Validation of 99mTc-labeled “4+1” fatty acids for myocardial metabolism and flow imaging: Part 1: myocardial extraction and biodistribution

Abstract Introduction 13 C, 18 F and 123 I fatty acids (FA) are used for myocardial imaging. Recently, our group showed that [ 99m Tc]-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. Methods 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- 99m Tc-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 [ 99m Tc]-FA assessed red blood cell uptake as well as association with plasma lipoproteins very low-density lipoprotein (VLDL), low-density lipoprotein (LDL) and high-density lipoprotein (HDL). Results 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 (percent injected dose) vs. 17±2%ID P 99m Tc-FA with albumin reduced ventricular extraction ( P Conclusions Myocardial uptake of [ 99m Tc]-FA 4+1 derivatives is dependent on H-FABP. These substances may therefore provide a new tool to specifically assess regional myocardial changes of H-FABP.