Pharmacokinetic Analysis of 64Cu-ATSM Dynamic PET in Human Xenograft Tumors in Mice
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...
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| Format: | Article |
| Language: | English |
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MDPI AG
2015-03-01
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| Series: | Diagnostics |
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| Online Access: | http://www.mdpi.com/2075-4418/5/2/96 |
| _version_ | 1828153824175456256 |
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| author | Fan Li Jesper Tranekjær Jørgensen Jacob Madsen Andreas Kjaer |
| author_facet | Fan Li Jesper Tranekjær Jørgensen Jacob Madsen Andreas Kjaer |
| author_sort | Fan Li |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-11T22:31:32Z |
| format | Article |
| id | doaj.art-dcd2b2ce04844d3a98ec5d8aca7b1119 |
| institution | Directory Open Access Journal |
| issn | 2075-4418 |
| language | English |
| last_indexed | 2024-04-11T22:31:32Z |
| publishDate | 2015-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Diagnostics |
| spelling | doaj.art-dcd2b2ce04844d3a98ec5d8aca7b11192022-12-22T03:59:24ZengMDPI AGDiagnostics2075-44182015-03-01529611210.3390/diagnostics5020096diagnostics5020096Pharmacokinetic Analysis of 64Cu-ATSM Dynamic PET in Human Xenograft Tumors in MiceFan Li0Jesper Tranekjær Jørgensen1Jacob Madsen2Andreas Kjaer3Cluster for Molecular Imaging, Faculty of Health Sciences, University of Copenhagen, Blegdamsvej 3, 2200 Copenhagen, DenmarkCluster for Molecular Imaging, Faculty of Health Sciences, University of Copenhagen, Blegdamsvej 3, 2200 Copenhagen, DenmarkDepartment of Clinical Physiology, Nuclear Medicine & PET, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, 2100 Copenhagen, DenmarkCluster for Molecular Imaging, Faculty of Health Sciences, University of Copenhagen, Blegdamsvej 3, 2200 Copenhagen, DenmarkThe 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.http://www.mdpi.com/2075-4418/5/2/96kinetic modeling64Cu-ATSMhypoxiacancerPETPET/CTxenograft tumorsvoxel-wise pharmacokinetic analysisparametric mapping |
| spellingShingle | Fan Li Jesper Tranekjær Jørgensen Jacob Madsen Andreas Kjaer Pharmacokinetic Analysis of 64Cu-ATSM Dynamic PET in Human Xenograft Tumors in Mice Diagnostics kinetic modeling 64Cu-ATSM hypoxia cancer PET PET/CT xenograft tumors voxel-wise pharmacokinetic analysis parametric mapping |
| title | Pharmacokinetic Analysis of 64Cu-ATSM Dynamic PET in Human Xenograft Tumors in Mice |
| title_full | Pharmacokinetic Analysis of 64Cu-ATSM Dynamic PET in Human Xenograft Tumors in Mice |
| title_fullStr | Pharmacokinetic Analysis of 64Cu-ATSM Dynamic PET in Human Xenograft Tumors in Mice |
| title_full_unstemmed | Pharmacokinetic Analysis of 64Cu-ATSM Dynamic PET in Human Xenograft Tumors in Mice |
| title_short | Pharmacokinetic Analysis of 64Cu-ATSM Dynamic PET in Human Xenograft Tumors in Mice |
| title_sort | pharmacokinetic analysis of 64cu atsm dynamic pet in human xenograft tumors in mice |
| topic | kinetic modeling 64Cu-ATSM hypoxia cancer PET PET/CT xenograft tumors voxel-wise pharmacokinetic analysis parametric mapping |
| url | http://www.mdpi.com/2075-4418/5/2/96 |
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