title: Dosimetry of 64Cu-DOTA-AE105, a PET tracer for uPAR imaging.
abstract: (64)Cu-DOTA-AE105 is a novel positron emission tomography (PET) tracer specific to the human urokinase-type plasminogen activator receptor (uPAR). In preparation of using this tracer in humans, as a new promising method to distinguish between indolent and aggressive cancers, we have performed PET studies in mice to evaluate the in vivo biodistribution and estimate human dosimetry of (64)Cu-DOTA-AE105.
  
  
  METHODS
  Five mice received iv tail injection of (64)Cu-DOTA-AE105 and were PET/CT scanned 1, 4.5 and 22 h post injection. Volume-of-interest (VOI) were manually drawn on the following organs: heart, lung, liver, kidney, spleen, intestine, muscle, bone and bladder. The activity concentrations in the mentioned organs [%ID/g] were used for the dosimetry calculation. The %ID/g of each organ at 1, 4.5 and 22 h was scaled to human value based on a difference between organ and body weights. The scaled values were then exported to OLINDA software for computation of the human absorbed doses. The residence times as well as effective dose equivalent for male and female could be obtained for each organ. To validate this approach, of human projection using mouse data, five mice received iv tail injection of another (64)Cu-DOTA peptide-based tracer, (64)Cu-DOTA-TATE, and underwent same procedure as just described. The human dosimetry estimates were then compared with observed human dosimetry estimate recently found in a first-in-man study using (64)Cu-DOTA-TATE.
  
  
  RESULTS
  Human estimates of (64)Cu-DOTA-AE105 revealed the heart wall to receive the highest dose (0.0918 mSv/MBq) followed by the liver (0.0815 mSv/MBq), All other organs/tissue were estimated to receive doses in the range of 0.02-0.04 mSv/MBq. The mean effective whole-body dose of (64)Cu-DOTA-AE105 was estimated to be 0.0317 mSv/MBq. Relatively good correlation between human predicted and observed dosimetry estimates for (64)Cu-DOTA-TATE was found. Importantly, the effective whole body dose was predicted with very high precision (predicted value: 0.0252 mSv/Mbq, Observed value: 0.0315 mSv/MBq) thus validating our approach for human dosimetry estimation.
  
  
  CONCLUSIONS
  Favorable dosimetry estimates together with previously reported uPAR PET data fully support human testing of (64)Cu-DOTA-AE105.
authors.affiliation: The Danish-Chinese Center for Proteases and Cancer; Department of Clinical Physiology, Nuclear Medicine & PET, Center for Diagnostic Investigations, Rigshospitalet, Copenhagen, Denmark; Cluster for Molecular Imaging, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Morten
authors.initials: M
authors.lastname: Persson
authors.affiliation: Department of Clinical Physiology, Nuclear Medicine & PET, Center for Diagnostic Investigations, Rigshospitalet, Copenhagen, Denmark; Cluster for Molecular Imaging, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Henrik H
authors.initials: HH
authors.lastname: El Ali
authors.affiliation: Department of Clinical Physiology, Nuclear Medicine & PET, Center for Diagnostic Investigations, Rigshospitalet, Copenhagen, Denmark; Cluster for Molecular Imaging, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Tina
authors.initials: T
authors.lastname: Binderup
authors.affiliation: Department of Clinical Physiology, Nuclear Medicine & PET, Center for Diagnostic Investigations, Rigshospitalet, Copenhagen, Denmark; Cluster for Molecular Imaging, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Andreas
authors.initials: A
authors.lastname: Pfeifer
authors.affiliation: Department of Clinical Physiology, Nuclear Medicine & PET, Center for Diagnostic Investigations, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Jacob
authors.initials: J
authors.lastname: Madsen
authors.affiliation: Hevesy Laboratory, DTU Nutech, Technical University of Denmark, Kongens Lyngby, Denmark.
authors.forename: Palle
authors.initials: P
authors.lastname: Rasmussen
authors.affiliation: The Danish-Chinese Center for Proteases and Cancer; Department of Clinical Physiology, Nuclear Medicine & PET, Center for Diagnostic Investigations, Rigshospitalet, Copenhagen, Denmark; Cluster for Molecular Imaging, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark. Electronic address: akjaer@sund.ku.dk.
authors.forename: Andreas
authors.initials: A
authors.lastname: Kjaer
mesh_terms: D000818:Animals; D003301:Copper Radioisotopes; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D010455:Peptides / Q000737:chemistry* / Q000493:pharmacokinetics; D049268:Positron-Emission Tomography / Q000379:methods*; D011849:Radioactive Tracers; D011874:Radiometry; D055293:Receptors, Urokinase Plasminogen Activator / Q000378:metabolism*
chemical_list: D003301:Copper Radioisotopes; D010455:Peptides; D011849:Radioactive Tracers; D055293:Receptors, Urokinase Plasminogen Activator
keywords: DOTA; Dosimetry; PET; Peptide; Translational; Urokinase; uPAR