Preparation and in vivo evaluation of radioiodinated closo-decaborate(2-) derivatives to identify structural components that provide low retention in tissues.
BACKGROUND
In vivo deastatination of (211)At-labeled biomolecules can severely limit their use in endoradiotherapy. Our studies have shown that the use of closo-decaborate(2-) moiety for (211)At-labeling of biomolecules provides high in vivo stability towards deastatination. However, data from those studies have also been suggestive that some astatinated closo-decaborate(2-) catabolites may be retained in tissues. In this study, we investigated the in vivo distributions of several structurally simple closo-decaborate(2-) derivatives to gain information on the effects of functional groups if catabolites are released into the blood system from the carrier biomolecule.


METHODS
Thirteen closo-decaborate(2-) derivatives were synthesized and radioiodinated for evaluation. Tissue concentrations of the radioiodinated compounds were obtained in groups of five mice at 1 and 4 h postinjection (pi). Dual-label ((125)I and (131)I) experiments permitted evaluation of two compounds in each set of mice.


RESULTS
All of the target compounds were readily synthesized. Radioiodination reactions were conducted with chloramine-T and Na[(125/131)I]I in water to give high yields (75-96%) of the desired compounds. Biodistribution data at 1 and 4 h pi (representing catabolites released into the blood system) showed small differences in tissue concentrations for some compounds, but large differences for others. The results indicate that formal (overall) charge on the compounds could not be used as a predictor of tissue localization or retention. However, derivatives containing carboxylate groups generally had lower tissue concentrations. Acid cleavable hydrazone functionalities appeared to be the best candidates for further study.


CONCLUSIONS
Further studies incorporating hydrazone functionalities into pendant groups for biomolecule radiohalogenation are warranted.
Department of Radiation Oncology, University of Washington, Seattle, WA 98105, USA. dswilbur@u.washington.edu
D Scott
DS
Wilbur
Ming-Kuan
MK
Chyan
Donald K
DK
Hamlin
Matthew A
MA
Perry
D000818:Animals; D001881:Borates / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics*; D001896:Boron Compounds / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics*; D054879:Halogenation; D007267:Injections; D007457:Iodine Radioisotopes / Q000737:chemistry; D008297:Male; D051379:Mice; D008819:Mice, Nude
D001881:Borates; D001896:Boron Compounds; D007457:Iodine Radioisotopes