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

Genady Kostenich*, Mor Oron-Herman, Sol Kimel, Nurit Livnah, Ilan Tsarfaty, Arie Orenstein

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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 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.

Original languageEnglish
Pages (from-to)2044-2049
Number of pages6
JournalInternational Journal of Cancer
Volume122
Issue number9
DOIs
StatePublished - 1 May 2008

Keywords

  • Fluorescent somatostatin conjugate
  • HT-29 colon carcinoma
  • Mouse xenograft
  • Selective uptake
  • Specific targeting
  • Spectrally resolved imaging

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