In vivo near-infrared fluorescence imaging of osteoblastic activity.
In vertebrates, the development and integrity of the skeleton requires hydroxyapatite (HA) deposition by osteoblasts. HA deposition is also a marker of, or a participant in, processes as diverse as cancer and atherosclerosis. At present, sites of osteoblastic activity can only be imaged in vivo using 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 derivative that exhibits rapid and specific binding to HA in vitro and in vivo. We demonstrate NIR light-based detection of osteoblastic activity in the living animal, and discuss how this technology can be used to study skeletal development, osteoblastic metastasis, coronary atherosclerosis, and other human diseases.
Zaheer
A
A
Department of Radiology, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
Lenkinski
R E
RE
Mahmood
A
A
Jones
A G
AG
Cantley
L C
LC
Frangioni
J V
JV
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D001672:Biocompatible Materials / Q000494:pharmacology; D004164:Diphosphonates / Q000138:chemical synthesis / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D017886:Durapatite / Q000494:pharmacology; D005456:Fluorescent Dyes / Q000493:pharmacokinetics / Q000494:pharmacology*; D006801:Humans; D007700:Kinetics; D008279:Magnetic Resonance Imaging; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008856:Microscopy, Fluorescence / Q000379:methods*; D008956:Models, Chemical; D010006:Osteoblasts / Q000166:cytology* / Q000378:metabolism; D000077268:Pamidronate; D011485:Protein Binding; D013667:Technetium; D013997:Time Factors
D000970:Antineoplastic Agents; D001672:Biocompatible Materials; D004164:Diphosphonates; D005456:Fluorescent Dyes; D013667:Technetium; D017886:Durapatite; D000077268:Pamidronate