Kinetic analysis of 2-[11C]thymidine PET imaging studies of malignant brain tumors: compartmental model investigation and mathematical analysis.
2-[11C]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 estirmine whether it can distinguish between thymidine transport and retention.


RESULTS
Sensitivity and identifiability analysis suggested that the non-CO2 metabolite parameters could be fixed without significantly affecting thymidine parameter estimation. Simulations showed that K1t and KTdR 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.


CONCLUSIONS
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.
Wells
Joanne M
JM
University of Washington, USA.
Mankoff
David A
DA
Muzi
Mark
M
O'Sullivan
Finbarr
F
Eary
Janet F
JF
Spence
Alexander M
AM
Krohn
Kenneth A
KA
D001693:Biological Transport, Active; D001932:Brain Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology; D002250:Carbon Radioisotopes; D002455:Cell Division; D004273:DNA, Neoplasm / Q000096:biosynthesis; D006801:Humans; D008433:Mathematics; D008959:Models, Neurological; D013936:Thymidine / Q000378:metabolism; D014055:Tomography, Emission-Computed
D002250:Carbon Radioisotopes; D004273:DNA, Neoplasm; D013936:Thymidine