Intramyocardial fate of 15-p-iodophenyl-beta-methylpentadecanoic acid (IMPPA): is it a good tracer of fatty acid myocardial uptake?

Iodinated fatty acids (FAs) are now used in Nuclear Medicine to assess, by external detection, myocardial metabolism. Methylated FAs have been proposed as tracers of FA myocardial uptake. IMPPA is a new FA analogue in which a methyl group have been introduced in beta position to inhibit beta-oxidation and a terminal phenyl group prevents a possible omega oxidation. We have compared the intramyocardial behaviour of this FA with the 15-p-iodophenyl-pentadecanoic acid (IPPA), the straight chain analogue, and with the 15-phenyl-beta-methylpentadecanoic acid (MPPA), the 3 of them being labelled with C14 on the carboxyl group, in isolated rat hearts perfused in a recirculating system. When IMPPA is compared to IPPA (influence of the methyl group), we observe 1--an inhibition of beta-oxidation (no significant production of labelled CO2 and very low radioactivity in the aqueous phase) leading to a reduced uptake, 2--a lower radioactivity in the organic phase due to a hindrance to the esterification process both into TGs and PLs, the free FAs level being higher. When IMPPA is compared to MPPA (influence of the iodine atom), we observe 1--the same inhibition of beta-oxidation, 2 - a higher myocardial radioactivity due to a much higher level of free FAs, the esterification into TGs and PLs being reduced. This study with IMPPA indicates that it is taken up by the heart and trapped there, as it is not oxydized. This long retention time, apart from giving good scintigraphic images, should make IMPPA useful to study the regional myocardial uptake of FAs.