Development of a Tetrathioether (S4) Bifunctional Chelate System for Rh-105
Abstract
The purpose of this project is to develop and evaluate a potential new molecule for site directed prostate cancer therapy. The moderate - emissions (0.566 MeV [70%], 0.248 MeV [19%], t = 35.4 h) of rhodium-105 are well suited for therapy of solid tumors. In addition to its favorable nuclear properties, the kinetic inertness of low-spin d6 Rh(III) complexes make them good candidates for radiopharmaceutical use. The bifunctional chelate method will be utilized to couple rhodium-105 with a bombesin (BBN) targeting vector. Bombesin targets gastrin releasing peptide (GRP) receptors, which have been shown to be over-expressed on the surface of prostate cancer cells. Here we report the successful synthesis and characterization of a bombesin agonist coupled tetrathioether (S4) bifunctional chelate system (S4-BBN) and the resulting [Rh(III)-S4-BBN]+ complex. Characterization of this previously unknown complex contributes to existing knowledge in the field of radiopharmaceutical chemistry and drug discovery. Studies now underway include in vitro determination of IC50 values employing the PC-3 human prostate cancer cell line and biological evaluation of the [Rh(III)-S4-BBN]+ complex in animal xenograft models. If successful, this project will improve frontline treatment of patients with metastatic prostate cancer.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2012
- Accession Number
- ADA563218
Entities
People
- Don Wycoff
- Fabio Galazzi
- Silvia Jurisson
- Timothy Hoffman
- Valerie Carroll
Organizations
- University of Missouri