Abstract 2649: Whole body vibration effects on binding kinetics and targeting of near-infrared dye conjugated bisphosphonate

Proceedings: AACR 101st Annual Meeting 2010‐‐ Apr 17‐21, 2010; Washington, DC A non-invasive means of targeting bisphophonate to specific skeletal sites, along with the passive binding/decay kinetics of the near-infrared bisphosphanate analog to the skeleton are determined. Bone is the third common site where breast, lung, and prostate cancer cells spread and metastasize. Debilitating pain is the major complication resulting from bone metastases in nearly 70% of the patients. The palliative bone pain management includes the bisphosphanate therapy. Bisphosphonates, a potent inhibitor of bone resorption, gives both pain relief and improves bone health. However these medications result in complications such as bisphosphonate-related osteonecrosis of the jaw (BRONJ). Combinations of low-risk exercise programs along with reduced drug dosage are a likely alternative to counter such drug-related side effects. Site-selective skeletal targeting of bisphosphonates, if feasible, is however ideal to overcome drug-related side effects. We utilized whole body vibration (WBV), to target NIR dye conjugate bisphosphonate to specific skeletal sites. Using near-infrared (NIR) fluorescence imaging, both the targeting and the passive binding of the bisphosphonate in vivo was determined. Vibration loading, utilizing whole body vibration (WBV) was performed on twelve mice by subjecting them to vibration frequency of 35 Hz for fifteen min (5-10 times/week) duration. Alendronate was conjugated to near-infrared tricarbocyanine, cyclic enamine-functionalized dye, and was injected intravenously after 21-day exercise regime. Yet to be reported, we show that NIR-alendronate probe bound to the lumbar L6 vertebrae, resultant of direct high-frequency WBV stimulation. This is besides several other specific targeting sites. Further, both the passive binding and the decay kinetics of the NIR signal at the skeleton was determined in a six-week non-invasive longitudinal study of mouse pups. This provides opportunity to utilize such approaches in future translational studies in assessing the role of bisphosphonates in preventing spreading of cancer cells at other secondary sites, especially bone. The targeted drug binding in response to the vibratory protocol also provides hope in the development of whole body vibration (WBV) as a bisphosphonate-therapeutic aid. Further, to develop strategies in reducing the drug dosage in treatment of other morbidity factors that stem from complications from bone metastases. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2649.