| Online-Ressource |
Verfasst von: | Eisenhut, Michael [VerfasserIn]  |
| Lehmann, Wolf-Dieter [VerfasserIn]  |
| Hull, William Edmund [VerfasserIn]  |
| Just, Wilhelm W. [VerfasserIn]  |
| Hoffend, Johannes [VerfasserIn]  |
| Zehelein, Jörg [VerfasserIn]  |
| Zimmermann, Rainer [VerfasserIn]  |
Titel: | Trapping and metabolism of radioiodinated PHIPA 3-10 in the rat myocardium |
Verf.angabe: | Michael Eisenhut, Wolf D. Lehmann, William E. Hull, Wilhelm W. Just, Johannes Hoffend, Jörg Zehelein, Rainer Zimmermann |
E-Jahr: | 1997 |
Jahr: | December 1997 |
Umfang: | 6 S. |
Fussnoten: | Gesehen am 09.12.2024 |
Titel Quelle: | Enthalten in: Journal of nuclear medicine |
Ort Quelle: | New York, NY : Soc., 1964 |
Jahr Quelle: | 1997 |
Band/Heft Quelle: | 38(1997), 12, Seite 1864-1869 |
ISSN Quelle: | 2159-662X |
| 1535-5667 |
Abstract: | <p>PHIPA 3-10 [13-(49-iodophenyl)-3-(p-phenylene)tridecanoic acid] is a p-phenylene-bridged, radioiodinated ω-phenyl fatty acid that has recently been developed to study coronary artery disease or cardiomyopathies. Here, we demonstrate that PHIPA 3-10 exhibits the characteristics of a long-chain fatty acid, including its ability to be efficiently taken up by myocytes and to function as a substrate for beta-oxidation before it is trapped. <b>Methods:</b> Myocardial metabolism of carrier-added and carrier-free <sup>131</sup>I-PHIPA 3-10 preparations were investigated in rats in vivo and in isolated Langendorff rat hearts. Heart extracts were analyzed by high-performance liquid chromatography, negative-ion electrospray mass spectrometry and investigation of intracellular distribution using density-gradient centrifugation. <b>Results:</b> A single, rapidly formed metabolite was found in the heart extract and also, surprisingly, in the hydrolyzed lipids. The total amount of metabolite increased from 43% to 51% between 15 and 60 min postinjection. By high-performance liquid chromatography comparison with synthetic potential catabolites, the metabolite was assigned the namFXA 1-10 [11-(49-iodophe-nyl)-1-(p-phenylene)undecanoic acid] and was the product of one beta-oxidation cycle. Additional proof was obtained from the mass spectrometric analysis of the metabolite formed in vivo. The formation of this metabolite could be suppressed by Etomoxir, a carnitine palmitoyl transferase I inhibitor, indicating beta-oxidation of <sup>131</sup>I-PHIPA 3-10 in mitochondria. Final evidence for the involvement of mitochondria in the degradation of <sup>131</sup>I-PHIPA 3-10 was obtained by density-gradient centrifugation of homogenized rat heart tissue. The position of the labeled free PHIPA 3-10 and free metabolite peaked within the fraction containing mainly mitochondria. <b>Conclusion:</b> In spite of its bulky structure, <sup>131</sup>I-PHIPA 3-10 is extracted by the myocardium in a manner similar to the extraction of the unmodified fatty acid analog, IPPA. The retention of PHIPA 3-10 in heart muscle results from the presence of the p-phenylene group, which prevents more than one beta-oxidation cycle. Intracellular free PHIPA 3-10 and free PHIPA 1-10 are present in the mitochondria, whereas most of the esterified metabolite was found in the cytosolic lipid pool. Hence, the rapid appearance of PHIPA 1-10 in the lipid pool must be accounted for by mitochondrial leakage or by an unknown in-out transport system. </p> |
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Volltext: https://jnm.snmjournals.org/content/38/12/1864 |
Datenträger: | Online-Ressource |
Sprache: | eng |
K10plus-PPN: | 1911215892 |
Verknüpfungen: | → Zeitschrift |
Trapping and metabolism of radioiodinated PHIPA 3-10 in the rat myocardium / Eisenhut, Michael [VerfasserIn]; December 1997 (Online-Ressource)