 0.2 M HCl). The radiochemical purity of the product prepared under optimized conditions was about 98% (RTLC) and >95% (HPLC). The serum stability of the tracer was determined up to 24 h. The 111In-peptide chelate exhibits high stability. The binding affinity of Triptorelin peptide was determined in a binding assay for both human and rat GnRH receptors. For in vivo studies, 111In-peptide was injected intravenously via the tail vein to rats. In vitro radioligand binding assays were performed with GnRHR-expressing human cell lines using [125I]Triptorelin as the standard radioligand. The receptor affinity of the new radioligand was IC50 = 0.35 ± 0.08 nM vs. 0.13±0.01 nM for Triptorelin, and the internalization efficiency was 3.4 ± 0.7% at 1 h and 11.8 ± 1.9% at 4 h.