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Biologic Mechanisms of ⁸⁹SrCl₂ Incorporation into Type I Collagen During Bone Mineralization

Nycomed Amersham plc, Imaging Research and Development, Ainersham Laboratories, Amersham
Amersham Pharmacia Biotech, Research and Development, Cardiff Laboratories, Cardiff United Kingdom

Correspondence: For correspondence or reprints contact: Richard J. Pither, PhD, Nycomed Amersham plc, White Lion Rd., Amersham, Bucks HP7 9LL, UK.

ABSTRACT

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 adenocarcinomacell 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. Conclusion: ⁸⁹SrCl₂ acts as a calcium mimic and, as such, becomes associated with the collagen matrix produced by the MC3T3-E1 cells during collagen mineralization.

Key Words: bone mineralization • bone neoplasms • collagen • radiopharmaceutical • strontium radioisotope