Aim:

To develop a safe and inexpensive method for labeling PSMA inhibitors such as PSMA-I&T and PSMA-617 with Lu-177 for radioligand therapy of metastatic castration-resistant prostate cancer.

Methods:

Lu-177-(III)-chloride solution (300 µL, 5-30 GBq, 0.04 M HCl, ITG) in 2 mL original delivery vial (reaction vessel) was used. PSMA ligand (15-20 µg/GBq Lu-177) and gentisic acid (6-8 mg) were dissolved in sodium acetate buffer (700 µL, 0.4 M, pH = 5.5) and transferred into the radionuclide solution. The reaction mixture was incubated for 30 min at 85 °C. Radiolabeling was carried out in a plexiglass box (beta shielded) in a dedicated beta laboratory under GMP conditions. After cooling, labeling efficiency and radiochemical purity were determined using radio-TLC and -HPLC (RP-18, acetonitrile-water gradient). The solution was then diluted with saline and available for clinical use.

Results:

More than 350 syntheses were performed. The failure rate was < 0.1 %. Regarding the labeling yield, No differences were found between the labeling yields of PSMA-617 and PSMA I&T. The radiochemical purity was more than 99 %. Stability studies showed that after 24 hours the radiochemical purity was still over 95%. However, the quality of the delivered Lu 177-(III)-chloride solution plays a decisive role.

Conclusion:

An efficient method for radiolabeling of PSMA compounds for clinical use was established under GMP conditions. This method can be employed to prepare the other DOTA derivatives (e.g., DOTATOC, DOTATATE) as well.