There is a vital need for quantitative assessment of cancer therapy response. CT and standard MRI cannot provide information on the molecular, biochemical and physiologic properties of cancer tissues. Therefore, novel quantitative imaging techniques and protocols are needed to reveal biomarkers of molecular events induced by cancer therapy. In particular, early imaging of molecularly targeted pathways predicted to be essential for effective cancer therapy is highly likely to play a key role in patient management in the future. F- 18 FDG-PET can assess the glycolytic response of tumors to chemotherapy and decreases in FDG uptake after the first chemotherapy cycle correlate with better outcome. F-18 FLT PET measures cell proliferation rate, another fundamental process in malignancy. Apoptosis is the primary mechanism of action of most anticancer drugs and can be monitored by the novel PET tracer F-18 ApoSense. In all cancer therapy trials antiangiogenic effect will be measured by DCE MRI in addition to perfusion MRI. Similarly, MRSI can be used to assess choline metabolism, which reflects membrane turnover, through the measurement of total choline and phosphocholine. Finally, triple quantum filtered sodium MRI has been proposed to assess proliferative activity in tumors and changes in cell volume fraction as a result of cell kill. In this project, measures of novel quantitative imaging biomarkers will be combined with patient outcome and tissue biomarkers to develop predictive methodologies for early assessment of response to cancer therapy. The overarching goal of this project will be to standardize PET-CT and MRI protocols, to accurately and reproducibly measure changes in imaging biomarkers during cancer therapy trials, in order to optimize early predictions of subsequent clinical outcomes. Quantitative imaging will be performed in malignant brain tumors with responses to molecularly targeted agents imaged by F-18 ApoSense, F-18 FLT and MRI. Quantitative imaging will also be performed in recurrent or metastatic squamous cell carcinoma of head and neck using novel targeted agents against epidermal growth factor receptor (EGFR) and angiogenesis, including vascular endothelial growth factor (VEGF) and VEGF receptor (VEGFR). The type and timing of imaging are aimed at more specific measurements of the effects on the drug target, to provide the earliest indicator of therapeutic response. Development and use of quantitative imaging for early therapy assessment will greatly facilitate patient management, by sparing patients from weeks or months of toxicity and ineffective treatment.

Public Health Relevance

In this project, measures of novel quantitative imaging biomarkers will be combined with cancer patient outcome to develop predictive methodologies for early assessment of response to cancer therapy. Imaging biomarkers of therapy induced early changes in tumor biology will be serially obtained and rigidly quantified. Development and use of quantitative imaging for early therapy assessment will greatly facilitate cancer patient management by sparing patients from weeks or months of toxicity and ineffective treatment.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01CA140230-05
Application #
8549701
Study Section
Special Emphasis Panel (ZCA1-SRRB-9 (M1))
Program Officer
Nordstrom, Robert J
Project Start
2009-09-01
Project End
2014-07-31
Budget Start
2013-08-01
Budget End
2014-07-31
Support Year
5
Fiscal Year
2013
Total Cost
$104,190
Indirect Cost
$100,994
Name
University of Pittsburgh
Department
Radiation-Diagnostic/Oncology
Type
Schools of Medicine
DUNS #
004514360
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
Nakajima, Erica C; Laymon, Charles; Oborski, Matthew et al. (2014) Quantifying metabolic heterogeneity in head and neck tumors in real time: 2-DG uptake is highest in hypoxic tumor regions. PLoS One 9:e102452
Oborski, Matthew J; Demirci, Emre; Laymon, Charles M et al. (2014) Assessment of early therapy response with 18F-FLT PET in glioblastoma multiforme. Clin Nucl Med 39:e431-2
Bural, Gonca G; Lieberman, Frank; Mountz, James M (2014) Use of 111In-pentetreotide scan in a subject with treatment refractory atypical meningioma. Clin Nucl Med 39:342-5
Mountz, James M; Yankeelov, Thomas E; Rubin, Daniel L et al. (2014) Letter to cancer center directors: Progress in quantitative imaging as a means to predict and/or measure tumor response in cancer therapy trials. J Clin Oncol 32:2115-6
Laymon, Charles M; Bowsher, James E (2013) Anomaly Detection and Artifact Recovery in PET Attenuation-Correction Images Using the Likelihood Function. IEEE J Sel Top Signal Process 7:
Oborski, Matthew J; Laymon, Charles M; Lieberman, Frank S et al. (2013) Distinguishing pseudoprogression from progression in high-grade gliomas: a brief review of current clinical practice and demonstration of the potential value of 18F-FDG PET. Clin Nucl Med 38:381-4
Imani, Farzin; Boada, Fernando E; Lieberman, Frank S et al. (2012) Comparison of proton magnetic resonance spectroscopy with fluorine-18 2-fluoro-deoxyglucose positron emission tomography for assessment of brain tumor progression. J Neuroimaging 22:184-90