Longitudinally quantitative FDG-microPET imaging for efficacy of new anticancer drugs: A case study with bortezomib in prostate cancer murine model

Abstract

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Objectives: The quantitative metabolic response of tumors to a treatment measured longitudinally provides a robust tool for pre-clinical evaluation of new anticancer agents and a translational platform for the design of clinical trials.

Methods: The utility of small animal position emission tomography (microPET) coupled with 2'-deoxy-2'-[18F]fluoroglucose (FDG) was investigated for adoption in drug discovery research. Quantitative indices of tumor FDG uptake were developed with an efficacious regimen of bortezomib in a murine model of prostate cancer. SCID mice with CWR22 xenografts were iv-treated with bortezomib at 0.8 mg/kg on days 0, 3, 7, 10 and 14 and imaged with FDG-microPET before, during and after treatment.

Results: Compared to the overwhelming tumor growth in the mice receiving placebo, a 55% tumor growth inhibition was obtained from bortezomib therapy. In addition, more microregions of necrosis were found in the treated tumors. FDG-microPET images successfully revealed the gradual reduction of tumor FDG uptake on day 4 onwards post treatment despite no absolute tumor shrinkage. At the end of the study, the standardized uptake values of FDG in tumors was reduced to 43% of the baseline values. Using the total tumor FDG uptake as a representative of the viable tumor burden, the tumor inhibition by the therapy was 86% at the end of the study.

Conclusions: FDG-microPET imaging can annotate an additional dimension of the efficacy of an anticancer therapy that may otherwise be underestimated by tumor volume measurement, and they reconfirmed the therapeutic benefits of bortezomib in this murine model.