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? 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.
