Kinetic analysis of 2-[11C]thymidine PET imaging studies of malignant brain tumors: Compartmental model investigation and mathematical analysis

Joanne M. Wells, David A. Mankoff, Mark Muzi, Finbarr O'Sullivan, Janet F. Eary, Alexander M. Spence, Kenneth A. Krohn

Research output: Contribution to journalArticle

26 Scopus citations

Abstract

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 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-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. 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.

Original languageEnglish (US)
Pages (from-to)151-159
Number of pages9
JournalMolecular Imaging
Volume1
Issue number3
DOIs
StatePublished - Jul 2002

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Keywords

  • Brain tumors
  • Kinetic modeling
  • PET
  • Proliferation
  • []Thymidine

ASJC Scopus subject areas

  • Biotechnology
  • Molecular Medicine
  • Biomedical Engineering
  • Radiology Nuclear Medicine and imaging
  • Condensed Matter Physics

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