Preclinical evaluation of new GnRH ‐I receptor radionuclide therapy with 177Lu‐peptide tracer

The purpose of this study was to develop preclinical evaluation of a novel radiolabeled gonadotropin ‐releasing hormone (GnRH) receptor targeting peptide for prostate cancer therapy. The new antiproliferative agent of GnRH‐I analogue was developed on the basis of the D‐Trp6‐GnRH‐I scaffold, and in vivo pharmacokinetics and receptor binding affinity were enhanced by the substitution of Gly‐NHNH2 for Gly ‐NH2 at position 10 in D ‐Trp6‐GnRH‐I. To evaluate177Lu ‐DOTA‐triptorelin‐hydrazide as radionuclide therapy of tumor, the quality control tests and preclinical stage assessment were carried out. Solid‐phase method was used to synthesize new peptide. Characterization and purity of peptide were done by mass spectroscopy and high‐performance liqui d chromatography (HPLC). In order to be utilized in targeted therapy, the new GnRH‐I agonist was coupled with pSCN‐Bn‐DOTA. The precipitate crude of DOTA‐triptorelin‐hydrazide was then purified via preparative HPLC. At optimal conditions of time, temperature, ligand amount, and lutetium co ntent, DOTA‐triptorelin‐hydrazide was labeled with177Lu (specific activity not less than 925 GBq/mg). Investigation of the in vivo biodistribution and in vitro studies for177Lu ‐DOTA‐TRPHYD was performed in three different ways, and the binding of radiopeptide to GnRH receptors was expressed on the human cell lines using125I ‐labeled D‐TRP6GnRH ‐I as a tracer, respectively. Synthesized novel GnRH‐...
Source: Journal of Labelled Compounds and Radiopharmaceuticals - Category: Biochemistry Authors: Tags: RESEARCH ARTICLE Source Type: research