Mirtschink Peter, Stehr Sebastian N, Walther Martin, Pietzsch Jens, Bergmann Ralf, Pietzsch Hans-Jürgen, Weichsel Johannes, Pexa Annette, Dieterich Peter, Wunderlich Gerd, Binas Bert, Kropp Joachim, Deussen Andreas
Institute of Physiology, Technical University Dresden, 01307 Dresden, Germany.
Nucl Med Biol. 2009 Oct;36(7):833-43. doi: 10.1016/j.nucmedbio.2009.06.009.
(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.
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).
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 (99m)Tc-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.
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.
碳-13（¹³C）、氟-18（¹⁸F）和碘-123（¹²³I）脂肪酸（FA）用于心肌成像。最近，我们团队发现，[锝-99m（⁹⁹ᵐTc）]标记的“4 + 1”脂肪酸可被摄取到大鼠和豚鼠心肌中。本研究评估了这些脂肪酸衍生物心肌摄取和全身生物分布的决定因素。
对缺乏FAT/CD36的Wistar - Kyoto（WKY）大鼠和自发性高血压大鼠（SHR）的离体灌注心脏，以及心脏型脂肪酸结合蛋白基因敲除小鼠（H - FABP）（-/-）和H - FABP（+/ +）进行研究。应用8种4 + 1 - [锝-99m（⁹⁹ᵐTc）] - 脂肪酸3分钟，随后冲洗1分钟。使用数学模型分析脂肪酸动力学及与蛋白质的结合。在有和没有吐温80的大鼠中研究全身分布。用[锝-99m（⁹⁹ᵐTc）] - 脂肪酸进行的体外分级分离研究评估红细胞摄取以及与血浆脂蛋白极低密度脂蛋白（VLDL）、低密度脂蛋白（LDL）和高密度脂蛋白（HDL）的结合。
在离体WKY大鼠心脏中，心肌摄取量为注入剂量的19.0% - 33.0%，在SHR心脏中为15.2% - 26.4%。然而，H - FABP（-/-）显示示踪剂摄取显著降低[2.8±0.6%ID（注射剂量百分比）对17±2%ID，P <.001]。红细胞摄取（<1.2%ID）和掺入脂蛋白的量可忽略不计。锝-99m（⁹⁹ᵐTc）-脂肪酸与白蛋白孵育可降低心室摄取（P <.001），使其进入已确立的碘化脂肪酸示踪剂范围。在生物分布研究中，聚氧乙烯（20）山梨醇单油酸酯改善了心/肝比值。
[锝-99m（⁹⁹ᵐTc）] - 脂肪酸4 + 1衍生物的心肌摄取依赖于H - FABP。因此，这些物质可能提供一种新工具，用于特异性评估H - FABP的局部心肌变化。
