Timothy M Shoup1, David R Elmaleh2, Anna-Liisa Brownell1, Aijun Zhu1, J Luis Guerrero1, Alan J Fischman1. 1. Department of Radiology, Massachusetts General Hospital, Edwards Building B015, 55 Fruit Street, Boston, MA, 02114, USA. 2. Department of Radiology, Massachusetts General Hospital, Edwards Building B015, 55 Fruit Street, Boston, MA, 02114, USA. delmaleh@partners.org.
Abstract
PURPOSE: The lipophilic cationic compound, (4-[¹⁸F]fluorophenyl)triphenylphosphonium ion (¹⁸F-FTPP) was synthesized and evaluated as a potential positron emission tomography (PET) myocardial perfusion agent. PROCEDURE: ¹⁸F-FTPP was prepared from (4-nitrophenyl)triphenylphosphonium nitrate and ammonium [¹⁸F]fluoride by nucleophilic aromatic substitution and was purified by high performance 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 ¹⁸F-FTPP. In addition, microPET imaging in rabbits (three) was performed before and after occlusion of the left anterior descending (LAD) artery with ¹³NH₃ (111 MBq) and ¹⁸F-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 ¹⁸F-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 ¹³NH₃ and ¹⁸F-FTPP indicated similar distributions of the two tracers in both normal and altered blood flow regions. CONCLUSION: The excellent heart-to-blood ratio of ¹⁸F-FTPP and its correlation with ¹³NH₃ 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.
PURPOSE: The lipophilic cationic compound, (4-[¹⁸F]fluorophenyl)triphenylphosphonium ion (¹⁸F-FTPP) was synthesized and evaluated as a potential positron emission tomography (PET) myocardial perfusion agent. PROCEDURE: ¹⁸F-FTPP was prepared from (4-nitrophenyl)triphenylphosphonium nitrate and ammonium [¹⁸F]fluoride by nucleophilic aromatic substitution and was purified by high performance 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 ¹⁸F-FTPP. In addition, microPET imaging in rabbits (three) was performed before and after occlusion of the left anterior descending (LAD) artery with ¹³NH₃ (111 MBq) and ¹⁸F-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 ¹⁸F-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 ¹³NH₃ and ¹⁸F-FTPP indicated similar distributions of the two tracers in both normal and altered blood flow regions. CONCLUSION: The excellent heart-to-blood ratio of ¹⁸F-FTPP and its correlation with ¹³NH₃ 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.
Authors: Padmaja Yalamanchili; Eric Wexler; Megan Hayes; Ming Yu; Jody Bozek; Mikhail Kagan; Heike S Radeke; Michael Azure; Ajay Purohit; David S Casebier; Simon P Robinson Journal: J Nucl Cardiol Date: 2007-10-22 Impact factor: 5.952
Authors: I C Summerhayes; T J Lampidis; S D Bernal; J J Nadakavukaren; K K Nadakavukaren; E L Shepherd; L B Chen Journal: Proc Natl Acad Sci U S A Date: 1982-09 Impact factor: 11.205
Authors: Mark D Bartholomä; Huamei He; Christina A Pacak; Patricia Dunning; Frederic H Fahey; Francis X McGowan; Douglas B Cowan; S Ted Treves; Alan B Packard Journal: Nucl Med Biol Date: 2013-09-04 Impact factor: 2.408
Authors: Stuart P McCluskey; Anna Haslop; Christopher Coello; Roger N Gunn; Edward W Tate; Richard Southworth; Christophe Plisson; Nicholas J Long; Lisa A Wells Journal: J Nucl Med Date: 2019-05-30 Impact factor: 10.057
Authors: Mark D Bartholomä; Vijay Gottumukkala; Shaohui Zhang; Amanda Baker; Patricia Dunning; Frederic H Fahey; S Ted Treves; Alan B Packard Journal: J Med Chem Date: 2012-12-14 Impact factor: 7.446