Dynamic 2-Deoxy-2-[F]Fluoro-D-Glucose Positron Emission Tomography for Chemotherapy Response Monitoring of Breast Cancer Xenografts.

Purpose: Non-invasive response monitoring can potentially be used to guide therapy selection for breast cancer patients. We employed dynamic 2-deoxy-2-[F]fluoro-D-glucose positron emission tomography ([F]FDG PET) to evaluate changes in three breast cancer xenograft lines in mice following three chemotherapy regimens.

Procedures: Sixty-six athymic nude mice bearing bilateral breast cancer xenografts (two basal-like and one luminal-like subtype) underwent three 60 min [F]FDG PET scans. Scans were performed prior to and 3 and 10 days after treatment with doxorubicin, paclitaxel, or carboplatin. Tumor growth was monitored in parallel. A pharmacokinetic compartmental model was fitted to the tumor uptake curves, providing estimates of transfer rates between the vascular, non-metabolized, and metabolized compartments. Early and late standardized uptake values (SUV and SUV, respectively); the rate constants k , k , and k , and the intravascular fraction v were estimated. Changes in tumor volume were used as a response measure. Multivariate partial least-squares regression (PLSR) was used to assess if PET parameters could model tumor response and to identify PET parameters with the largest impact on response.

Results: Treatment responders had significantly larger perfusion-related parameters (k and k ) and lower metabolism-related parameter (k ) than non-responders 10 days after the start of treatment. These findings were further supported by the PLSR analysis, which showed that k and k at day 10 and changes in k explained most of the variability in response to therapy, whereas SUV and particularly SUV were of lesser importance.

Conclusions: Overall, rate parameters related to both tumor perfusion and metabolism were associated with tumor response. Conventional metrics of [F]FDG uptake such as SUV and SUV apparently had little relation to tumor response, thus necessitating full dynamic scanning and pharmacokinetic analysis for optimal evaluation of chemotherapy-induced changes in breast cancers.