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 Ki of [DTPA1, Lys3, Tyr4]-BN in the human bombesin 2 receptor were 1.05 ± 0.46 and 0.83 ± 0.36 nM, respectively. The Kd 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.