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

Publikation: Beitrag in FachzeitschriftForschungsartikelBeigetragenBegutachtung

Beitragende

  • Peter Mirtschink - , Institut für Physiologie (Autor:in)
  • Sebastian N. Stehr - , Klinik und Poliklinik für Anästhesiologie und Intensivtherapie (Autor:in)
  • Martin Walther - , Helmholtz-Zentrum Dresden-Rossendorf (Autor:in)
  • Jens Pietzsch - , Helmholtz-Zentrum Dresden-Rossendorf (Autor:in)
  • Ralf Bergmann - , Helmholtz-Zentrum Dresden-Rossendorf (Autor:in)
  • Hans Jürgen Pietzsch - , Helmholtz-Zentrum Dresden-Rossendorf (Autor:in)
  • Johannes Weichsel - , Institut für Physiologie (Autor:in)
  • Annette Pexa - , Institut für Physiologie (Autor:in)
  • Peter Dieterich - , Institut für Physiologie (Autor:in)
  • Gerd Wunderlich - , Klinik und Poliklinik für Nuklearmedizin (Autor:in)
  • Bert Binas - , Texas A&M University (Autor:in)
  • Joachim Kropp - , Carl-Thiem-Klinikum Cottbus (Autor:in)
  • Andreas Deussen - , Institut für Physiologie (Autor:in)

Abstract

Introduction: 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. 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+1-99mTc-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). 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<.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. Conclusions: Myocardial 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.

Details

OriginalspracheEnglisch
Seiten (von - bis)833-843
Seitenumfang11
FachzeitschriftNuclear medicine and biology
Jahrgang36
Ausgabenummer7
PublikationsstatusVeröffentlicht - Okt. 2009
Peer-Review-StatusJa

Externe IDs

PubMed 19720295
ORCID /0000-0002-3564-0193/work/164197652

Schlagworte

Ziele für nachhaltige Entwicklung

Schlagwörter

  • CD36, H-FABP, isolated heart, myocardial imaging, Technetium fatty acid