Reduced Renal Uptake of ⁶⁸Ga-PSMA-617 by Penta-L-Glutamic Acid Co-Injection

Objectives: Radiolabeled asymmetric urea compounds (Glu-urea-based molecule) have been found useful for imaging and treatment of prostate cancer. The reduction of renal accumulation of the radiolabeled urea compounds would increase diagnostic accuracy and therapeutic effectiveness. In this study, we evaluated the effect of penta-L-glutamic acid (Glu₅) co-injection on the renal accumulation of ⁶⁷Ga-PSMA-617 in mice.

Methods: ⁶⁷Ga-PSMA-617 was injected into normal or LNCap tumor-bearing nude mice with or without Glu₅ (2.5 mg/mouse) or L-Lysine (35 mg/mouse). At 1 h postinjection, tissue distribution of ⁶⁷Ga-PSMA-617 in the mice was compared.

Results: There observed no significant differences in the renal radioactivity levels between ⁶⁷Ga-PSMA-617 with and without L-Lysine. On the other hand, the co-injection of Glu₅ with ⁶⁷Ga-PSMA-617 significantly reduced renal radioactivity levels when compared with ⁶⁷Ga-PSMA-617 without Glu₅. In addition, the tumor radioactivity levels remained unchanged following the co-injection of ⁶⁷Ga-PSMA-617 with Glu₅. No significant differences were observed in the radioactivity levels in other tissue. Conclusions: The co-injection of Glu₅ would constitute a useful way to reduce renal uptake of ⁶⁷Ga-PSMA-617 without impairing the radioactivity levels in the tumor. These results also suggested that the renal reabsorption of ⁶⁷Ga-PSMA-617 at the proximal tubules would be in part responsible for the renal uptake of the compound.