Diagnostic targeting of colon cancer using a novel fluorescent somatostatin conjugate in a mouse xenograft model

Abstract

Colorectal carcinoma is one of the more prevalent, highly malignant human tumors, occurring in about 7% of the population. However, if diagnosed and treated in its early stages, colon cancer is curable. In our study, we used a mouse xenograft model to investigate the capability of a fluorescent conjugate of a novel synthetic somatostatin (SST) analog to improve detection of human colorectal tumors that are characterized by over-expressed SST receptors. Human HT-29 colon carcinomas were induced in nude mice. After administration of the fluorescent SST conjugate, in vivo lowand high-magnification fluorescence microscopy, as well as highresolution spectrally resolved imaging were performed, and the time-dependent biodistribution was determined quantitatively (using fiber-optic spectroscopy). Administration of the conjugate (at concentrations of 6 mg/kg body weight) enabled targeting small (1-5 mm diameter) tumors with high sensitivity and selectivity. Toxicity studies at dosages up to 1,000 mg/kg body weight did not reveal any drug related abnormalities. In conclusion, the SST conjugate significantly enhanced the detection of HT-29 colon tumors by fluorescence imaging because of a 5-to 8-fold increase in the contrast between malignant and normal tissues.

Targeted Optical Imaging Agents in Cancer: Focus on Clinical Applications

“…Peptides have low likelihood to elicit an immune response which allows for repeat use. Peptide analogs with good stability, binding properties, and pharmacokinetic behavior have been used clinically to image neuroendocrine tumors, adenocarcinomas, lymphomas, and melanomas [ 97 – 99 ]. Peptides can be labeled with a variety of fluorophores, including visible and NIR dyes.…”

Fluorescent Dye Conjugates for Optical Imaging of Cancer

“…Recently, another fluorescent conjugate of a synthetic somatostatin analog was also reported for tumor targeting and imaging using various optical techniques. 91 …”

Peptide-Based Probes for Targeted Molecular Imaging

“…ITCC-octreotate displayed fast and thorough receptor binding properties in SSTr-2 overexpressing RIN38/SSTr-2 cells and provided three-fold higher tumor fluorescence in mice bearing RIN38/SSTr-2 tumors from 3–24 h after intravenous injection. Different libraries of SST analogs were also labeled with fluorophores and tested in SSTr-positive NCI-H69 human SCLC tumors and HT-29 colon tumor bearing mice, respectively (90, 91). For GRPr imaging, Alexa Fluor 680-[Gly-Gly-Gly]-Bombesin(7–14) was synthesized and demonstrated specific GRPr targeting ability in vitro and in mice bearing T-47D breast cancer cells (92).…”