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Validation of 99mTc-labeled "4+1" fatty acids for myocardial metabolism and flow imaging Part 1: Myocardial extraction and biodistribution
Mirtschink, P.; Stehr, S. N.; Walther, M.; Pietzsch, J.; Bergmann, R.; Pietzsch, H.-J.; Weichsel, J.; Pexa, A.; Dieterich, P.; Wunderlich, G.; Binas, B.; Kropp, J.; Deussen, A.;
13C, 18F and 123I fatty acids (FA) are used for myocardial imaging. Recently, our group showed that 99mTc-labeled "4+1" FA are extracted into the rat and guinea pig myocardium. The present study evaluates determinants of myocardial uptake and whole body biodistribution of these FA derivatives. Studies were performed with isolated perfused hearts of Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR) with a FAT/CD36 deficiency, as well as with heart type FA binding protein knockout mice (H-FABP-/-) and H-FABP+/+. Eight "4+1"-99mTc- FA were applied for 3 min followed by 1 min washout. A mathematical model was used to analyze FA dynamics and binding to proteins. Whole body distribution was studied in rats with and without Tween 80. In vitro fractionation studies with 99mTc- FA assessed red blood cell uptake as well as association with plasma lipoproteins (VLDL, LDL and HDL). Myocardial extraction was 19.0-33.0 % of the infused dose in isolated WKY and 15.2-26.4 % in SHR hearts. However, H-FABP-/- showed a marked reduction of tracer extraction (2.8 ± 0.6%ID vs. 17 ± 2%ID P < 0.001). Uptake in red blood cells (< 1.2%ID) and incorporation into lipoproteins were negligible. Incubation of 99mTc-FA with albumin reduced ventricular extraction (P < 0.001) into the range of established iodinated FA tracers. Tween 80 improved the heart-to-liver ratio in the biodistribution studies. Myocardial uptake of "4+1"-99mTc- FA derivatives is dependent on H-FABP. These substances may therefore provide a new tool to specifically assess regional myocardial changes of H-FABP.
Keywords: Technetium fatty acid; isolated heart; H-FABP; CD36; myocardial imaging

Publ.-Id: 11893 - Permalink