Preparation of [177Lu]PSMA-617 Using Carrier Added (CA) 177Lu for Radionuclide Therapy of Prostate Cancer

Objective: Lutetium-177 labelled PSMA-617 is an emerging radiopharmaceutical for targeted radionuclide therapy of prostate cancer (PCa) and hence there is an interest in the formulation and clinical application of this novel tracer. This paper summarises the studies undertaken to prepare clinical doses of [177Lu]PSMA-617 for therapy of prostate cancer patients. Experimental: [177Lu]PSMA-617 was prepared by reacting 177LuCl3 (5.4 GBq to 15.8 GBq, specific activity 650 MBq/μg to 860 MBq/μg) with 100 μg to 300 μg of PSMA-617 at pH 4.5-5. Radiochemical (RC) yields were estimated by thin layer and paper chromatography. When RC yields were lower than 95% the product was purified using a C18 cartridge which removed unreacted 177LuCl3. Two patients having histopathologically proven PCa and having significant levels of metastasis were given freshly prepared [177Lu]PSMA-617. Results: [177Lu]PSMA-617 could be prepared in high yields using CA low specific activity 177Lu and using modest amounts of ligand. Purification using a C18 cartridge provided the product with high RC purity. The product formed was stable for several days when stored at 4°C. SPECT images acquired post therapy showed that the [177Lu]PSMA-617 accumulated in most lesions identified by [68Ga]PSMA-11 PET-CT imaging. No redistribution of activity accumulated in lesions was seen in images acquired up to 7th day, post therapy. Therapy was well tolerated by the patients with no adverse reaction reported. Conclusion: The studies carried out suggest that therapeutic doses of [177Lu]PSMA-11 could be prepared by using low specific activity, carrier added 177Lu. Clinical studies demonstrated the uptake and retention of the tracer in prostate cancer lesions.