Biologic mechanisms of 89SrCl2 incorporation into type I collagen during bone mineralization.
89SrCl2 is currently used as a palliative treatment for painful osseous metastases associated with an osteoblastic reaction in bone. However, the underlying biologic mechanism by which 89SrCl2 accumulates at these lesions and mediates palliation remains unclear. The aim of this study was therefore to elucidate this mechanism.


METHODS
An in vitro cell biologic model, incorporating the MC3T3-E1 murine osteoblast cell line, was established to replicate the process of collagen production and mineralization. Experiments were performed to investigate the cellular association of 89SrCl2 and 45CaCl2 with both MC3T3-E1 cells and the PC-3 human prostate adenocarcinoma cell line.


RESULTS
No evidence of intracellular localization of 89SrCl2 or 45CaCl2 was found for either cell line. Localization of radiolabel was seen to be associated with MC3T3-E1 cells but only in cultures that had undergone both differentiation and mineralization. The association of 89SrCl2 was inhibited by the alkaline phosphatase inhibitor levamisole, and extracellular localization of 89SrCl2 was confirmed by microautoradiography.


CONCLUSIONS
89SrCl2 acts as a calcium mimic and, as such, becomes associated with the collagen matrix produced by the MC3T3-E1 cells during collagen mineralization.
Davis
J
J
Nycomed Amersham plc, Imaging Research and Development, Amersham Laboratories, United Kingdom.
Cook
N D
ND
Pither
R J
RJ
D000818:Animals; D001859:Bone Neoplasms / Q000532:radiotherapy* / Q000556:secondary; D001842:Bone and Bones / Q000378:metabolism*; D002113:Calcification, Physiologic; D002122:Calcium Chloride / Q000493:pharmacokinetics; D002132:Calcium Radioisotopes / Q000493:pharmacokinetics; D002460:Cell Line; D003094:Collagen / Q000378:metabolism*; D006801:Humans; D008297:Male; D051379:Mice; D010166:Palliative Care; D011471:Prostatic Neoplasms / Q000473:pathology; D013324:Strontium / Q000493:pharmacokinetics* / Q000627:therapeutic use; D013326:Strontium Radioisotopes / Q000493:pharmacokinetics* / Q000627:therapeutic use; D013997:Time Factors; D014407:Tumor Cells, Cultured
D002132:Calcium Radioisotopes; D013326:Strontium Radioisotopes; D003094:Collagen; C025700:strontium chloride; D002122:Calcium Chloride; D013324:Strontium