Radioiododestannylation: preparation of radioiodinated vinyl alcohols and selected evaluation in rats.
Radioiododestannylation has been employed to prepare a series of radioiodinated vinyl alcohols, two of which were evaluated for their tissue distribution in rats. The radioiodination method utilized tri-alkylstannylvinyl intermediates that can be prepared in good yields from 1,2-bis(tributylstannyl) ethylene and the appropriate ketones or by hydrostannation of the corresponding ethynyl alcohols. The radiolabeling proceeded at the no-carrier-added level to give, after HPLC separation, the desired products in 85-95% isolated yields. Tissue distribution studies in the rat indicated that the agents were rapidly extracted by the brain and then quickly cleared. No retention of activity was observed in the nonmetabolizing or nonexcretory organs. Chemically, the use of the E-tributylstannylvinyl lithium followed by radioiodination controlled stereochemistry and eliminated the separation of E- and Z-iodovinyl isomers. Biologically, the compounds behaved as neutral, diffusible and nonmetabolized radiotracers that may be used for the evaluation of cerebral blood flow, potentially with the short-lived radionuclide I-122 or other short-lived radiohalogens.
Department of Pharmaceutical Sciences, Northeastern University, Boston, MA 02115, USA.
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Hanson
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Franke
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Murphy
D000438:Alcohols / Q000138:chemical synthesis / Q000493:pharmacokinetics; D000818:Animals; D001842:Bone and Bones / Q000378:metabolism; D001921:Brain / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D005260:Female; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics*; D008168:Lung / Q000378:metabolism; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism; D009947:Organotin Compounds; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution; D014753:Vinyl Compounds / Q000138:chemical synthesis / Q000493:pharmacokinetics*
D000438:Alcohols; D007457:Iodine Radioisotopes; D009947:Organotin Compounds; D014753:Vinyl Compounds