Abstract
1597
Objectives Gastrin-releasing peptide receptors (GRPR) are overexpressed on a variety of human tumors like 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 analogue with 111InCl3. Biological activity of 111In-DTPA-BN was evaluated in PC-3 prostate tumor-bearing SCID mice.
Methods A solid phase approach was used to synthesize DTPA-BN. The affinity of DTPA-BN to BN type 2 receptor was determined by a competitive displacement cell-binding assay using 125I-Tyr4-BN. MicroSPECT/CT and biodistribution were performed after iv injection of 111In-DTPA-BN.
Results The purity of synthesized DTPA-BN was greater than 95%. The radiochemical purity of 111In-DTPA-BN was 96.9% ± 2.46%. The IC50 and Ki of DTPA-BN in the human bombesin 2 receptor were 1.05 ± 0.46 nM and 0.83 ± 0.36 nM, respectively. Both biodistribution and micro-SPECT/CT imaging studies with 111In-DTPA-BN demonstrated the highest uptake at 8 hour post-injection. The Pearson correlation analysis showed a positive correlation of tumor uptake between biodistribution and micro-SPECT/CT semi-quantification imaging analysis (r=0.832).
Conclusions Our result revealed111In-DTPA-BN has high affinity with BN type 2 receptor. The results demonstrated a good uptake in the GRPR-over expression PC-3 tumor-bearing SCID mice. 111In-DTPA-BN is a potential agent for imaging GRPR-positive tumors in humans.
- © 2009 by Society of Nuclear Medicine