Comparison of 18F-labeled fluoroalkylphosphonium cations with 13N-NH3 for PET myocardial perfusion imaging

Dong Yeon Kim, Hyeon Sik Kim, Sybille Reder, Jin Hai Zheng, Michael Herz, Takahiro Higuchi, Ayoung Pyo, Hee Seung Bom, Markus Schwaiger, Jung Joon Min

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Abstract

Despite substantial advances in the diagnosis of cardiovascular disease, there is a need for 18F-labeled myocardial perfusion agents for the diagnosis of ischemic heart disease because current PET tracers for myocardial perfusion imaging have a short half-life that limits their widespread clinical use in PET. Thus, 18F-labeled fluoroalkylphosphonium derivatives (18F-FATPs), including (5-18F-fluoropentyl)triphenylphosphonium cation (18F-FPTP), (6-18F-fluorohexyl)triphenylphosphonium cation (18F-FHTP), and (2-(2-18F-fluoroethoxy)ethyl)triphenylphosphonium cation (18F-FETP), were synthesized. The myocardial extraction and image quality of the 18F-FATPs were compared with those of 13N-NH3 in rat models. Methods: The first-pass extraction fraction (EF) values of the 18F-FATPs (18F-FPTP, 18F-FHTP, 18F-FETP) and 13N-NH3 were measured in isolated rat hearts perfused with the Langendorff method (flow velocities, 0.5, 4.0, 8.0, and 16.0 mL/min). Normal and myocardial infarction rats were imaged with small-animal PET after intravenous injection of 37 MBq of 18F-FATPs and 13N-NH3. To determine pharmacokinetics, a region of interest was drawn around the heart, and time-activity curves of the 18F-FATPs and 13N-NH3 were generated to obtain the counts per pixel per second. Defect size was analyzed on the basis of polar map images of 18F-FATPs and 13N-NH3. Results: The EF values of 18F-FATPs and 13N-NH3 were comparable at low flow velocity (0.5mL/min), whereas at higher flows EF values of 18F-FATPs were significantly higher than those of 13N-NH3 (4.0, 8.0, and 16.0 mL/min, P, 0.05). Myocardium-to-liver ratios of 18F-FPTP, 18F-FHTP, 18F-FETP, and 13N-NH3 were 2.10 ± 0.30, 4.36 ± 0.20, 3.88 ± 1.03, and 0.70 ± 0.09, respectively, 10 min after injection, whereas myocardium-to-lung ratios were 5.00 ± 0.25, 4.33 ± 0.20, 7.98 ± 1.23, and 2.26 ± 0.14, respectively. Although 18F-FATPs and 13N-NH3 sharply delineated myocardial perfusion defects, defect size on the 13N-NH3 images was significantly smaller than on the 18F-FATP images soon after tracer injection (0-10min, P 5 0.027). Conclusion: 18F-FATPs exhibit higher EF values and more rapid clearance from the liver and lung than 13N-NH3 in normal rats, which led to excellent image quality in a rat model of coronary occlusion. Therefore, 18FFATPs are promising new PET radiopharmaceuticals for myocardial perfusion imaging.

Original languageEnglish
Pages (from-to)1581-1586
Number of pages6
JournalJournal of Nuclear Medicine
Volume56
Issue number10
DOIs
Publication statusPublished - Oct 1 2015

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Keywords

  • Cardiac PET
  • F-fluoroalkylphosphonium cations
  • Firstpass extraction fraction
  • Myocardial infarction
  • Perfusion

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

Cite this

Kim, D. Y., Kim, H. S., Reder, S., Zheng, J. H., Herz, M., Higuchi, T., Pyo, A., Bom, H. S., Schwaiger, M., & Min, J. J. (2015). Comparison of 18F-labeled fluoroalkylphosphonium cations with 13N-NH3 for PET myocardial perfusion imaging. Journal of Nuclear Medicine, 56(10), 1581-1586. https://doi.org/10.2967/jnumed.115.156794