A targeted molecular probe for colorectal cancer imaging

T. Attramadal; R. Bjerke; B. Indrevoll; S. Moestue; A. Rogstad; R. Bendiksen; A. Healey; E. Johannesen

doi:10.1117/12.763297

22 February 2008 A targeted molecular probe for colorectal cancer imaging

T. Attramadal, R. Bjerke, B. Indrevoll, S. Moestue, A. Rogstad, R. Bendiksen, A. Healey, E. Johannesen

Proceedings Volume 6867, Molecular Probes for Biomedical Applications II; 686709 (2008) https://doi.org/10.1117/12.763297
Event: SPIE BiOS, 2008, San Jose, California, United States

Abstract

Colorectal cancer is a major cause of cancer death. Morbidity, mortality and healthcare costs can be reduced if the disease can be detected at an early stage. Screening is a viable approach as there is a clear link to risk factors such as age. We have developed a fluorescent contrast agent for use during colonoscopy. The agent is administered intravenously and is targeted to an early stage molecular marker for colorectal cancer. The agent consists of a targeting section comprising a peptide, and a fluorescent reporter molecule. Clinical imaging of the agent is to be performed with a far red fluorescence imaging channel (635 nm excitation/660-700 nm emission) as an adjunct to white light colonoscopy. Preclinical proof of mechanism results are presented. The compound has a K_d of ~3nM. Two human xenograft tumour models were used. Tumour cells were implanted and grown subcutaneously in nude mice. Imaging using a fluorescence reflectance imaging system and quantitative biodistribution studies were performed. Substances tested include the targeted agent, and a scrambled sequence of the peptide (no binding) used as a negative control. Competition studies were also performed by co-administration of 180 times excess unlabelled peptide. Positive imaging contrast was shown in the tumours, with a clear relationship to expression levels (confirmed with quantitative biodistribution data). There was a significant difference between the positive and negative control substances, and a significant reduction in contrast in the competition experiment.

Citation Download Citation

T. Attramadal, R. Bjerke, B. Indrevoll, S. Moestue, A. Rogstad, R. Bendiksen, A. Healey, and E. Johannesen "A targeted molecular probe for colorectal cancer imaging", Proc. SPIE 6867, Molecular Probes for Biomedical Applications II, 686709 (22 February 2008); https://doi.org/10.1117/12.763297

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