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Evaluation of (4-[18F]Fluorophenyl)triphenylphosphonium Ion. A Potential Myocardial Blood Flow Agent for PET

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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.

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Conflict of interest statement

Dr. Shoup has no conflict of interest. He is listed on the patent as an inventor and does not own any shares or options in FluoroPharma. Dr. Fischman has no conflict of interest. He is listed on the patent as an inventor and does not own any shares or options in FluoroPharma. Dr. Elmaleh has conflict of interest. He is the scientific founder of FluoroPharma and he is listed on the patent as an inventor and owns shares and options in FluoroPharma. Dr. Brownell has no conflict of interest. Dr. Zhu has no conflict of interest. Mr. Guerrero has no conflict of interest.

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Authors and Affiliations

  1. Department of Radiology, Massachusetts General Hospital, Edwards Building B015, 55 Fruit Street, Boston, MA, 02114, USA

    Timothy M. Shoup, David R. Elmaleh, Anna-Liisa Brownell, Aijun Zhu, J. Luis Guerrero & Alan J. Fischman

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  1. Timothy M. Shoup
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  2. David R. Elmaleh
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  3. Anna-Liisa Brownell
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  4. Aijun Zhu
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  5. J. Luis Guerrero
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  6. Alan J. Fischman
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Correspondence to David R. Elmaleh.

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Shoup, T.M., Elmaleh, D.R., Brownell, AL. et al. Evaluation of (4-[18F]Fluorophenyl)triphenylphosphonium Ion. A Potential Myocardial Blood Flow Agent for PET. Mol Imaging Biol 13, 511–517 (2011). https://doi.org/10.1007/s11307-010-0349-2

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  • DOI: https://doi.org/10.1007/s11307-010-0349-2

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