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Intraorgan Biodistribution and Dosimetry of ¹⁵³Sm-Ethylenediaminetetramethylene Phosphonate in Juvenile Rabbit Tibia: Implications for Targeted Radiotherapy of Osteosarcoma

¹ Department of Veterinary Medicine and Surgery, University of Missouri-Columbia, Columbia, Missouri
² Department of Radiology, University of Missouri-Columbia, Columbia, Missouri
³ Nuclear Science and Engineering Institute, University of Missouri-Columbia, Columbia, Missouri

Targeted radiotherapy using ¹⁵³Sm-ethylenediaminetetramethylene phosphonate (¹⁵³Sm-EDTMP) is currently under investigation for treatment of primary osteosarcoma. Human osteosarcoma most frequently occurs in skeletally immature individuals, and previous studies in a juvenile rabbit model demonstrated that clinically significant damage to developing physeal cartilage might occur as a result of systemic ¹⁵³Sm-EDTMP therapy. The aim of this study was to determine the distribution of ¹⁵³Sm-EDTMP within the tibias of juvenile rabbits and estimate the radiation-absorbed doses delivered to the physeal cartilage. Methods: Eight-week-old New Zealand White rabbits were injected intravenously with 7.57 kBq (280 µCi) of ¹⁵³Sm-EDTMP. At 21 h after injection, the biodistribution of ¹⁵³Sm in the epiphysis, metaphysis, diaphysis, and red marrow of the tibia was obtained. Two-dimensional digital autoradiography was performed on 2-mm sections of tibias for qualitative comparison with the biodistribution data. Self-tissue and cross-tissue absorbed doses were calculated using absorbed fractions generated by the Monte Carlo particle transport code MCNP-4C. Results: The highest uptakes (percentage injected dose per gram [%ID/g] of tissue) of ¹⁵³Sm, 1.99–2.56 %ID/g, were found in the proximal and distal metaphyses, 70%–73% of which localized within 3 mm of the physeal cartilage. The second highest tissues of uptake were the proximal and distal epiphyses, at 0.33–0.62 %ID/g. Digital autoradiography imaging confirmed that the majority of ¹⁵³Sm deposited in the tibia localized to these tissues. Radiation-absorbed doses to the proximal and distal metaphyses were 183 and 130 mGy/MBq, respectively, and those to the proximal and distal epiphyses were 141 and 43.4 mGy/MBq, respectively. These tissues represented the only source compartments contributing to the physeal cartilage doses of 50.0 mGy/MBq for the proximal physis and 39.2 mGy/MBq for the distal physis. Conclusion: The ¹⁵³Sm absorbed doses to the physeal cartilage were consistent with values that can cause dose-limiting damage to rapidly proliferating and differentiating chondrocytes. The pronounced uptake in the juvenile epiphysis indicates that the proliferating zone of the physis can be irradiated from multiple areas, which could increase the expression and degree of radiation damage. Further investigation of the effects of ¹⁵³Sm-EDTMP on immature physeal cartilage is warranted to develop optimized treatment regimens.

Key Words: ¹⁵³Sm-ethylenediaminetetramethylene phosphonate • osteosarcoma • physeal cartilage • absorbed dose

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