Structurally modified fatty acids: Clinical potential as tracers of metabolism

Recently 15-p-iodophenyl-β-methyl-pentadecanoic acid (BMPPA) was proposed for use in myocardial scintigraphy, as a possible probe of metabolic processes other than β-oxidation. In 19 patients (CAD/15, St.p. Mi/7; control 4) myocardial scintigraphy was carried out after i.v. I-123-BMPPA (2–4 mCi). Data were collected (LAO 45°/14; anterior/5) for 100 min in the fasted patients. Organ to background (BG) ratios were calculated for the heart (H) and liver (L), and the elimination (E) behaviour was analyzed from BG (vena cava region) corrected time activity curves. In 10 patients plasma and urine were examined. By CHCl₃/MeOH extraction of plasma samples (90 min after injection), both in water and in organic medium soluble catabolites were found. TLC fractionation showed that those were co-migrating, compared to standards, with bencoic acid, BMPPA and trigylcerides. In the urine (0–2 h after injection, 4.1% dose) hippuric acid was found. The mean t-max of BMPPA occurred at 15 min in the heart and at 9 min in the liver (P<0.01), with H/BG and L/BG ratios of 1.8 and 2.1, respectively. The elimination of BMPPA was slower from the heart than from the liver (P<0.01). It was biexponential from the liver in all cases ( \(\bar x\) : t/2 I, 11.4 min; t/2 II, 92 min; t/2 I uncor., 38 min) with the size of phase I smaller than that of phase II ( \(\bar x\) : I/II, 0.57). From the heart BMPPA turnover was biexponential in 11 patients ( \(\bar x\) : t/2 I, 13.8 min; t/2 II, 187 min; t/2 I uncor., 65 min; I/II, 0.34), but monoexponential in 8 ( \(\bar x\) : t/2, 218 min). In 13 diseased regions (MI/7) BMPPA uptake was reduced, and the E behaviour was mostly abnormal as compared to the respective undiseased region. We conclude that BMPPA is a useful agent for myocardial scintigraphy. Its longer retention time in the heart compared to unbranched radioiodinated fatty acids may facilitate SPECT studies. E behaviour and plasma analysis indicate that BMPPA is metabolically broken down. Yet, the complexity of the supposed mechanism may impede curve interpretation in terms of specific metabolic pathways.