Synthesis and radiolabelling of a fatty acid xanthate with [99mTcN]+2 core for its possible use in myocardial imaging

Full text: Free fatty acids circulate in the plasma bound to albumin and cross the myocardial cell membrane by passive diffusion. Once inside the cell, fatty acids can either back-diffuse or become activated by acyl-CoA synthetase. Once the latter step occurs, fatty acids become polar and are trapped inside the cell where they can either undergo beta-oxidation or be incorporated into the intracellular lipid pool. Currently 123I-iodophenylpentadecanoic acid is being used employing this mechanism for myocardial perfusion imaging. Because of the limited accessibility of 123I, search for a technetium analogue is on for a long time. In line with this idea we synthesized xanthate derivative of 15-hydroxypentadecanoic acid (HPDA). Overnight reaction of known amount of HPDA with excess of carbondisulphide in 1M sodium hydroxide solution resulted in the formation of xanthate of HPDA. Excess carbondisulphide was removed under vacuum and the crude product was used as such without further purification for the radiolabeling studies. The xanthate of the fatty acid was then labeled with [99mTcN]+2 intermediate. A brief protocol for the preparation of [99mTcN]+2 intermediate involved mixing 1 mL of freshly eluted sodium pertechnetate to a commercially available kit vial, vortexing the mixture for a minute and then incubating it for further 20 min. The [99mTcN]2+ intermediate was prepared in >95% yields and was characterized by TLC using ethanol:chloroform:toluene:0.5M ammonium acetate (6:3:3:0.5 v/v) as well as saline as developing solvents. Optimized protocol for the labeling of HPDA-xanthate involved mixing 5 mg of the xanthate in 0.5 mL of saline with 0.5 mL of freshly prepared [99mTcN]+2 intermediate and incubating the reaction mixture for 15 min. The pH of the reaction mixture was maintained above 9 to avoid decomposition of the xanthate. After 15 min the pH was brought 7. By Paper electrophoresis more than than 95% complexation was observed. Biological studies are yet to be carried out. (author)