title: Phase I, first-in-human study of BMS747158, a novel 18F-labeled tracer for myocardial perfusion PET: dosimetry, biodistribution, safety, and imaging characteristics after a single injection at rest.
abstract: (18)F-labeled BMS747158 is a novel myocardial perfusion imaging tracer that targets mitochondrial complex 1. The objectives of this phase I study were to evaluate radiation dosimetry, biodistribution, human safety, tolerability, and early elimination of (18)F activity in urine after injection of a single dose of the tracer at rest in healthy subjects.
  
  
  METHODS
  Thirteen healthy subjects were injected with 170-244 MBq (4.6-6.6 mCi) of BMS747158 intravenously. Dynamic PET was obtained over the heart for 10 min, followed by sequential whole-body imaging for 5 h. Blood samples and urinary excretion were collected for up to 8 h. Heart rate, electrocardiogram, and blood pressure were monitored before and during imaging. The residence times were determined from multiexponential regression of organ region-of-interest data normalized by injected dose. Absorbed dose estimates for all target organs were determined using MIRD schema with OLINDA/EXM software.
  
  
  RESULTS
  The organ receiving the largest mean absorbed dose was the kidneys at 0.066 mSv/MBq (0.24 rem/mCi), followed by the heart wall at 0.048 mSv/MBq (0.18 rem/mCi). The mean effective dose was 0.019 mSv/MBq (0.072 rem/mCi). The heart exhibited high and sustained retention of BMS747158 from the earliest images through approximately 5 h after injection. There were no drug-related adverse events, and the tracer was well tolerated in all subjects. Mean urinary excretion was 4.83 percentage injected dose (range, 0.64-12.41 percentage injected dose).
  
  
  CONCLUSIONS
  These preliminary data suggest that (18)F-labeled BMS747158 appears to be well tolerated and has a unique potential for myocardial perfusion PET.
authors.affiliation: Department of Molecular and Medical Pharmacology Nuclear Medicine, David Geffen School of Medicine at University of California, Los Angeles, California 90095-7064, USA. jmaddahi@mednet.ucla.edu
authors.forename: Jamshid
authors.initials: J
authors.lastname: Maddahi
authors.forename: Johannes
authors.initials: J
authors.lastname: Czernin
authors.forename: Joel
authors.initials: J
authors.lastname: Lazewatsky
authors.forename: Sung-Cheng
authors.initials: SC
authors.lastname: Huang
authors.forename: Magnus
authors.initials: M
authors.lastname: Dahlbom
authors.forename: Heinrich
authors.initials: H
authors.lastname: Schelbert
authors.forename: Richard
authors.initials: R
authors.lastname: Sparks
authors.forename: Alexander
authors.initials: A
authors.lastname: Ehlgen
authors.forename: Paul
authors.initials: P
authors.lastname: Crane
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhu
authors.forename: Marybeth
authors.initials: M
authors.lastname: Devine
authors.forename: Michael
authors.initials: M
authors.lastname: Phelps
mesh_terms: D000293:Adolescent; D000328:Adult; D000465:Algorithms; D003326:Coronary Circulation / Q000502:physiology*; D004569:Electroencephalography; D005260:Female; D005462:Fluorine Radioisotopes / Q000652:urine; D006321:Heart / Q000000981:diagnostic imaging*; D006801:Humans; D008297:Male; D049268:Positron-Emission Tomography; D011724:Pyridazines / Q000008:administration & dosage / Q000493:pharmacokinetics; D011874:Radiometry; D019275:Radiopharmaceuticals / Q000008:administration & dosage / Q000493:pharmacokinetics; D014018:Tissue Distribution; D014915:Whole-Body Counting; D055815:Young Adult
chemical_list: C525920:BMS 747158-02; D005462:Fluorine Radioisotopes; D011724:Pyridazines; D019275:Radiopharmaceuticals