A comparative in vitro study of well-established PSMA-radioligands and the novel Zr-89-Df-PSMA

Ziel/Aim Many radioligands targeting PSMA have been developed to diagnose or treat the prostate cancer. Their success resides in their high affinity for PSMA as well as the sustained retention in the tumor. The retention is achieved mainly by the internalization of the respective radioligand. In this study, we compared the differences between Ga-68-PSMA 11, Lu-177-PSMA 617, F-18-JK-PSMA 7, Tc-99 m-PSMA I&S and the novel Zr-89-Df-PSMA regarding their affinity, internalization and lipophilicity.

Methodik/Methods The radioligands were characterized in vitro by the calculation of the equilibrium dissociation contestant (K_d) and the internalization in PSMA positive LNCaP cells as well as the octanol-water partition coefficient (log P). The internalization were studied in 10⁶ cells/well at 37 ^oC over a period of time 5 h with samples at 0.5 h, 1 h, 2 h, 3 h and 5 h.

Ergebnisse/Results All compounds showed high affinity for PSMA with K_d values in the same order of magnitude (around 5 nM) with the exception of Tc-99 m-PSMA I&S (15.83 ± 2.0 nM). The cellular uptake and the internalization profiles of the radioligands were comparable with approximately 50 % of the cell-associated activity internalized after 3 h of incubation except forF-18-JK-PSMA 7 that was at all times lower. The log P of Zr-89-Df-PSMA was −3.87 ± 0.02. Ga-68-PSMA 11 was the less lipophilic compound with −4.32 ± 0.14 and the more lipophilic was Tc-99 m-PSMA I&S with −2.82 ± 0.07. The values for Lu-177-PSMA 617 and F-18-JK-PSMA 7 were −4.17 ± 0.13 and −3.77 ± 0.1, respectively.

Schlussfolgerungen/Conclusions The lipophilicity of a PSMA-affine substance drives internalization. When accumulating in the tumor cells, high lipophilicity can balance out a lower affinity.