New 68Ga Glu-Urea-Lys(Ahx)-HBED-CC-bisphosponate as a dual-targeted imaging agent for PSMA and bone metastasis.

1395 Objectives Positron emission tomography (PET) imaging using 68Ga labeled Glu-Urea-Lys(Ahx)-HBED-CC-bisphosponate to target both PSMA and bone metastasis may be a valuable tool for diagnosis and monitoring therapeutic treatment of prostate cancer. Methods : 68Ga labeled N,N′-bis[2-hydroxy-5-(carboxyethyl)benzyl] ethylenediamine-N,N′-diacetic acid (HBED-CC) containing one bisphosphonate group and one Glu-Urea-Lys(Ahx) group, 1, was prepared and tested with hydroxyapatite binding assay, PSMA binding assay, biodistribution in mice, and animal PET imaging in LNCaP tumor-bearing mice (a tumor known to over express PSMA). Results The new ligand 1 reacted rapidly in a sodium acetate buffer with [68Ga]GaCl3 eluted from a commercial 68Ge/68Ga generator (pH 4, >98% labeling at room temperature in 10 min) to form [68Ga]1. Because labeling was nearly quantitative, the labeled product was used without further purification. This bisphosphonate, [68Ga]1, showed a strong binding to hydroxyapatite and it also retained high affinity to PSMA comparable to a known PSMA imaging agent, [68Ga]Glu-Urea-Lys(Ahx)-HBED-CC. The biodistribution of [68Ga]1 in normal mice showed excellent bone uptake and retention. In addition, a significant uptake in kidneys was observed, suggesting that [68Ga]1 also targeted PSMA sites in the kidneys. MicroPET imaging studies in mice with xenographed LNCaP tumor overexpressing PSMA showed high uptake in the tumor as well as in the bone. Conclusions The results suggest that [68Ga]1 may be suitable as a dual targeting imaging agent for PSMA and bone metastasis. Also, This dual-targeted imaging agents, [68Ga]1, may show improved sensitivity and specificity for detecting bone metastasis.