Preparation of a lyophilized kit based on the DOTA-TATE peptide ligand and the high-specific-activity radiopharmaceutical “[177Lu]Lu-DOTA-TATE, for injection”
摘要
This study is devoted to investigating the synthesis of a lyophilized kit (LK) based on the peptide ligand DOTA-TATE, which is used for the preparation of the radiopharmaceutical “[177Lu]Lu-DOTA-TATE, for injection”. This radiopharmaceutical is applied in specialized nuclear medicine clinical laboratories for the treatment of patients with gastroenteropancreatic (GEP) neuroendocrine tumors (NETs). The radiopharmaceutical was prepared by adding the required activity of the [177Lu]LuCl3 precursor to the lyophilized kit, followed by incubation under controlled conditions. During the preparation of the lyophilized kit [DOTA-TATE], the amount of the peptide ligand DOTA-TATE was fixed at 100 µg per vial. The quantities of the stabilizing agents, ascorbic acid and L-cysteine, were varied in the ranges of 20–150 mg/vial and 0.2–1.2 mg/vial, respectively. The molar ratio of the peptide ligand DOTA-TATE to the [177Lu]LuCl3 precursor used for the synthesis of the radiopharmaceutical “[177Lu]Lu-DOTA-TATE, for injection” was varied from 2:1 to 6:1 in order to determine the optimal labeling conditions. The optimal composition of the lyophilized kit components was established with DOTA-TATE/ascorbic acid/L-cysteine contents of 100 µg/50 mg/1.0 mg per vial. The preparation of the radiopharmaceutical “[177Lu]Lu-DOTA-TATE, for injection” with high specific activity and high radiochemical purity was achieved at a peptide ligand DOTA-TATE to radionuclide 177Lu ratio of 4:1 in the lyophilized kit. The synthesized lyophilized kit [DOTA-TATE] enables the preparation of the radiopharmaceutical “[177Lu]Lu-DOTA-TATE, for injection” with high quality characteristics directly in clinical settings. The radiopharmaceutical is obtained by adding the required activity of the precursor substance “Lutetium chloride [177Lu]LuCl3, no-carrier-added” to the lyophilized kit [DOTA-TATE] at activities up to 10.2 GBq, followed by administration of the freshly prepared radiopharmaceutical to patients.