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Diagnostics 2015, 5(2), 96-112; doi:10.3390/diagnostics5020096

Pharmacokinetic Analysis of 64Cu-ATSM Dynamic PET in Human Xenograft Tumors in Mice

1
Cluster for Molecular Imaging, Faculty of Health Sciences, University of Copenhagen, Blegdamsvej 3, 2200 Copenhagen, Denmark
2
Department of Clinical Physiology, Nuclear Medicine & PET, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, 2100 Copenhagen, Denmark
*
Author to whom correspondence should be addressed.
Academic Editor: John Dickson
Received: 27 January 2015 / Revised: 5 March 2015 / Accepted: 9 March 2015 / Published: 27 March 2015
(This article belongs to the Collection Feature Papers)
View Full-Text   |   Download PDF [1399 KB, uploaded 27 March 2015]   |  

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 64Cu-ATSM and extract useful physiological parameters. Methods: Tumor-bearing mice underwent 90-min dynamic PET scans with 64Cu-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 64Cu-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). Conclusion: This study shows the feasibility to extract relevant parameters from voxel-wise pharmacokinetic analysis to be used for preclinical validation of 64Cu-ATSM as a hypoxia-specific PET tracer. View Full-Text
Keywords: kinetic modeling; 64Cu-ATSM; hypoxia; cancer; PET; PET/CT; xenograft tumors; voxel-wise pharmacokinetic analysis; parametric mapping kinetic modeling; 64Cu-ATSM; hypoxia; cancer; PET; PET/CT; xenograft tumors; voxel-wise pharmacokinetic analysis; parametric mapping
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Li, F.; Jørgensen, J.T.; Madsen, J.; Kjaer, A. Pharmacokinetic Analysis of 64Cu-ATSM Dynamic PET in Human Xenograft Tumors in Mice. Diagnostics 2015, 5, 96-112.

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