Development of a Tetrathioether (S4) Bifunctional Chelate System for Rh-105
Annual summary rept. 15 Jun 2011-14 Jun 2013
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Rhodium-105 is an attractive nuclide for radiotherapeutic applications due to its nuclear properties 566 keV beta-.gamma 319 keV 19, 306 keV 5 and the kinetic stability of Rhodium III complexes with soft sulfur donor atoms. Extension of previous research involving tetrathioether chelate systems to include a targeting molecule may have implications for prostate cancer therapy. This work reports on the synthesis and evaluation of a new bombesin peptide targeted Rh III tetrathioether analogue, Rh-S4-8Aoc-BBN7-14NH2, which shows high affinity for the BB2r receptor on PC-3 cancer cells ICsub50 2.2 - 0.3 nM. However, multiple 105Rh labeled species were obtained under the radiolabeling conditions investigated. To better understand the results observed for 105Rh-8Aoc-BBN7-14NH2, the chemistries of previously investigated Rh-S4-Diol and Rh-S4-COOH2 were re-evaluated using more recently available techniques. A quantitative evaluation of the Rh-S4-Diol and Rh-S4-COOH2 systems using NMR, ESI-MS and HPLC reveals formation of multiple species resulting from both exchange of the coordinated chlorides at the metal center and esterification of pendant carboxylate groups. While a predominate trans-chloro RhIII-S4 species may be favored by addition of excess NaCl, both ethanol and acid are required for radiolabeling. Thus, ligand systems utilizing pendant carboxylate groups are not compatible with traditional 105Rh radiolabeling techniques. Future studies involving a 105Rh tetrathioether bombesin analogue without pendant carboxylate groups are recommended.
- Medicine and Medical Research