Preparation and evaluation of 3-methyl isomers of 15-(p-iodophenyl)-3-methylpentadecanoic acid (BMIPP): 3R-BMIPP shows greater heart uptake than 3S-BMIPP in rats
- Oak Ridge National Lab., TN (United States); and others
Iodine-123 racemic (3-R,S) BMIPP is of widespread interest for evaluation of myocardial viability. To evaluate the effects of the asymmetric C-3 center of BMIPP on heart uptake/clearance we have resolved and characterized 3R- and 3S-BMIPP (H-1 and C-13 NMR, MS, HPLC, [{alpha}], m.p.) and evaluated the radioiodinated isomers in rats. A thiophene {open_quotes}template{close_quotes} approach using ethyl 3R-methylglutarate was used to synthesize the authentic 3R-BMPPA substrate (mp 41-42 {degrees}C, [{alpha}] + 1.45 {degrees}). Reaction of racemic 3-R, S-BNPPA with S-(-)-{alpha}-methylbenzylamine gave the diastereomeric amides, separated by TLC, column or HPLC. The more polar isomer was identical to the amide prepared from the 3R-isomer. HCI cleavage of the purified diastereomers provided 3R- and 3S-BMPPA (mp 40-41 {degrees}C, [{alpha}] - 3.90 {degrees}). Iodination (TTFAA/KI) gave 3R-BMIPP (mp 51-52 {degrees}C, [{alpha}] + 0.74 {degrees}) and 3S-BMIPP (mp 45-46 {degrees}C, [{alpha}] - 1.67 {degrees}), which formed amides identical with the two amides separated from the 3-R, S-BMIPP amide mixture. A [I-125]-3R-BMIPP and [I-131]-3S-BMIPP mixture was administered to groups of fasted rats (n = 5/group) sacrificed at 5, 15, 60 and 180 minutes. While blood levels and uptake and clearance from liver, lungs and kidney were nearly identical for both isomers, 3R-BMIPP had higher heart uptake at all periods evaluated (%ID/gram, i.e., 15 min: 3R = 5.25 {plus_minus} 0.77, 3S= 4.51 {plus_minus} 0.50; 180 min: 3R = 2.31 {plus_minus} 0.51, 3S = 1.98 {plus_minus} 0.26), suggesting that transport into the myocytes is different for the isomers. Higher heart uptake suggests that the 3R-BMIPP isomer should be further evaluated.
- DOE Contract Number:
- AC05-96OR22464
- OSTI ID:
- 447721
- Report Number(s):
- CONF-960659--
- Journal Information:
- Journal of Nuclear Medicine, Journal Name: Journal of Nuclear Medicine Journal Issue: Suppl.5 Vol. 37; ISSN JNMEAQ; ISSN 0161-5505
- Country of Publication:
- United States
- Language:
- English
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