PRECLINICAL PET/CT OF PROLONGED TUMOR GROWTH AFTER 177LU-PSMA TREATMENT IN XENOGRAFT MODEL OF HUMAN PROSTATIC CANCER

Abstract

BACKGROUND: New treatment methods of castration-resistant prostate cancer with radionuclide therapy are needed. New methods will optimize personalized strategy for radionuclide therapy of metastatic castrate-resistant prostate cancer using low molecular weight ligands to PSMA labeled with lutetium-177. AIMS: To define the long-term effects and effectiveness of the treatment experimental animals with PET imaging to refine the research strategy. MATERIALS AND METHODS: The study was performed in nu/nu male mice with PSMA-expressing 22Rv1 prostate cancer xenografts. PET/CT study with 18F-PSMA-1007 was used to confirm the tumor regrowth after a single therapeutic dose of [177Lu]Lu-PSMA IT. RESULTS: PET imaging with 18F-PSMA-1007 showed the possibility of prolonged 22Rv1 tumor regrowth after a single injection of 9.2 MBq [177Lu]Lu-PSMA IT, which is equivalent to minimal human therapeutic dose (28.6 MBq/kg). CONCLUSIONS: The study confirmed the short period of the observed therapeutic effect after a single injection of 9.2 MBq [177Lu]Lu-PSMA IT. The tumor regrowth in 2.5 months after the reduction of 22Rv1 xenografts to a non-palpable state was confirmed by PET/CT with 18F-PSMA-1007. These results confirm the need to study the frequency of repeated administrations of radiopharmaceuticals based on ligands to PSMA labeled with lutetium-177 to achieve a stable therapeutic effect in cases where a single dose reduction is necessary. Keywords Radiopharmaceuticals, xenograft, tumor, castration-resistant prostate cancer, 177Lu, 18F