Diagnostic targeting of colon cancer using a novel fluorescent somatostatin conjugate in a mouse xenograft model.
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.
Kostenich
Genady
G
Advanced Technology Center, Sheba Medical Center, Tel Hashomer, Israel. genakos@sheba.health.gov.il
Oron-Herman
Mor
M
Kimel
Sol
S
Livnah
Nurit
N
Tsarfaty
Ilan
I
Orenstein
Arie
A
D000818:Animals; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000175:diagnosis* / Q000378:metabolism; D005260:Female; D005453:Fluorescence; D015972:Gene Expression Regulation, Neoplastic; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D009374:Neoplasms, Experimental / Q000175:diagnosis; D017481:Receptors, Somatostatin / Q000378:metabolism*; D013004:Somatostatin / Q000493:pharmacokinetics; D013050:Spectrometry, Fluorescence; D014018:Tissue Distribution; D014183:Transplantation, Heterologous; D015854:Up-Regulation
D017481:Receptors, Somatostatin; D013004:Somatostatin