Preclinical positron emission computed tomography of prolonged tumor growth after lutetium-177 prostate-specific membrane antigen treatment in xenograft model of human prostate cancer

Abstract

BACKGROUND: New treatment methods of castration-resistant prostate cancer with radionuclide therapy are needed. They will optimize personalized strategy for radionuclide therapy of metastatic castrate-resistant prostate cancer using low molecular weight ligands to prostate-specific membrane antigen (PSMA) labeled with lutetium-177. AIM: To define the long-term effects and effectiveness of the treatment experimental animals with PET imaging to refine the research strategy. METHODS: The study was performed in nu/nu male mice with PSMA-expressing 22Rv1 prostate cancer xenografts. Positron emission computed tomography with 18F-PSMA-1007 was used to confirm the tumor regrowth after a single therapeutic dose of [177Lu]Lu-PSMA-IT. RESULTS: Positron emission tomography imaging with 18F-PSMA-1007 showed the possibility of prolonged 22Rv1 tumor regrowth after a single injection of 9.2 MBq of [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 of [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 positron emission computed tomography 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.