Effect of specific activity on the uptake of [68Ga]-DKFZ-PSMA11 in tumor and other organs

Objectives Radiolabeled small molecule PSMA inhibitors are rapidly entering the clinic for imaging and therapy of prostate cancer. However, there are very few data how the mass of the inhibitor injected affects radiotracer uptake by prostate cancer and normal organs.

Methods Gallium-68 was produced on cyclotron using NCM’s proprietary solid target technology using cyclotron to produce high amount of starting radioactivity (~2 Ci/batch). The PSMA inhibitor [⁶⁸Ga]-DP11 (“HBED-CC-PSMA” or “DKFZ-PSMA11”) was synthesized by addition of 10 µg of DP11 precursor to a 600 µL solution of [⁶⁸Ga]-Ga(OAc)₃ (7-10 mCi) in NaOAc (0.5 M, pH 4.5) buffer and incubating the reaction mixture at 37 °C for 10 min, followed by purification with C18 sep-pak. To vary the specific activity the product was allowed to decay. Groups of athymic nude mice (n=5) bearing PC3-PIP (PSMA +) and PC3 (PSMA-) bilateral tumor xenografts were administered IV with 100 µCi of [⁶⁸Ga]-DP11 in 100 µl with specific activities of 180, 50, and 11 mCi/µmol. Terminal biodistribution studies were performed 60 min later.

Results [⁶⁸Ga]-DP11 was synthesized in >90% yields (d.c.) with >95% radiochemical purity. Biodistribution studies revealed that the PC3-PIP tumor uptake of mice injected with 100 µCi of [⁶⁸Ga]-DP at a specific activity of 180, 50, 11 mCi/µmol were 10.41 + 1.16, 8.08 + 0.93, and 9.61 + 2.87 %ID/g, respectively. The corresponding kidney uptake values were 90.52 + 19.98, 48.08 + 10.17, and 16.39 + 5.40 %ID/g, respectively. Uptake in PSMA negative PC3 tumors was less than 1 %ID/g for all specific activities.

Conclusions In the studied model, a more than 16-fold decrease of specific activity had no significant effect on tumor uptake of [⁶⁸Ga]-DP11. This suggests that [⁶⁸Ga]-DP11 produced at a central radiopharmacy can be shipped over several half-lifes. The drastic decrease of renal uptake with decreasing specific activity is probably due to saturation of binding sites in the well perfused kidneys whereas tumor uptake appears limited by delivery of [⁶⁸Ga]-DP11 (Figure). Administering a larger mass may therefore decrease renal toxicity of PSMA targeted radionuclide therapy. Supplementary Figures