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Updated: Jun 30, 2026
Avidity-based Extracellular Interaction Screening (AVEXIS) for the Scalable Detection of Low-affinity Extracellular Receptor-Ligand Interactions
Published on: March 5, 2012
Design, synthesis, and biological evaluation of an antagonist-bombesin analogue as targeting vector
Wael R Abd-Elgaliel1, Fabio Gallazzi, Jered C Garrison
1Department of Chemistry, University of Missouri-Columbia, Columbia, Missouri 65211, USA. levers@missouri.edu.
Abstract:
The gastrin releasing peptide receptor (GRP-R) is overexpressed on a number of tumors and cancer cell lines including pancreas, prostate, breast, gastrointestinal, and small cell lung cancer (SCLC). Radiolabeled bombesin (BBN) analogues have exhibited high binding affinity and specificity to the GRP-R. A bombesin analogue with an antagonist targeting vector at the C-terminus, DOTA-aminohexanoyl-[D-Phe(6), Leu-NHCH 2CH 2CH3(13), des Met(14)] BBN[6-14] (1, "Bomproamide"), has been synthesized and displays high binding affinity (IC50 = 1.36 +/- 0.09 nM) against (125)I-Tyr (4)-BBN in in vitro competitive assays using PC-3 cells. Maximum internalization of (111)In-1 reached 14% in PC-3 cells after 45 min of incubation. Rapid (0.25 h PI) and high (12.21 +/- 3.2%ID/g) pancreatic uptake of (111)In-1 was observed in healthy CF-1 mice, and 90% of the activity was blocked by coinjection of 100 mug of BBN. Rapid (0.25 h PI) and high uptake (6.90 +/- 1.06%ID/g) was observed in PC-3 prostate cancer xenografts in SCID mice, as well as visualized clearly in a SPECT/CT study. These results support the use of a bombesin construct with an antagonist C-terminal vector as a candidate of choice for specific in vivo imaging of tumors overexpressing GRP-receptors.
Insights
A novel bombesin analogue, Bomproamide, shows high binding affinity for gastrin releasing peptide receptors (GRP-R). This compound demonstrates potential for in vivo imaging of GRP-R-overexpressing tumors, including prostate cancer.
Area of Science:
- Oncology
- Radiopharmaceutical Chemistry
- Molecular Imaging
Background:
- Gastrin releasing peptide receptor (GRP-R) is overexpressed in various cancers like pancreas, prostate, breast, gastrointestinal, and small cell lung cancer (SCLC).
- Radiolabeled bombesin (BBN) analogues are known for high binding affinity and specificity to GRP-R, making them promising for targeted therapies and imaging.
Purpose of the Study:
- To synthesize and evaluate a novel bombesin analogue, Bomproamide, with an antagonist targeting vector for GRP-R.
- To assess the binding affinity, internalization, and in vivo imaging potential of Bomproamide in GRP-R-expressing cancer models.
Main Methods:
- Synthesis of DOTA-aminohexanoyl-[D-Phe(6), Leu-NHCH 2CH 2CH3(13), des Met(14)] BBN[6-14] (Bomproamide).
- In vitro competitive binding assays using PC-3 cells to determine IC50 against (125)I-Tyr (4)-BBN.
- Internalization studies in PC-3 cells.
- In vivo biodistribution and SPECT/CT imaging studies in healthy mice and SCID mice bearing PC-3 prostate cancer xenografts.
Main Results:
- Bomproamide exhibited high binding affinity (IC50 = 1.36 +/- 0.09 nM) to GRP-R in vitro.
- (111)In-labeled Bomproamide showed maximum internalization of 14% in PC-3 cells within 45 minutes.
- Rapid and high pancreatic uptake (12.21 +/- 3.2%ID/g at 0.25 h PI) in mice, with 90% blocked by excess BBN.
- Significant uptake (6.90 +/- 1.06%ID/g at 0.25 h PI) in PC-3 prostate cancer xenografts, clearly visualized via SPECT/CT.
Conclusions:
- Bomproamide demonstrates excellent binding affinity and specificity for GRP-R.
- The compound shows promising characteristics for in vivo imaging of GRP-R-expressing tumors.
- A bombesin construct with an antagonist C-terminal vector is a viable candidate for targeted tumor imaging.
