Receptor-binding, biodistribution, dosimetry, and micro-SPECT/CT imaging of 111In-[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 111InCl(3). Biologic activity of 111In-[DTPA(1), Lys(3), Tyr(4)]-BN was evaluated in PC-3 prostate tumor-bearing severely compromised immunodeficient (SCID) mice. The purity of synthesized [DTPA(1), Lys(3), Tyr(4)]-BN was greater than 95%. The radiolabeling efficiency of 111In-[DTPA(1), Lys(3), Tyr(4)]-BN was 96.9% +/- 2.46%. The IC(50) and K(i) of [DTPA(1), Lys(3), Tyr(4)]-BN in the human bombesin 2 receptor were 1.05 +/- 0.46 and 0.83 +/- 0.36 nM, respectively. The K(d) of 111In-[DTPA(1), Lys(3), Tyr(4)]-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-[DTPA(1), Lys(3), Tyr(4)]-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-[DTPA(1), Lys(3), Tyr(4)]-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-[DTPA(1), Lys(3), Tyr(4)]-BN is a potential agent for imaging GRPR-positive tumors in humans.

• Authors: Chung-Li Ho, Liang-Cheng Chen, Wan-Chi Lee, Shu-Pei Chiu, Wei-Chuan Hsu, Yu-Hsien Wu, Chung-Hsin Yeh, Michael G Stabin, Meei-Ling Jan, Wuu-Jyh Lin, Te-Wei Lee, Chih-Hsien Chang
• Journal: Cancer biotherapy & radiopharmaceuticals (Cancer Biother Radiopharm) Vol. 24 Issue 4 Pg. 435-43 (Aug 2009) ISSN: 1557-8852 [Electronic] United States
• PMID: 19694578 (Publication Type: Journal Article)

Chemical References

• DTPA(1)-Lys(3),Tyr(4)bombesin
• Indium Radioisotopes
• Radiopharmaceuticals
• Receptors, Bombesin
• Pentetic Acid
• Bombesin

Topics

• Animals
• Binding, Competitive
• Bombesin (analogs & derivatives, chemistry, pharmacokinetics)
• Cell Line, Tumor
• Disease Models, Animal
• Drug Stability
• Female
• Humans
• Indium Radioisotopes (chemistry)
• Isotope Labeling (methods)
• Male
• Mice
• Mice, SCID
• Pentetic Acid (pharmacokinetics)
• Prostatic Neoplasms (diagnostic imaging, metabolism, pathology)
• Radiometry
• Radiopharmaceuticals (chemistry, pharmacokinetics)
• Radiotherapy Dosage
• Receptors, Bombesin (chemistry, metabolism)
• Tissue Distribution
• Tomography, Emission-Computed, Single-Photon (methods)
• Tomography, X-Ray Computed