Specific imaging of tumor and metastasis is a major focused initiative sponsored by the NCI for in vivo molecular and cellular imaging. This emphasis acknowledges the positive impact on cancer diagnosis and treatment that can be gleaned from advances in the imaging field and utilizes the differential biology between tumor and normal tissues. The ability of solid tumors to grow and metastasize requires the process of tumor angiogenesis and is linked to the lethality associated with malignant diseases. Tumor blood vessels are distinct from normal tissue vasculatures and can serve to discriminate tumors from normal tissues. Using resources unique to our laboratories, Brown and Modzelewski previously described a family of small peptides that bind specifically to tumor-derived endothelial cells (TDEC) from a murine squamous cell carcinoma model (SCC VII/SF). Through in vitro screening, peptide MW3 exhibited the highest binding specificity to TDEC. Therefore, we propose to develop a magnetic resonance imaging (MRI)-based technology for in vivo tumor imaging utilizing MW3 and its ability to target tumor endothelial cells. MRI is a tool that offers excellent anatomical resolution in diagnostic imaging. Such resolution is particularly important for defining local tumor involvement and in cases of recurrent disease. However, the ability of MRI in discriminating normal from malignant tissue is limited. We propose that active targeting of tumor endothelium, based on targeted delivery of MRI contrast agents (gadolinium [Gd(lll)] chelates), can improve the discriminatory sensitivity and specificity between cancerous and normal tissues. The level of relative tumor enhancement is proportional to the relative concentration of localized chelates within the tumor, which can be amplified by targeted delivery of "polymerized" chelates. By coupling MW3 (with its tumor endothelial targeting ability) to Janus dendrimer (a polymerized Gd(lll) chelate), we propose to develop a technology for enhanced tumor-specific in vivo imaging. [unreadable] [unreadable] [unreadable]
NIH ExPorter
NIH ExPorter