Mr. Ragnar Bendiksen Profile

Ragnar Bendiksen

at Cytiva

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Publications (3)

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Proceedings Article | 22 February 2008 Paper

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, 686709 (2008) https://doi.org/10.1117/12.763297

KEYWORDS: Luminescence, Plasma, Colorectal cancer, Blood, Kidney, Liver, Polarization, Tissues, Imaging systems, In vivo imaging

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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.

Proceedings Article | 22 February 2008 Paper

Imaging efficacy of a targeted imaging agent for fluorescence endoscopy

A. Healey, R. Bendiksen, T. Attramadal, R. Bjerke, S. Waagene, A. M. Hvoslef, E. Johannesen

Proceedings Volume 6867, 68670A (2008) https://doi.org/10.1117/12.763345

KEYWORDS: Luminescence, Imaging systems, Colon, Colorectal cancer, Kidney, Laparoscopy, Visualization, Endoscopes, Animal model studies, Tissues

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Colorectal cancer is a major cause of cancer death. A significant unmet clinical need exists in the area of screening for earlier and more accurate diagnosis and treatment. We have identified a fluorescence imaging agent targeted to an early stage molecular marker for colorectal cancer. The agent is administered intravenously and imaged in a far red imaging channel as an adjunct to white light endoscopy. There is experimental evidence of preclinical proof of mechanism for the agent. In order to assess potential clinical efficacy, imaging was performed with a prototype fluorescence endoscope system designed to produce clinically relevant images. A clinical laparoscope system was modified for fluorescence imaging. The system was optimised for sensitivity. Images were recorded at settings matching those expected with a clinical endoscope implementation (at video frame rate operation). The animal model was comprised of a HCT-15 xenograft tumour expressing the target at concentration levels expected in early stage colorectal cancer. Tumours were grown subcutaneously. The imaging agent was administered intravenously at a dose of 50nmol/kg body weight. The animals were killed 2 hours post administration and prepared for imaging. A 3-4mm diameter, 1.6mm thick slice of viable tumour was placed over the opened colon and imaged with the laparoscope system. A receiver operator characteristic analysis was applied to imaging results. An area under the curve of 0.98 and a sensitivity of 87% [73, 96] and specificity of 100% [93, 100] were obtained.

Proceedings Article | 11 July 2007 Paper

Molecular targeting as a contrast agent mechanism for fluorescence endoscopy

A. Healey, R. Bendiksen, A. Tornes, E. Johannesen

Proceedings Volume 6626, 66260F (2007) https://doi.org/10.1117/12.728261

KEYWORDS: Luminescence, Imaging systems, Laparoscopy, Molecules, Optical filters, Signal to noise ratio, Endoscopy, Tissues, Charge-coupled devices, Spatial resolution

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Several mechanisms of action can be employed for a molecular imaging contrast agent for use with endoscopy. Targeting of cell surface molecules that are up regulated at an early disease stage, with a fluorescent labelled vector is one attractive approach. However, it suffers from the inherent limitation that the concentration of agent available is fundamentally limited by the concentration of receptor molecules available. Simple models indicate that for successful imaging with a targeting approach, the imaging system should be able to adequately image concentrations in the nanomolar region. Such low reporter molecule concentrations have implications for the choice of contrast agent. Target tissue size and location, the tissue native fluorescence contribution, the brightness of the reporter molecule, and photobleaching thresholds are all factors which contribute to the choice of reporter. For endoscopic imaging of millimetre sized target tissue volumes close to the surface Cy5^TM (650-700nm) wavelengths are preferable to Cy3^TM (550-600nm) and Cy7^TM (750-800nm). We have constructed a system optimised for sensitivity by tailoring light delivery, collection, filtering and detection, in order to address the fundamental technical performance limits for endoscopic applications. It is demonstrated through imaging system calibration, phantom based measurement and animal imaging data that low nanomolar concentrations of Cy5 based fluorescent contrast agent in millimetre sized superficial lesions are adequately imaged with a clinically relevant endoscope system in real time. It is concluded that targeting is a technically viable approach for endoscopic applications.

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