Receptor-binding,Biodistribution,Dosimetry,and Micro-SPECT/CT Imaging of 111 In-[DTPA 1,Lys 3,Tyr 4 ]-Bombesin Analog in Human Prostate Tumor-Bearing Mice

Abstract

Gastrin-releasing peptide receptors (GRPRs) are overexpressed on a variety of human tumors, such as prostate, breast, and lung cancer. Bombesin (BN) is a 14-amino-acid peptide with high affinity for these GRPRs. We synthesized DTPA-Q-K-Y-G-N-Q-W-A-V-G-H-L-M, a 13-amino-acid peptide chelated with diethylenetriaminepentaacetic acid (DTPA), and radiolabeled this BN analog with ¹¹¹InCl₃. Biologic activity of ¹¹¹In-[DTPA¹, Lys³, Tyr⁴]-BN was evaluated in PC-3 prostate tumor-bearing severely compromised immunodeficient (SCID) mice. The purity of synthesized [DTPA¹, Lys³, Tyr⁴]-BN was greater than 95%. The radiolabeling efficiency of ¹¹¹In-[DTPA¹, Lys³, Tyr⁴]-BN was 96.9% ± 2.46%. The IC₅₀ and K_i of [DTPA¹, Lys³, Tyr⁴]-BN in the human bombesin 2 receptor were 1.05 ± 0.46 and 0.83 ± 0.36 nM, respectively. The K_d of ¹¹¹In-[DTPA¹, Lys³, Tyr⁴]-BN in GRPR-expressing PC-3 tumor cells was 22.9 ± 6.81 nM. Both biodistribution and micro-SPECT/CT (single-photon emission computed tomography/computed tomography) imaging studies with ¹¹¹In-[DTPA¹, Lys³, Tyr⁴]-BN demonstrated the highest uptake at 8 hours postinjection. The Pearson correlation analysis showed a positive correlation of tumor uptake between biodistribution and micro-SPECT/CT semiquantification imaging analysis (r = 0.832). Our results revealed ¹¹¹In-[DTPA¹, Lys³, Tyr⁴]-BN has high affinity with BN type 2 receptor. The results demonstrated a good uptake in the GRPR-overexpression of PC-3 tumor-bearing SCID mice. ¹¹¹In-[DTPA¹, Lys³, Tyr⁴]-BN is a potential agent for imaging GRPR-positive tumors in humans.