Positron emission tomography (PET) has seen a dramatic and continued growth in preclinical and clinical research, pharmaceutical applications and molecular imaging diagnostics over the last 20 years. With the recognition that patient outcomes and healthcare costs can be dramatically impacted by the personalization of medicine, there is an obvious need for novel PET molecular imaging agents that measure clinically relevant targets that are surrogates or predictors of disease. A significant and rapidly growing body of literature identifies the integrin subtype ?v?6 as an important target for both molecular imaging and therapy. The ?v?6 integrin is an epithelial-specific cell surface receptor that is undetectable in healthy adult epithelium but is significantly up-regulated in a wide range of epithelial derived cancers including colon, non- small cell lung cancer, ovarian, pancreas, breast, prostate, and oral squamous cell carcinoma. This receptor is often localized to the invasive front and infiltrating edges of tumors and plays a key role in invasion and subsequent metastasis. Currently no ?v?6-directed molecular imaging agent has entered the clinic. We have developed an ?v?6-directed molecular imaging agent, 18F-?v?6-binding-peptide (PEG28- [A20FMDV2(K16R)]-PEG28, 18F-?v?6-BP), a peptide that has high affinity (nM) and selectivity for the integrin ?v?6 and demonstrated favorable pharmacokinetics in tumor-bearing mice and non-human-primates (NHP). We propose to evaluate the safety, biodistribution and dosimetry properties of this ?v?6-directed molecular imaging agent through a first-in-human study in 3 healthy subjects and in 27 patients with cancerous tumors. The biodistribution of the 18F-?v?6-BP will be evaluated by non-invasive blood and whole body PET/CT-based assays, at multiple time points and organ tissue absorbed doses will be calculated. We will generate first?in- human data on biodistribution, metabolism and radiation dosimetry and thus justify further clinical development. The clinical impact of this first-in-human study is immediate for a broad spectrum of diseases and holds potential to break through barriers in the treatment of some of the most lethal malignancies facing clinicians today. ?v?6-directed imaging will provide critical stage and grade (indolence/aggressiveness) information, guide therapy decisions that are difficult to make on the current diagnostic approaches and have a significant outcome for both the under- and over-treated cancer patients. This approach facilitates personalized medicine, with ?v?6-directed imaging allowing for the early detection and response to therapy enabling prediction of outcome and optimized treatment regimes.

Public Health Relevance

Tools to diagnose a wide range of cancers, especially the most aggressive ones, could greatly improve patient outcomes. With the identification of ?v?6, a molecule that is on many cancers and is also linked to a poor survival rate for patients, and our promising lead peptide we now have the opportunity to develop such tools. We therefore propose to perform the first studies in humans to assess our lead peptide.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Research Project (R01)
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Special Emphasis Panel (ZRG1)
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Zhang, Yantian
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University of California Davis
Internal Medicine/Medicine
Schools of Medicine
United States
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