Lung cancer causes nearly one million deaths/year. With current imaging methods (Chest x-ray, CT), the main limitations for accurate, early detection (which could improve survival) are 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, ans is in Phase I clinical trials for p53 gene therapy. We developed a tumor-targeting scL-MR imaging complex encapsulating gadopentetate-dimeglumine (gad-d) that delivered 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 (0.1-0.4mm), a size at least 5x smaller than possible with current technology. In this Phase II proposal we extend our studies to a mouse model of primary lung cancer, further characterize scL-gad-d and perform the studies required for filing and IND on this complex as we move towards clinical trials. 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.
