New strategy for monitoring targeted therapy: molecular imaging

Abstract

Targeted therapy is becoming an increasingly important component in the treatment of cancer. How to accurately monitor targeted therapy has been crucial in clinical practice. The traditional approach to monitor treatment through imaging has relied on assessing the change of tumor size by refined World Health Organization criteria, or more recently, by the Response Evaluation Criteria in Solid Tumors. However, these criteria, which are based on the change of tumor size, show some limitations for evaluating targeted therapy. Currently, genetic alterations are identified with prognostic as well as predictive potential concerning the use of molecularly targeted drugs. Conversely, considering the limitations of invasiveness and the issue of expression heterogeneity, molecular imaging is better able to assay in vivo biologic processes noninvasively and quantitatively, and has been a particularly attractive tool for monitoring treatment in clinical cancer practice. This review focuses on the applications of different kinds of molecular imaging including positron emission tomography-, magnetic resonance imaging-, ultrasonography-, and computed tomography-based imaging strategies on monitoring targeted therapy. In addition, the key challenges of molecular imaging are addressed to successfully translate these promising techniques in the future.

Quantitative Imaging in Cancer Clinical Trials

“…Quantitative imaging with volumetric CT (2) or PET imaging (7) has the potential to provide early assessment of molecularly targeted therapies by assessing biological changes in tumors that are likely to be clinically relevant even in the absence of tumor shrinkage. For example, in non-small cell lung cancer patients treated with erlotinib, a small-molecule tyrosine kinase inhibitor (TKI) of the epidermal growth factor receptor (EGFR) a partial metabolic response, as measured by 2-[(18)F]-fluoro-2-deoxy-D-glucose PET (FDG-PET), is associated with improved progression free and overall survival, even in the absence of RECIST response, either during or after therapy (8).…”

Quantitative multimodality imaging in cancer research and therapy

“…Importantly, changes in tumour size might underestimate or fail to capture the antitumour efficacy of newer drugs that might be predominantly cytostatic, rather than cytotoxic, such as antiangiogenic agents. 48–50 However, the fact that the RECIST criteria can adequately capture when a therapeutic regimen is failing should be recognized; in such cases the size of the tumour will frequently increase early in the course of therapy. The promise of multimodality functional imaging in the context of treatment-response assessments lies in the presumed ability of this approach to enable characterization of the underlying physiological, cellular, and molecular changes with greater sensitivity and predictive ability than changes in anatomical size.…”

18F–FDG-PET/CT and diffusion-weighted MRI for monitoring a BRAF and CDK 4/6 inhibitor combination therapy in a murine model of human melanoma

“…However, in contrast to traditional, primarily cytotoxic therapies, novel targeted therapies exhibit only subtle effects on tumor size [ 13 ]. Thus, morphology-based tumor response criteria are of only limited applicability in targeted therapy regimens [ 14 ]. Functional and molecular imaging modalities allow for a non-invasive tumor characterization beyond morphology, delivering information on tumor pathophysiology such as tumor glucose metabolism ( 18 F–fluorodeoxyglucose positron emission tomography; 18 F–FDG-PET) and tumor cellularity (diffusion-weighted MRI; DW-MRI).…”