Fluorine-18 2-Fluoro 2-deoxyglucose ( [18] F FDG) positron emission tomography and computed tomography (PET/CT) is a powerful imaging tool for cancer detection and monitoring response to therapy in various malignancies. However, evaluation of response to therapy may be negatively influenced by its non-specificity (uptake in inflammatory/reactive cells). [18] F-labeled dimeric RGD peptide [^?F] FPA-PEG3-E[c(RGDyK)]2 ( [18] F] FPPRGD2), a novel radiopharmaceutical recently developed at Stanford for imaging of tumor integrin expression, may provide more accurate evaluation of response to anti-angiogenesis therapy in subjects with lung cancer. We already successfully performed small animal imaging studies demonstrating the feasibility of [ [18] F] FPPRGD2 PET imaging and the possibility to monitor response to anti-angiogenesis therapy. The first in human (healthy volunteer) administration of [ [18] F] FPPRGD2 followed by PET/CT was already done on June 22, 2009. Magneto-nano protein chips (magnetic chips) enable protein profiling of mouse or human serum samples in a high throughput and multiplexed format, and represent an exciting, powerful tool for exploring many facets of the signaling pathway network in cancer. The vascular endothelial growth factor (VEGF) and human epidermal growth factor receptor (HER-1/EGFR) have been identified as key molecular targets for therapy in non-small-cell lung cancer (NSCLC). Conventional tumor imaging with contrast enhanced CT relies on changes in size to evaluate response to therapy. However, targeted therapies may not cause a significant change in the size of the lesions. Therefore, functional molecular imaging may provide earlier and more accurate means of assessing response to these new drugs. Based on the promising preliminary preclinical results we will attempt to recruit 50 subjects with NSCLC to investigate the hypotheses that [[18] F] FPPRGD2 PET/CT is feasible and that in combination with magnetonano sensors measurements of EGFR pathways can assess and predict the response to targeted Tarceva/Avastin or Vandetanib therapy in NSCLC.
Aim 1 : Evaluate the efficacy and feasibility of f [18] F] FPPRGD2 PET/CT scanning in patients with NSCLC.
Aim 2 : Evaluate the combination of [ [18] F] FPPRGD2 PET/CT and magneto-nano sensors for early assessment and prediction of response to Tarceva/Avastin or Vandetanib therapy in patients with NSCLC.
The introduction of targeted therapy in NSCLC such as Tarceva/Avastin or Zactima warrants the development and validation of novel non-invasive methods to predict and assess response to such treatments, beyond the current imaging methods relying on changes in anatomy. We identified and tested in small animal studies a new PET radiopharmaceutical targeting integrins expression and plan on using It in human subjects with NSCLC In order to predict and evaluate response to anti-angiogenesis drugs. This will be done in combination with another novel approach using magneto-nanosensors to detect changes in proteins indicative of response to EGFR TK inhibitors in NSCLC. This may result in improved patient care and significant reduction in healthcare costs.
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