FLT-PET/CT as a Biomarker of Therapeutic Response in Pemetrexed Therapy for Non-Small Cell Lung Cancer
Technical Report,30 Sep 2014,29 Sep 2016
University of Pennsylvania Perelman School of Medicine Philadelphia United States
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PemetrexedPEM, a standard therapy for non-squamous non-small cell lung cancer NSCLC, inhibits the de novo thymidine pathway, resulting in a transient burst of metabolism through the salvage pathway, an effect detected as a flare of activity by 18F-thymidine FLT-PET. FLT is a reliable biomarker of proliferation, and post-therapeutic changes in tumor FLT avidity predicts therapeutic response in a range of malignancies. However, FLT as a measure of therapeutic response in NSCLC is not well studied. Our overarching hypothesis is that FLT-PET will allow early assessment of therapeutic response in NSCLC with the following specific aimsSpecific Aim 1 To determine the optimal timing to measure FLT flare, an imaging biomarker of successful PEM-induced TS inhibition in a NSCLC preclinical model. Specific Aim 2 To conduct a proof-of-concept clinical study of FLT flare and FLT-measured changes in tumor proliferation at 2 weeks of therapy as predictors of NSCLC response to PEM. During the research period, we have determined that the optimal time to observe FLT flare in vivo is at 2 hrs following therapy start. This data has been translated to an open clinical trial of FLT-PET as a biomarker of therapy response in NSCLC proposed in Specific Aim 2.
- Medicine and Medical Research