Quantitative analysis of myocardial kinetics of 15-p-[iodine-125]iodophenylpentadecanoic acid

Myocardial extraction and the characteristic tissue clearance of radioactivity following bolus injections of a radioiodinated (¹²⁵I) long chain fatty acid (LCFA) analog 15-p-iodophenylpentadecanoic acid (IPPA) were examined in the isolated perfused working rat heart. Radioactivity remaining in the heart was monitored with external scintillation probes. A compartmental model which included nonesterified tracer, catabolite, and complex lipid compartments successfully fitted tissue time-radioactivity residue curves, and gave a value for the rate of IPPA oxidation 1.8 times that obtained from steady-state release of tritiated water from labeled palmitic acid. The technique was sensitive to the impairment of LCFA oxidation in hearts of animals treated with the carnitine palmitoyltransferase I inhibitor, 2[5-(4-chlorophenyl)pentyl]oxirane-2-carboxylate (POCA). IPPA or similar modified fatty acids may be better than ¹¹C-labeled physiological fatty acids such as palmitate in this type of study, because efflux of unoxidized tracer and catabolite(s) from the heart are kinetically more distinct, and their contributions to the early data can be reliably separated. This technique may be suitable for extension to in vivo measurements with positron tomography and appropriate modified fatty acids.