B Academy of Molecular Imaging and Society for Molecular Imaging, 2010 Published Online: 19 June 2010 DOI: 10.1007/s11307-010-0349-2 Mol Imaging Biol (2011) 13:511Y517 RESEARCH ARTICLE Evaluation of (4-[ 18 F]Fluorophenyl) triphenylphosphonium Ion. A Potential Myocardial Blood Flow Agent for PET Timothy M. Shoup, David R. Elmaleh, Anna-Liisa Brownell, Aijun Zhu, J. Luis Guerrero, Alan J. Fischman Department of Radiology, Massachusetts General Hospital, Edwards Building B015, 55 Fruit Street, Boston, MA, 02114, USA Abstract Purpose: The lipophilic cationic compound, (4-[ 18 F]fluorophenyl)triphenylphosphonium ion ( 18 F- FTPP) was synthesized and evaluated as a potential positron emission tomography (PET) myocardial perfusion agent. Procedure: 18 F-FTPP was prepared from (4-nitrophenyl)triphenylphosphonium nitrate and ammonium [ 18 F]fluoride by nucleophilic aromatic substitution and was purified by high perform- ance liquid chromatography before use. Biodistribution studies were performed in rats at 5, 30, 60 min (five rats per time point). Three rats were evaluated by microPET imaging after injection of 18 F-FTPP. In addition, microPET imaging in rabbits (three) was performed before and after occlusion of the left anterior descending (LAD) artery with 13 NH 3 (111 MBq) and 18 F-FTPP (74 MBq). Results: Biodistribution data in rats showed rapid blood clearance and high levels of accumulation in the heart; 75:1 heart-to-blood ratio at 30 min. Uptake of radioactivity in the heart was 1.64% ID/G, 1.51% ID/g, and 1.57% ID/g at 5, 30, and 60 min. At 5, 30, and 60 min, lung activity was 0.69% ID/g, 0.03% ID/g, and 0.38% ID/g, and liver uptake was 0.34% ID/g, 0.18% ID/g, and 0.17% ID/g. Heart-to-lung ratios at 5, 30, and 60 min were 2, 5, and 4. Bone accumulation was minimal. MicroPET imaging in both rats and rabbits after injection of 18 F- FTPP demonstrated an initial spike of activity in the myocardium corresponding to blood flow followed by a plateau after 1 min. Region of interest analysis of microPET images of normal and LAD-occluded rabbits with 13 NH 3 and 18 F-FTPP indicated similar distributions of the two tracers in both normal and altered blood flow regions. Conclusion: The excellent heart-to-blood ratio of 18 F-FTPP and its correlation with 13 NH 3 distribution in normal and LAD-occluded rabbits suggest that this radiopharmaceutical may have potential as a PET agent for characterizing mitochondrial damage and/or myocardial blood flow. Key words: Myocardial perfusion agent, Positron emission tomography, 18 F, Tetraphenylphosphonium, Mitochondrial damage, membrane potential Introduction M yocardial perfusion imaging is the most widely used technique for identifying patients at risk of heart attack from coronary artery disease (CAD) and course of treatment. It can be used to detect areas of the heart muscle that have inadequate blood supply, quantify the extent of the heart muscle with a limited blood flow, provide information about the heart’s pumping function, assess the amount of scarring from a heart attack, and evaluate the results of coronary bypass surgery or angioplasty [1–5]. Myocardial perfusion is typically assessed using the single photon Correspondence to: David R. Elmaleh; e-mail: delmaleh@partners.org