In vivo near-infrared fluorescence imaging of osteoblastic activity

In vertebrates, the development and integrity of the skeleton requires hydr oxyapatite (HA) deposition by osteoblasts. HA deposition is also a marker o f, or a participant in, processes as diverse as cancer and atherosclerosis. At present, sites of osteoblastic activity can only be imaged in vivo usin g gamma -emitting radioisotopes. The scan times required are long, and the resultant radioscintigraphic images suffer from relatively low resolution. We have synthesized a near-infrared (NIR) fluorescent bisphosphonate deriva tive that exhibits rapid and specific binding to HA in vitro and in vivo. W e demonstrate NIR light-based detection of osteoblastic activity in the liv ing animal, and discuss how this technology can be used to study skeletal d evelopment, osteoblastic metastasis, coronary atherosclerosis, and other hu man diseases.