Mark M. Goodman

New radioiodinated methyl-branched fatty acids for cardiac studies

The effects of 3-methyl substitution on the heart retention and metabolism of 3-R,S-methyl-(BMIPP) and 3,3-dimethyl-(DMIPP) analogues of 15-(p-iodophenyl)-pentadecanoic acid (IPP) were studied in rats. Methyl substitution considerably increased the myocardial half-time values in fasted rats: IPP, 5–10 min; BMIPP, 30–45 min; DMIPP, 6–7 h. Because of the observed differences in the relative myocardial uptake and retention of these agents, an evaluation of the subcellular distribution profiles and the distribution of radioactivity within various lipid pools extracted from cell components was performed. Studies with DMIPP in food-deprived rats have shown high levels of the free fatty acid and only slow conversion to triglycerides. These data are in contrast to the rapid clearance of the straight chain IPP analogue and rapid incorporation into triglycerides, and suggest that the prolonged myocardial retention observed with DMIPP in vivo may result from inhibition of β oxidation. Subcellular distribution studies have shown predominant association of DMIPP and BMIPP with the mitochondrial and microsomal fractions, while IPP was primarily found in the cytoplasm. Because of the unique “trapping” properties and the high heart: blood ratios, [123I]DMIPP should be useful for evaluation of aberrations in regional myocardial uptake.

Evaluation of the metabolism in rat hearts of two new radioiodinated 3-methyl-branched fatty acid myocardial imaging agents.

The biological fate of two new radioiodinated 3-methyl-branched fatty acids has been evaluated in rat hearts following intravenous administration. Methylbranching was introduced in [15-(p-iodophenyl)-3-R,S-methylpentadecanoic acid (BMIPP) and 15-(p-iodophenyl)-3,3-dimethylpentadecanoic acid (DMIPP) to inhibit β-oxidation. The goals of these studies were to correlate the effects of methyl-branching on the incorporation of these agents into the various fatty acid pools and subcellular distribution profiles, and to relate these data to the myocardial retention properties. The properties of BMIPP and DMIPP were compared with the 15-(p-iodophenyl)pentadecanoic acid straight-chain analogue (IPP). Differences in the heart retention of the analogues after intravenous administration in rats correlated with differences observed in subcellular distribution patterns. The dimethyl DMIPP analogue showed the longest retention and the highest association with the mitochondrial and microsomal fractions (34%, 38%) 30 min after injection. These data are in contrast to the rapid clearance of the straight-chain IPP analogue which showed much lower relative association with the mitochondria and microsomes (18%, 15%). The distribution patterns of each analogue in the various lipid pools appeared consistent with the expected capacity of the analogues to be metabolized by β-oxidation. In contrast to the rapid oxidation of the straight-chain IPP analogue, the 3-monomethyl BMIPP analogue appeared to undergo slower oxidation and clearance, whereas the dimethyl-branched DMIPP analogue was apparently not catabolized by the myocardium. All three analogues showed some incorporation into triglycerides. The metabolism patterns of the branched analogues reported here may provide useful information in the description of the mechanisms by which BMIPP and DMIPP are retained in rat myocardium.

Structurally modified fatty acids - clinical potential as tracers of metabolism

AbstractRecently 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 (

Effect of 3-methyl-branching on the myocardial retention of radioiodinated 19-iodo-18-nonadecenoic acid analogues

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Studies of a new fatty acid analog (DMIVN) in hypertensive rats and the effect of verapamil using ARG microimaging

: 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 (

Structurally modified fatty acids: clinical potential as tracers of metabolism.

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