Research Project
7962885
Lung cancer causes nearly one million deaths annually. With current imaging methods (Chest x-ray, CT), the main limitations for accurate, early detection (which could improve survival) continue to be lack of specificity for malignancies (up to 98% "false positives") and the inability to correctly classify nodules <7mm in diameter as cancer. Thus, there is a crucial need for a new technology to improve specificity and sensitivity of detection. Our anti-transferrin receptor scFv immunoliposome (scL) is a systemically administered, tumor-targeting nanocomplex (-100nm) for delivery of molecular medicines. It efficiently and specifically delivers various payloads to tumor cells in vivo, and is in Phase I clinical trials for p53 gene therapy. We developed a tumor-targeting scL-MR Imaging complex which encapsulates gadopentetate-dimeglumine (gad-d). New capabilities resulted from delivery of gad-d directly and preferentially into tumor cells. scL-gad-d demonstrated enhanced tumor image intensity compared to free gad-d. Moreover, scL-gad-d (not free gad-d) enhanced and identified lung tumors as small as 1-4 pixels (O.1-0.4mm), a size at least 5X smaller than possible with current technology. In this Phase I proposal we will develop a lyophilized, stable form of scL-gad-d for use in the clinic, the next step in moving towards an IND application. Numerous false positives found by current imaging methods limit early detection of lung cancer. Tumor[unreadable] specific nanocomplex delivery of MRI agent gad-d has high affinity for cancer cells resulting in improved sensitivity/specificity in detecting small lung cancers. Its use will provide improvement in early detection of primary lung cancer and metastases with a major impact on cancer detection, diagnosis and treatment.
