The primary goal of this Biomedical Research Grant is to translate imaging agents for intraoperative cancer detection and image-guided surgery. Half of all cancer patients undergo surgery to remove their tumor. The single most important predictor of patient survival is a complete surgical resection of the primary tumor, draining lymph nodes, and metastatic lesions. However, up to 40% of surgical patients leave the operating room with malignant cells remaining after resection. Thus, there are urgent unmet needs to develop new and innovative technologies that can assist the surgeon in ensuring complete tumor resection by delineating tumor margins, and identifying micrometastases and draining lymph nodes. We propose a new technology to image patients at the conclusion of the standard-of-care cancer operation in order to discover residual local disease before completing the surgery. While the proposed technologies are broadly applicable to solid tumors, this project is specifically committed to improving detection of lung adenocarcinomas, one of the most aggressive human malignancies. To accomplish this goal, we have assembled a collaborative team at University of Pennsylvania and Purdue University with synergistic expertise in clinical trials, folate biology, chemistry, lung pathology, thoracic surgery and veterinary medicine. The proposed work will optimize three distinct types of contrast agents for a translational intraoperative imaging clinical trial. The first contrast agent uses folate to target a conjugated NIR dye specifically to malignant tissue. The folate-NIR agent will be evaluated in a first-in- human clinical trial of lung adenocarcinoma patients in order to determine if there is a benefit of intraoperative imaging to standard-of-care surgical approaches. The second contrast agent uses the same targeting approach to deliver a near-infrared dye for EGFR and CCK2R to cancer cells and allow better imaging of diseased cells more deeply buried in the tissues. This will allow for precise tumor localization and more accurate resection of cancers without violating the tumor capsule or seeding the body cavity.

Public Health Relevance

This grant application develops new and innovative technologies for applications in cancer surgery. The main goal is to aid the surgeon in delineating tumor margins, identifying diseased lymph nodes and micrometastases and determining if the tumor has been completely resected. A cocktail of innovative targeted optical contrast agents for lung adenocarcinomas is expected to generate a major impact (80,000 patients/year) in reducing the local and regional recurrence rates of lung cancer after surgery.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA193556-04
Application #
9645544
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Redmond, George O
Project Start
2016-03-01
Project End
2021-02-28
Budget Start
2019-03-01
Budget End
2020-02-29
Support Year
4
Fiscal Year
2019
Total Cost
Indirect Cost
Name
University of Pennsylvania
Department
Surgery
Type
Schools of Medicine
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
Newton, Andrew D; Predina, Jarrod D; Frenzel-Sulyok, Lydia G et al. (2018) Intraoperative near-infrared imaging can identify sub-centimeter colorectal cancer lung metastases during pulmonary metastasectomy. J Thorac Dis 10:E544-E548
Predina, Jarrod D; Newton, Andrew D; Connolly, Courtney et al. (2018) Identification of a Folate Receptor-Targeted Near-Infrared Molecular Contrast Agent to Localize Pulmonary Adenocarcinomas. Mol Ther 26:390-403
Predina, Jarrod D; Newton, Andrew D; Xia, Leilei et al. (2018) An open label trial of folate receptor-targeted intraoperative molecular imaging to localize pulmonary squamous cell carcinomas. Oncotarget 9:13517-13529
Predina, Jarrod D; Okusanya, Olugbenga; D Newton, Andrew et al. (2018) Standardization and Optimization of Intraoperative Molecular Imaging for Identifying Primary Pulmonary Adenocarcinomas. Mol Imaging Biol 20:131-138
Newton, Andrew D; Predina, Jarrod D; Corbett, Christopher J et al. (2018) Optimization of Second Window Indocyanine Green for Intraoperative Near-Infrared Imaging of Thoracic Malignancy. J Am Coll Surg :
Predina, Jarrod D; Newton, Andrew; Corbett, Christopher et al. (2018) Localization of Pulmonary Ground-Glass Opacities with Folate Receptor-Targeted Intraoperative Molecular Imaging. J Thorac Oncol 13:1028-1036
Predina, Jarrod D; Newton, Andrew; Deshpande, Charuhas et al. (2018) Utilization of targeted near-infrared molecular imaging to improve pulmonary metastasectomy of osteosarcomas. J Biomed Opt 23:1-4
Newton, Andrew D; Predina, Jarrod D; Nie, Shuming et al. (2018) Intraoperative fluorescence imaging in thoracic surgery. J Surg Oncol 118:344-355
Predina, Jarrod D; Newton, Andrew; Kennedy, Greg et al. (2017) Near-Infrared Intraoperative Imaging Can Successfully Identify Malignant Pleural Mesothelioma After Neoadjuvant Chemotherapy. Mol Imaging 16:1536012117723785
Eruslanov, Evgeniy B; Singhal, Sunil; Albelda, Steven M (2017) Mouse versus Human Neutrophils in Cancer: A Major Knowledge Gap. Trends Cancer 3:149-160

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