title: Comparison of 18F-Labeled Fluoroalkylphosphonium Cations with 13N-NH3 for PET Myocardial Perfusion Imaging.
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 (0.5 mL/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 (0-10 min, P=0.027).
  
  
  CONCLUSIONS
  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, 18F-FATPs are promising new PET radiopharmaceuticals for myocardial perfusion imaging.
authors.affiliation: Department of Nuclear Medicine, Chonnam National University Hwasun Hospital, Hwasun, Korea; and.
authors.forename: Dong-Yeon
authors.initials: DY
authors.lastname: Kim
authors.affiliation: Department of Nuclear Medicine, Chonnam National University Hwasun Hospital, Hwasun, Korea; and.
authors.forename: Hyeon Sik
authors.initials: HS
authors.lastname: Kim
authors.affiliation: Department of Nuclear Medicine, Klinikum Rechts der Isar, Technische Universität München, Munich, Germany.
authors.forename: Sybille
authors.initials: S
authors.lastname: Reder
authors.affiliation: Department of Nuclear Medicine, Chonnam National University Hwasun Hospital, Hwasun, Korea; and.
authors.forename: Jin Hai
authors.initials: JH
authors.lastname: Zheng
authors.affiliation: Department of Nuclear Medicine, Klinikum Rechts der Isar, Technische Universität München, Munich, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Herz
authors.affiliation: Department of Nuclear Medicine, Klinikum Rechts der Isar, Technische Universität München, Munich, Germany.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Higuchi
authors.affiliation: Department of Nuclear Medicine, Chonnam National University Hwasun Hospital, Hwasun, Korea; and.
authors.forename: A Young
authors.initials: AY
authors.lastname: Pyo
authors.affiliation: Department of Nuclear Medicine, Chonnam National University Hwasun Hospital, Hwasun, Korea; and.
authors.forename: Hee-Seung
authors.initials: HS
authors.lastname: Bom
authors.affiliation: Department of Nuclear Medicine, Klinikum Rechts der Isar, Technische Universität München, Munich, Germany jjmin@jnu.ac.kr markus.schwaiger@tum.de.
authors.forename: Markus
authors.initials: M
authors.lastname: Schwaiger
authors.affiliation: Department of Nuclear Medicine, Chonnam National University Hwasun Hospital, Hwasun, Korea; and jjmin@jnu.ac.kr markus.schwaiger@tum.de.
authors.forename: Jung-Joon
authors.initials: JJ
authors.lastname: Min
mesh_terms: D000641:Ammonia; D000818:Animals; D005462:Fluorine Radioisotopes; D006321:Heart / Q000000981:diagnostic imaging*; D007091:Image Processing, Computer-Assisted; D008099:Liver / Q000000981:diagnostic imaging / Q000378:metabolism; D009203:Myocardial Infarction / Q000000981:diagnostic imaging; D055414:Myocardial Perfusion Imaging / Q000379:methods*; D009206:Myocardium / Q000378:metabolism; D009590:Nitrogen Radioisotopes; D009943:Organophosphorus Compounds; D049268:Positron-Emission Tomography / Q000379:methods*; D019275:Radiopharmaceuticals; D051381:Rats
chemical_list: D005462:Fluorine Radioisotopes; D009590:Nitrogen Radioisotopes; D009943:Organophosphorus Compounds; D019275:Radiopharmaceuticals; D000641:Ammonia
keywords: 18F-fluoroalkylphosphonium cations; cardiac PET; first-pass extraction fraction; myocardial infarction; perfusion