title: Biodistribution and radiation dosimetry of LMI1195: first-in-human study of a novel 18F-labeled tracer for imaging myocardial innervation.
abstract: A novel (18)F-labeled ligand for the norepinephrine transporter (N-[3-bromo-4-(3-(18)F-fluoro-propoxy)-benzyl]-guanidine [LMI1195]) is in clinical development for mapping cardiac nerve terminals in vivo using PET. Human safety, whole-organ biodistribution, and radiation dosimetry of LMI1195 were evaluated in a phase 1 clinical trial.
  
  
  METHODS
  Twelve healthy subjects at 3 clinical sites were injected intravenously with 150-250 MBq of LMI1195. Dynamic PET images were obtained over the heart for 10 min, followed by sequential whole-body images for approximately 5 h. Blood samples were obtained, and heart rate, electrocardiogram, and blood pressure were monitored before and during imaging. Residence times were determined from multiexponential regression of organ region-of-interest data normalized by administered activity (AA). Radiation dose estimates were calculated using OLINDA/EXM. Myocardial, lung, liver, and blood-pool standardized uptake values were determined at different time intervals.
  
  
  RESULTS
  No adverse events due to LMI1195 were seen. Blood radioactivity cleared quickly, whereas myocardial uptake remained stable and uniform throughout the heart over 4 h. Liver and lung activity cleared relatively rapidly, providing favorable target-to-background ratios for cardiac imaging. The urinary bladder demonstrated the largest peak uptake (18.3% AA), followed by the liver (15.5% AA). The mean effective dose was 0.026 ± 0.0012 mSv/MBq. Approximately 1.6% AA was seen in the myocardium initially, remaining above 1.5% AA (decay-corrected) through 4 h after injection. The myocardium-to-liver ratio was approximately unity initially, increasing to more than 2 at 4 h.
  
  
  CONCLUSIONS
  These preliminary data suggest that LMI1195 is well tolerated and yields a radiation dose comparable to that of other commonly used PET radiopharmaceuticals. The kinetics of myocardial and adjacent organ activity suggest that cardiac imaging should be possible with acceptable patient radiation dose.
authors.affiliation: Section of Cardiovascular Medicine, Department of Medicine, Yale University School of Medicine, New Haven, Connecticut Department of Diagnostic Radiology, Yale University School of Medicine, New Haven, Connecticut albert.sinusas@yale.edu.
authors.forename: Albert J
authors.initials: AJ
authors.lastname: Sinusas
authors.affiliation: Lantheus Medical Imaging, North Billerica, Massachusetts.
authors.forename: Joel
authors.initials: J
authors.lastname: Lazewatsky
authors.affiliation: Holy Name Medical Center, Teaneck, New Jersey.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Brunetti
authors.affiliation: Morristown Medical Center, Morristown, New Jersey; and.
authors.forename: Gary
authors.initials: G
authors.lastname: Heller
authors.affiliation: Section of Cardiovascular Medicine, Department of Medicine, Yale University School of Medicine, New Haven, Connecticut.
authors.forename: Ajay
authors.initials: A
authors.lastname: Srivastava
authors.affiliation: Section of Cardiovascular Medicine, Department of Medicine, Yale University School of Medicine, New Haven, Connecticut.
authors.forename: Yi-Hwa
authors.initials: YH
authors.lastname: Liu
authors.affiliation: CDE Dosimetry Services, Knoxville, Tennessee.
authors.forename: Richard
authors.initials: R
authors.lastname: Sparks
authors.affiliation: CDE Dosimetry Services, Knoxville, Tennessee.
authors.forename: Andrey
authors.initials: A
authors.lastname: Puretskiy
authors.affiliation: Department of Diagnostic Radiology, Yale University School of Medicine, New Haven, Connecticut.
authors.forename: Shu-fei
authors.initials: SF
authors.lastname: Lin
authors.affiliation: Lantheus Medical Imaging, North Billerica, Massachusetts.
authors.forename: Paul
authors.initials: P
authors.lastname: Crane
authors.affiliation: Department of Diagnostic Radiology, Yale University School of Medicine, New Haven, Connecticut.
authors.forename: Richard E
authors.initials: RE
authors.lastname: Carson
authors.affiliation: Lantheus Medical Imaging, North Billerica, Massachusetts.
authors.forename: L Veronica
authors.initials: LV
authors.lastname: Lee
mesh_terms: D000328:Adult; D005260:Female; D005462:Fluorine Radioisotopes; D005464:Fluorobenzenes / Q000493:pharmacokinetics; D006146:Guanidines / Q000493:pharmacokinetics; D006321:Heart / Q000000981:diagnostic imaging / Q000294:innervation*; D006801:Humans; D008297:Male; D011874:Radiometry; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals; D014018:Tissue Distribution
chemical_list: D005462:Fluorine Radioisotopes; D005464:Fluorobenzenes; D006146:Guanidines; D019275:Radiopharmaceuticals; C561360:flubrobenguane
keywords: biodistribution; dosimetry; myocardium; positron emission tomography; sympathetic imaging