Synthesis and evaluation of radioiodinated terminal-substituted 5-iodo-(2-thienyl) fatty acids as new myocardial imaging agents

In order to evaluate the stability of radioiodide attached to the 5 position of thiophenes substituted at the 2-position with tissue-specific groups as new radiopharmaceuticals, two ¹²⁵I]iodothienyl-substituted long-chain fatty acids have been prepared and evaluated in rats. Radioiodide was introduced into the 5 position of 17-(2-thienyi)heptadecanoic acid and 13-(2-thienyl)tridecanoic acid by K-¹²⁵I treatment of their corresponding 5-bis-(trifluoroacetoxy)]thallium derivatives. Tissue distribution studies in rats with 17-5-¹²⁵I]iodo(2-thienyl)]heptadecanoic acid shows significant heart uptake and prolonged retention accompanied by in vivo deiod-ination and moderate blood levels. A comparison of the heart uptake of the 17 carbon fatty acid with a 13 carbon analogue, 13-5-¹³⁵I]iodo(2-thienyl)]tridecanoic acid, demonstrated a significantly greater myocardial uptake for the 17 carbon fatty acid than the 13 carbon analogue. These results suggest that the 5-iodothienyl moiety substituted at the terminal position of long chain fatty acids does not interfere with myocardial uptake and that such compounds may be of value as a new class of myocardial imaging agents.