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

• Published in: International journal of cancer 2008-05, Vol.122 (9), p.2044-2049
• Main Authors: Kostenich, Genady, Oron‐Herman, Mor, Kimel, Sol, Livnah, Nurit, Tsarfaty, Ilan, Orenstein, Arie
• Format: Article
• Language: English
• Subjects: Animal tumors. Experimental tumors; Animals; Biological and medical sciences; Cell Line, Tumor; Colonic Neoplasms - diagnosis; Colonic Neoplasms - metabolism; Experimental digestive system and abdominal tumors; Female; Fluorescence; fluorescent somatostatin conjugate; Gene Expression Regulation, Neoplastic; HT‐29 colon carcinoma; Medical sciences; Mice; Mice, Inbred BALB C; Mice, Nude; Microscopy, Confocal; Microscopy, Fluorescence; mouse xenograft; Neoplasms, Experimental - diagnosis; Receptors, Somatostatin - metabolism; selective uptake; Somatostatin - pharmacokinetics; specific targeting; spectrally resolved imaging; Spectrometry, Fluorescence; Tissue Distribution; Transplantation, Heterologous; Tumors; Up-Regulation
• ISSN: 0020-7136; 1097-0215
• DOI: 10.1002/ijc.23353

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 low‐ and high‐magnification fluorescence microscopy, as well as high‐resolution 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. © 2008 Wiley‐Liss, Inc.