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

Introduction13C, 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.MethodsStudies 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 very low-density lipoprotein (VLDL), low-density lipoprotein (LDL) and high-density lipoprotein (HDL).ResultsMyocardial 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<.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<.001) into the range of established iodinated FA tracers. polyoxyethylene(20) sorbitan monooleate improved the heart-to-liver ratio in the biodistribution studies.ConclusionsMyocardial uptake of [99mTc]-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.