title: Pharmacokinetic Analysis of (64)Cu-ATSM Dynamic PET in Human Xenograft Tumors in Mice.
abstract: The aim of this study was to evaluate the feasibility to perform voxel-wise kinetic modeling on datasets obtained from tumor-bearing mice that underwent dynamic PET scans with (64)Cu-ATSM and extract useful physiological parameters.
  
  
  METHODS
  Tumor-bearing mice underwent 90-min dynamic PET scans with (64)Cu-ATSM and CT scans with contrast. Irreversible and reversible two-tissue compartment models were fitted to time activity curves (TACs) obtained from whole tumor volumes and compared using the Akaike information criterion (AIC). Based on voxel-wise pharmacokinetic analysis, parametric maps of model rate constants k₁, k₃ and Ki were generated and compared to (64)Cu-ATSM uptake.
  
  
  RESULTS
  Based on the AIC, an irreversible two-tissue compartment model was selected for voxel-wise pharmacokinetic analysis. Of the extracted parameters, k₁ (~perfusion) showed a strong correlation with early tracer uptake (mean spearman R = 0.88) 5 min post injection (pi). Moreover, positive relationships were found between late tracer uptake (90 min pi) and both k₃ and the net influx rate constant, Ki (mean spearman R = 0.56 and R = 0.86; respectively).
  
  
  CONCLUSIONS
  This study shows the feasibility to extract relevant parameters from voxel-wise pharmacokinetic analysis to be used for preclinical validation of (64)Cu-ATSM as a hypoxia-specific PET tracer.
authors: Cluster for Molecular Imaging, Faculty of Health Sciences, University of Copenhagen, Blegdamsvej 3, 2200 Copenhagen, Denmark. fanli@sund.ku.dk.|Department of Clinical Physiology, Nuclear Medicine & PET, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, 2100 Copenhagen, Denmark. fanli@sund.ku.dk.
authors: Fan
authors: F
authors: Li
authors: Cluster for Molecular Imaging, Faculty of Health Sciences, University of Copenhagen, Blegdamsvej 3, 2200 Copenhagen, Denmark. jtran@sund.ku.dk.|Department of Clinical Physiology, Nuclear Medicine & PET, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, 2100 Copenhagen, Denmark. jtran@sund.ku.dk.
authors: Jesper Tranekjær
authors: JT
authors: Jørgensen
authors: Department of Clinical Physiology, Nuclear Medicine & PET, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, 2100 Copenhagen, Denmark. Jacob.Madsen@regionh.dk.
authors: Jacob
authors: J
authors: Madsen
authors: Cluster for Molecular Imaging, Faculty of Health Sciences, University of Copenhagen, Blegdamsvej 3, 2200 Copenhagen, Denmark. akjaer@sund.ku.dk.|Department of Clinical Physiology, Nuclear Medicine & PET, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, 2100 Copenhagen, Denmark. akjaer@sund.ku.dk.
authors: Andreas
authors: A
authors: Kjaer
keywords: 64Cu-ATSM; PET; PET/CT; cancer; hypoxia; kinetic modeling; parametric mapping; voxel-wise pharmacokinetic analysis; xenograft tumors