Optimization of the radiosynthesis of the PSMA-targeting drugs [Lu]Lu-P17-087 and [Lu]Lu-P17-088 on the MiniLu™ automated module.
1/5 보강
[BACKGROUND] There is a renewed interest in radioligand therapy for cancer treatment since the approval of Lu-177 vipivotide tetraxetan (PSMA-617) by regulators in Europe and the United States for met
APA
Alexoff D, Ploessl K, et al. (2025). Optimization of the radiosynthesis of the PSMA-targeting drugs [Lu]Lu-P17-087 and [Lu]Lu-P17-088 on the MiniLu™ automated module.. EJNMMI radiopharmacy and chemistry, 10(1), 75. https://doi.org/10.1186/s41181-025-00400-4
MLA
Alexoff D, et al.. "Optimization of the radiosynthesis of the PSMA-targeting drugs [Lu]Lu-P17-087 and [Lu]Lu-P17-088 on the MiniLu™ automated module.." EJNMMI radiopharmacy and chemistry, vol. 10, no. 1, 2025, pp. 75.
PMID
41249585
Abstract
[BACKGROUND] There is a renewed interest in radioligand therapy for cancer treatment since the approval of Lu-177 vipivotide tetraxetan (PSMA-617) by regulators in Europe and the United States for metastatic castrate resistant prostate cancer (mCRPC) patients. Recent expansion of indications for vipivotide tetraxetan in mCRPC by the FDA promises to increase demand for this class of radioligand therapy. The development of new targeted radioligands for mCRPC that improve binding specificity and increase radiation dose delivered to tumors is an active research space. [Lu]Lu-P17-087 and [Lu]Lu-P17-088 are new prostate specific membrane antigen (PSMA) targeted drugs under clinical investigation in China. Heretofore the preparation of these investigational drugs has been carried out manually. This report introduces a new cassette-based, radiosynthesis platform named MiniLu™ and describes the optimization and automation of the preparation of [Lu]Lu-P17-087 and [Lu]Lu-P17-088 for clinical use.
[RESULTS] Radiolabeling of [Lu]Lu-P17-087 was optimized for pH, time, temperature and ligand concentration using 0.2 - 13 MBq of Lu-177 (> 740 GBq/mg) and MiniLu™. > 99% labeling yield measured by thin layer chromatography (TLC) was achieved with a pH = 5, 50-110 °C, 10 min, 3:1 mol ratio ligand: Lu-177; ligand mass > 3 nmole in 0.5 mL reaction solution. Quantitative labeling was confirmed using these conditions (80 °C) in simulations of clinical production doses of Lu-177 (7.4 GBq; > 3000 GBq/mg) by adding cold [Lu]LuCl (14 nmoles). [Lu]Lu-P17-088 labeling yield was > 99% under the identical simulation conditions. A final product yield (activity in dose vial / starting Lu-177 activity) of ~ 95% was achieved after formulation with L-ascorbate and gentisic acid (15 mL) and sterile filtration using MiniLu™ and the simulated high activity conditions for both compounds. Final optimized concentrations for automated dose preparation were 62 µM (0.6 mL) and 70 µM (0.6 mL) for [Lu]Lu-P17-087 and [Lu]Lu-P17-088, respectively. Over 100 independent automated MiniLu™ runs were completed successfully.
[CONCLUSIONS] [Lu]Lu-P17-087 and [Lu]Lu-P17-088 doses can be produced in high yield (95%) and purity (99%) using MiniLu™. Optimized, automated methods using MiniLu™ will facilitate further clinical investigations using [Lu]Lu-P17-087 and [Lu]Lu-P17-088 by standardizing preparation and reducing radiation exposure to radiochemists.
[RESULTS] Radiolabeling of [Lu]Lu-P17-087 was optimized for pH, time, temperature and ligand concentration using 0.2 - 13 MBq of Lu-177 (> 740 GBq/mg) and MiniLu™. > 99% labeling yield measured by thin layer chromatography (TLC) was achieved with a pH = 5, 50-110 °C, 10 min, 3:1 mol ratio ligand: Lu-177; ligand mass > 3 nmole in 0.5 mL reaction solution. Quantitative labeling was confirmed using these conditions (80 °C) in simulations of clinical production doses of Lu-177 (7.4 GBq; > 3000 GBq/mg) by adding cold [Lu]LuCl (14 nmoles). [Lu]Lu-P17-088 labeling yield was > 99% under the identical simulation conditions. A final product yield (activity in dose vial / starting Lu-177 activity) of ~ 95% was achieved after formulation with L-ascorbate and gentisic acid (15 mL) and sterile filtration using MiniLu™ and the simulated high activity conditions for both compounds. Final optimized concentrations for automated dose preparation were 62 µM (0.6 mL) and 70 µM (0.6 mL) for [Lu]Lu-P17-087 and [Lu]Lu-P17-088, respectively. Over 100 independent automated MiniLu™ runs were completed successfully.
[CONCLUSIONS] [Lu]Lu-P17-087 and [Lu]Lu-P17-088 doses can be produced in high yield (95%) and purity (99%) using MiniLu™. Optimized, automated methods using MiniLu™ will facilitate further clinical investigations using [Lu]Lu-P17-087 and [Lu]Lu-P17-088 by standardizing preparation and reducing radiation exposure to radiochemists.