Synthesis, characterisation, and biodistribution of radioiodinated C-hydroxy-carboranes.
The synthesis, radiolabelling and biodistribution of iodinated C-hydroxy-nido-carborane ligands is described. Microwave heating by using NaF in aqueous ethanol was used to prepare {sodium [7-hydroxy-7,8-dicarba-nido-undecaborate], nido-carboranol} and {sodium [7-hydroxy-7,8-dicarba-nido-undecaborate-8-carboxylic acid], nido-salborin} in 97 and 90 % yield, respectively. Radioiodination of these nido-carboranes was completed by using both (125)I and (123)I, and the products were obtained in high radiochemical purity (>99 %) and yield (72 to 87 %). The structures of the radiolabelled products were validated through comparison to authentic standards. Biodistribution studies in BALB/c mice showed low accumulation of the labelled compounds in the liver and intestines, which are sites where labelled carboranes typically localise. The labelled cluster bearing hydroxy and carboxylic acid groups on the two carbon vertices demonstrated preferential clearance through the kidneys and low thyroid uptake. This compound had substantially reduced non-specific binding than the deshydroxy analogue making it an attractive bifunctional ligand for preparing targeted molecular imaging and therapy agents.
Department of Chemistry and Chemical Biology, McMaster University, Hamilton, Ontario, Canada.
Mohamed E
ME
El-Zaria
Nancy
N
Janzen
Megan
M
Blacker
John F
JF
Valliant
D000818:Animals; D001880:Boranes / Q000138:chemical synthesis* / Q000493:pharmacokinetics*; D002264:Carboxylic Acids / Q000737:chemistry*; D003952:Diagnostic Imaging; D005260:Female; D007422:Intestines / Q000000981:diagnostic imaging; D007457:Iodine Radioisotopes / Q000737:chemistry*; D007553:Isotope Labeling; D007668:Kidney / Q000000981:diagnostic imaging; D008024:Ligands; D008099:Liver / Q000000981:diagnostic imaging; D051379:Mice; D008807:Mice, Inbred BALB C; D015394:Molecular Structure; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000493:pharmacokinetics*; D013961:Thyroid Gland / Q000000981:diagnostic imaging; D014018:Tissue Distribution
D001880:Boranes; D002264:Carboxylic Acids; D007457:Iodine Radioisotopes; D008024:Ligands; D019275:Radiopharmaceuticals