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LI-COR Introduces New Bone Marker for Cancer Research

April 4, 2008, Lincoln, NE: Now Available: IRDye® 680 BoneTag™ and IRDye 800CW BoneTag are calcium-chelating compounds conjugated to either IRDye 680 or IRDye 800CW NIR dyes. Use of IRDye NIR dyes extends fluorescence signal detection to the NIR region of the spectrum without affecting the compound's ability to function as a marker of the mineralization process. NIR fluorescence detection improves depth of penetration due to low tissue autofluorescence, translating to low background interference.

The ability to visualize bone anatomy and structures for an extended period facilitates use of the IRDye BoneTag in conjunction with a second optical agent specific for a primary target (i.e, tumor tissue). In addition, IRDye 800CW BoneTag may prove effective for studies dealing with bone metasteses and bone remodeling studies.

Additional information is contained in the following abstract:

Joy L. Kovar, Xinshe Xu, Melanie Simpson, D. Michael Olive
Effective bone labeling for in vivo NIR noninvasive imaging in nude mice
ABSTRACT: Calcium-chelating compounds have been used effectively for the detection of bone mineralization, growth, and morphological changes, including tetracycline derivatives, xylenol orange, alizarin, calcein, and fluorescein. These compounds contain iminodiacetic acid groups that can form chelating complexes with apatite and provide a certain level of native fluorescence in the visible spectrum as the complexes become incorporated in mineralizing bone. We chose to exploit these characteristics to produce a near infrared (NIR) optical bone marker for small animal imaging. By conjugating compounds to IRDye 800CW or IRDye 680, we have extended the effective fluorescence signal detection to the NIR region without affecting the compound's ability to function as a marker of the mineralization process. Initial screening of multiple compounds was performed using MC3T3-E1 (osteoblasts) in an in vitro cell-based assay. Two of the seven compounds exhibited signal intensities approximately 3–6X higher than the others. Subsequent in vivo testing of Compounds A and F demonstrated effective skeletal labeling for imaging which is unabated several weeks post-administration. The ability to visualize bone anatomy/structures for an extended period will facilitate use of the bone targeting agent in conjunction with a second optical agent specific for a primary target (i.e, tumor tissue). We demonstrate a multiple probe application with the administration of IRDye 680 bone marker one week prior to implantation of prostate tumor cells in the flank of a nude mouse. Animals received weekly intravenous injections of IRDye 800CW 2-deoxyglucose and were imaged 24 hours post-injection over a six-week period, using a prototype small animal imaging system. The results provide evidence that NIR labeled conjugates are useful for multiple probe/localization applications in small animal imaging.



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