Validation of 99m Tc-labeled “4+1” fatty acids for myocardial metabolism and flow imaging Part 1: myocardial extraction and biodistribution Peter Mirtschink a, ⁎ ,1 , Sebastian N. Stehr b,1 , Martin Walther c , Jens Pietzsch c , Ralf Bergmann c , Hans-Jürgen Pietzsch c , Johannes Weichsel a , Annette Pexa a , Peter Dieterich a , Gerd Wunderlich d , Bert Binas e , Joachim Kropp f , Andreas Deussen a a Institute of Physiology, Technical University Dresden, 01307 Dresden, Germany b Department of Anesthesiology, Technical University Dresden, 01307 Dresden, Germany c Institute of Radiopharmacy, Forschungszentrum Dresden-Rossendorf, 01314 Dresden, Germany d Department of Nuclear Medicine, Technical University Dresden, 01307 Dresden, Germany e Department of Veterinary Pathobiology, Texas A&M University, College Station, TX 77843, USA f Department of Nuclear Medicine Carl-Thiem Hospital Cottbus, 03048 Cottbus, Germany Received 31 March 2009; received in revised form 12 June 2009; accepted 27 June 2009 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 Pb .001]. Uptake in red blood cells (b1.2% ID) and incorporation into lipoproteins were negligible. Incubation of 99m Tc-FAwith albumin reduced ventricular extraction (Pb .001) into the range of established iodinated FA tracers. polyoxyethylene(20) sorbitan monooleate improved the heart-to-liver ratio in the biodistribution studies. 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. © 2009 Elsevier Inc. All rights reserved. Keywords: Technetium fatty acid; isolated heart; H-FABP; CD36; myocardial imaging 1. Introduction In ischaemia, oxidation of fatty acids (FAs) is suppressed, and glycolysis and glycogen breakdown is used as an energy source [1]. Therefore, radiolabeled FA allows the assessment of viable myocardium by using single photon emission computed tomography offering a valuable diagnostic tool for ischemic heart disease [2]. In addition to global perfusion Available online at www.sciencedirect.com Nuclear Medicine and Biology 36 (2009) 833 – 843 www.elsevier.com/locate/nucmedbio ⁎ Corresponding author. Institute of Physiology, Medical Faculty Carl Gustav Carus, Technical University of Dresden, 01307 Dresden, Germany. Tel.: +49 351 458 6006; fax: +49 351 458 6030. E-mail address: peter_mirtschink@web.de (P. Mirtschink). 1 Both authors contributed equally to this work. 0969-8051/$ – see front matter © 2009 Elsevier Inc. All rights reserved. doi:10.1016/j.nucmedbio.2009.06.009