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Effects of ¹⁵³Sm-Ethylenediaminetetramethylene Phosphonate on Physeal and Articular Cartilage in Juvenile Rabbits

¹ Department of Medicine and Surgery, University of Missouri-Columbia, Columbia, Missouri
² Comparative Orthopaedic Laboratory, University of Missouri-Columbia, Columbia, Missouri
³ Department of Pathobiology, University of Missouri-Columbia, Columbia, Missouri

Previous studies reported that the radiopharmaceutical ¹⁵³Sm-ethylenediaminetetramethylene phosphonate (¹⁵³Sm-EDTMP) is an effective component of multimodality therapy for the treatment of primary bone tumors. Therefore, ¹⁵³Sm-EDTMP may prove to be an integral component of therapy for the treatment of juvenile osteosarcoma. The purpose of this study was to determine the effects of intravenous administration of ¹⁵³Sm-EDTMP on the developing physeal and articular cartilage of healthy, juvenile rabbits. Methods: Sixteen healthy 8-wk-old male New Zealand White rabbits were assigned to 1 of 2 groups: treatment (n = 12) and control (n = 4). ¹⁵³Sm-EDTMP was administered to the treatment group at 37 MBq/kg (1 mCi/kg). The animals were sacrificed at 16 wk of age, and the physeal cartilage of multiple bones was evaluated by use of histologic, immunohistochemical, and histomorphometric analyses. The overall changes in the lengths of the radius and the tibia between control and treatment groups were calculated and compared. Measurement data were combined for each group, and means ± SEMs were determined. Results: Significant differences in radial bone growth were present between the groups. Histologically, the physes of the treatment group were disrupted and chaotic in appearance. Significant differences in the immunoreactivity of type X collagen and matrix metalloproteinase-13 were seen between the groups, as these markers were positively expressed in the zone of hypertrophy of the control rabbits. Conclusion: Clinically significant damage to the developing physeal cartilage may occur as a result of the intravenous administration of ¹⁵³Sm-EDTMP at the dose studied.

Key Words: growth • ¹⁵³Sm-ethylenediaminetetramethylene phosphonate • osteosarcoma • physis • rabbit