This project will develop targeted nano-probes for molecular imaging to enable non-invasive early detection of incipient cancer, affording substantive improvements in sensitivity and selectivity. It brings together three research groups with complementary expertise in angiogenesis and mouse models of cancer (Hanahan, UCSF), in vascular profiling (Ruoslahti, Burnham Institute), and in clinical and experimental molecular imaging (Franc, UCSF). Peptides have been discovered that specifically home through the circulatory system to the angiogenic blood or lymphatic neo-vasculature of high-grade neoplasias and/or invasive carcinomas. These vascular signatures can distinguish cancerous lesions from their cognate normal tissue, as well as from blood/lymphatic vessels in other organs and neoplastic conditions.
The aims are: 1. Develop imaging nanoprobes for detecting the blood and lymphatic neo-vasculature in two mouse models of cancer that undergo stepwise progression to carcinoma, using validated signature-finding peptides as modular specificity elements linked to agents appropriate for imaging with SPECT, PET, or MRI. 2. Discover and characterize a repertoire of new signature-finding peptides for blood and lymphatic vasculature of cervical and pancreatic ductal neoplasias and cancer, and determine which identify analogous lesions in the cognate human diseases. 3. Competitively evaluate mouse/human signature-finding peptides (and mixtures thereof) from Aim 2 to identify the best at delivering imaging reporters to the aberrant blood and lymphatic vasculatures in the mouse models of cervical (as a prototype) and pancreatic ductal cancer (for its an unmet clinical need). 4. In partnership with Centers of Excellence in Cancer Nanotechnology, test nano-probes in the mouse models consisting of the best human/mouse signature-finding peptides linked to new imaging nanostructures being developed by those centers, to identify optimal candidate nanoprobes for clinical evaluation. The modular imaging nanoprobes to be developed, by delivering imaging agents to organ sites of tumor angiogenesis and lymphangiogenesis, hold promise to enable early detection of human cancer.
| Sugahara, Kazuki N; Teesalu, Tambet; Karmali, Priya Prakash et al. (2010) Coadministration of a tumor-penetrating peptide enhances the efficacy of cancer drugs. Science 328:1031-5 |
| Christine, C W; Starr, P A; Larson, P S et al. (2009) Safety and tolerability of putaminal AADC gene therapy for Parkinson disease. Neurology 73:1662-9 |
| Teesalu, Tambet; Sugahara, Kazuki N; Kotamraju, Venkata Ramana et al. (2009) C-end rule peptides mediate neuropilin-1-dependent cell, vascular, and tissue penetration. Proc Natl Acad Sci U S A 106:16157-62 |
| Sugahara, Kazuki N; Teesalu, Tambet; Karmali, Priya Prakash et al. (2009) Tissue-penetrating delivery of compounds and nanoparticles into tumors. Cancer Cell 16:510-20 |
