Preparation of Rh[16aneS4-diol]211At and Ir[16aneS4-diol]211At Complexes as Potential Precursors for Astatine Radiopharmaceuticals. Part I: Synthesis
- 14 March 2008
- journal article
- research article
- Published by American Chemical Society (ACS) in Bioconjugate Chemistry
- Vol. 19 (4), 958-965
- https://doi.org/10.1021/bc700413r
Abstract
The goal of this study was to evaluate a new approach that can be applied for labeling biomolecules with 211At. Many astatine compounds that have been synthesized are unstable in vivo, providing motivation for seeking different 211At labeling strategies. The approach evaluated in this study was to attach astatide anions to soft metal cations, which are also complexed by a bifunctional ligand. Ultimately, this complex could in principle be subsequently conjugated to a biomolecule with the proper selection of ligand functionality. We report here the attachment of 211At− and *I− (*I = 131I or 125I) anions to the soft metal cations Rh(III) and Ir(III), which are complexed by the 1,5,9,13-tetrathiacyclohexadecane-3,11-diol (16aneS4-diol) ligand. Radioactive *I− anions were used for preliminary studies directed at the optimization of reaction conditions and to provide a baseline for comparison of results with 211At. Four complexes Rh[16aneS4-diol]*I/211At and Ir[16aneS4-diol]*I/211At were synthesized in high yield in a one-step procedure, and the products were characterized mainly by paper electrophoresis and reversed-phase HPLC. The influences of time and temperature of heating and concentrations of metal cations and sulfur ligand 16aneS4-diol, as well as pH on the reaction yields were determined. Yields of about 80% were obtained when the quantities of Rh(III) or Ir(III) cations and 16aneS4-diol ligand in the solutions were 62.5 nmol and 250 nmol, respectively, and the pH ranged 3.0–4.0. Syntheses required heating for 1–1.5 h at 75–80 °C. The influence of microwave heating on the time and completeness of the complexation reaction was evaluated and compared with the conventional method of heating in an oil bath. Microwave synthesis accelerates reactions significantly. With microwave heating, yields of about 75% for Rh[16aneS4-diol]131I and Ir[16aneS4-diol]131I complexes were obtained after only 20 min exposure of the reaction mixtures to microwave radiation. In conclusion, this study has shown that it is possible to attach an astatide anion to soft metal cations in a simple and fast one-step procedure, with high yields. These complexes will be evaluated as reagents for labeling biomolecules.Keywords
This publication has 39 references indexed in Scilit:
- Synthesis, radioiodination, and biodistribution of some nido- and closo-monocarbon carborane derivativesNuclear Medicine and Biology, 2004
- Reagents for Astatination of Biomolecules: Comparison of the in Vivo Distribution and Stability of Some Radioiodinated/Astatinated Benzamidyl andnido-Carboranyl CompoundsBioconjugate Chemistry, 2003
- Tissue distribution and radiation dosimetry of astatine-211-labeled chimeric 81C6, an α-particle-emitting immunoconjugateNuclear Medicine and Biology, 1997
- Biodistribution of model 105Rh-labeled tetradentate thiamacrocycles in ratsNuclear Medicine and Biology, 1997
- An Rh-105 complex of tetrathiacyclohexadecane diol with potential for formulating bifunctional chelatesNuclear Medicine and Biology, 1996
- Preparation and preliminary evaluation of 4-[211At]astato-N-piperidinoethyl benzamideNuclear Medicine and Biology, 1995
- Microwave‐facilitated synthesis of [18F]‐spiperoneJournal of Labelled Compounds and Radiopharmaceuticals, 1989
- N.C.A. radiofluorination of altanserine a potential serotonine receptor‐binding radiopharmaceutical for positron emission tomographyJournal of Labelled Compounds and Radiopharmaceuticals, 1989
- Cyclotron isotopes and radiopharmaceuticals—XXXV astatine-211The International Journal of Applied Radiation and Isotopes, 1985
- The nature of the astatine-protein bondThe International Journal of Applied Radiation and Isotopes, 1981