Kinetic Analysis of 2-[C]Thymidine PET Imaging Studies of Malignant Brain Tumors: Compartmental Model Investigation and Mathematical Analysis
2-[ 11 C]Thymidine (TdR), a PET tracer for cellular proliferation, may be advantageous for monitoring brain tumor progression and response to therapy. We previously described and validated a five-compartment model for thymidine incorporation into DNA in somatic tissues, but the effect of the blood–b...
Saved in:
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
SAGE Publishing
2002-07-01
|
| Series: | Molecular Imaging |
| Online Access: | https://doi.org/10.1162/15353500200202112 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1846097841575952384 |
|---|---|
| author | Joanne M. Wells David A. Mankoff Mark Muzi Finbarr O'Sullivan Janet F. Eary Alexander M. Spence Kenneth A. Krohn |
| author_facet | Joanne M. Wells David A. Mankoff Mark Muzi Finbarr O'Sullivan Janet F. Eary Alexander M. Spence Kenneth A. Krohn |
| author_sort | Joanne M. Wells |
| collection | DOAJ |
| description | 2-[ 11 C]Thymidine (TdR), a PET tracer for cellular proliferation, may be advantageous for monitoring brain tumor progression and response to therapy. We previously described and validated a five-compartment model for thymidine incorporation into DNA in somatic tissues, but the effect of the blood–brain barrier on the transport of TdR and its metabolites necessitated further validation before it could be applied to brain tumors. Methods: We investigated the behavior of the model under conditions experienced in the normal brain and brain tumors, performed sensitivity and identifiability analysis to determine the ability of the model to estimate the model parameters, and conducted simulations to determine whether it can distinguish between thymidine transport and retention. Results: Sensitivity and identifiability analysis suggested that the non-CO 2 metabolite parameters could be fixed without significantly affecting thymidine parameter estimation. Simulations showed that K 1t and K TdR could be estimated accurately ( r = .97 and .98 for estimated vs. true parameters) with standard errors < 15%. The model was able to separate increased transport from increased retention associated with tumor proliferation. Conclusion: Our model adequately describes normal brain and brain tumor kinetics for thymidine and its metabolites, and it can provide an estimate of the rate of cellular proliferation in brain tumors. |
| format | Article |
| id | doaj-art-9c53b62f8b0a441aa6d7ed165d7d2f5f |
| institution | Kabale University |
| issn | 1536-0121 |
| language | English |
| publishDate | 2002-07-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Molecular Imaging |
| spelling | doaj-art-9c53b62f8b0a441aa6d7ed165d7d2f5f2025-01-02T02:59:15ZengSAGE PublishingMolecular Imaging1536-01212002-07-01110.1162/1535350020020211210.1162_15353500200202112Kinetic Analysis of 2-[C]Thymidine PET Imaging Studies of Malignant Brain Tumors: Compartmental Model Investigation and Mathematical AnalysisJoanne M. Wells0David A. MankoffMark Muzi1Finbarr O'Sullivan2Janet F. Eary3Alexander M. Spence4Kenneth A. Krohn5University of WashingtonUniversity of WashingtonUniversity College CorkUniversity of WashingtonUniversity of WashingtonUniversity of Washington2-[ 11 C]Thymidine (TdR), a PET tracer for cellular proliferation, may be advantageous for monitoring brain tumor progression and response to therapy. We previously described and validated a five-compartment model for thymidine incorporation into DNA in somatic tissues, but the effect of the blood–brain barrier on the transport of TdR and its metabolites necessitated further validation before it could be applied to brain tumors. Methods: We investigated the behavior of the model under conditions experienced in the normal brain and brain tumors, performed sensitivity and identifiability analysis to determine the ability of the model to estimate the model parameters, and conducted simulations to determine whether it can distinguish between thymidine transport and retention. Results: Sensitivity and identifiability analysis suggested that the non-CO 2 metabolite parameters could be fixed without significantly affecting thymidine parameter estimation. Simulations showed that K 1t and K TdR could be estimated accurately ( r = .97 and .98 for estimated vs. true parameters) with standard errors < 15%. The model was able to separate increased transport from increased retention associated with tumor proliferation. Conclusion: Our model adequately describes normal brain and brain tumor kinetics for thymidine and its metabolites, and it can provide an estimate of the rate of cellular proliferation in brain tumors.https://doi.org/10.1162/15353500200202112 |
| spellingShingle | Joanne M. Wells David A. Mankoff Mark Muzi Finbarr O'Sullivan Janet F. Eary Alexander M. Spence Kenneth A. Krohn Kinetic Analysis of 2-[C]Thymidine PET Imaging Studies of Malignant Brain Tumors: Compartmental Model Investigation and Mathematical Analysis Molecular Imaging |
| title | Kinetic Analysis of 2-[C]Thymidine PET Imaging Studies of Malignant Brain Tumors: Compartmental Model Investigation and Mathematical Analysis |
| title_full | Kinetic Analysis of 2-[C]Thymidine PET Imaging Studies of Malignant Brain Tumors: Compartmental Model Investigation and Mathematical Analysis |
| title_fullStr | Kinetic Analysis of 2-[C]Thymidine PET Imaging Studies of Malignant Brain Tumors: Compartmental Model Investigation and Mathematical Analysis |
| title_full_unstemmed | Kinetic Analysis of 2-[C]Thymidine PET Imaging Studies of Malignant Brain Tumors: Compartmental Model Investigation and Mathematical Analysis |
| title_short | Kinetic Analysis of 2-[C]Thymidine PET Imaging Studies of Malignant Brain Tumors: Compartmental Model Investigation and Mathematical Analysis |
| title_sort | kinetic analysis of 2 c thymidine pet imaging studies of malignant brain tumors compartmental model investigation and mathematical analysis |
| url | https://doi.org/10.1162/15353500200202112 |
| work_keys_str_mv | AT joannemwells kineticanalysisof2cthymidinepetimagingstudiesofmalignantbraintumorscompartmentalmodelinvestigationandmathematicalanalysis AT davidamankoff kineticanalysisof2cthymidinepetimagingstudiesofmalignantbraintumorscompartmentalmodelinvestigationandmathematicalanalysis AT markmuzi kineticanalysisof2cthymidinepetimagingstudiesofmalignantbraintumorscompartmentalmodelinvestigationandmathematicalanalysis AT finbarrosullivan kineticanalysisof2cthymidinepetimagingstudiesofmalignantbraintumorscompartmentalmodelinvestigationandmathematicalanalysis AT janetfeary kineticanalysisof2cthymidinepetimagingstudiesofmalignantbraintumorscompartmentalmodelinvestigationandmathematicalanalysis AT alexandermspence kineticanalysisof2cthymidinepetimagingstudiesofmalignantbraintumorscompartmentalmodelinvestigationandmathematicalanalysis AT kennethakrohn kineticanalysisof2cthymidinepetimagingstudiesofmalignantbraintumorscompartmentalmodelinvestigationandmathematicalanalysis |