Intraorgan biodistribution and dosimetry of 153Sm-ethylenediaminetetramethylene phosphonate in juvenile rabbit tibia: implications for targeted radiotherapy of osteosarcoma.
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 microCi) 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.


CONCLUSIONS
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.
Essman
Stephanie C
SC
Department of Veterinary Medicine and Surgery, University of Missouri-Columbia, Columbia, Missouri 65211, USA. essmans@missouri.edu
Lewis
Michael R
MR
Miller
William H
WH
D018712:Analgesics, Non-Narcotic / Q000494:pharmacology*; D000818:Animals; D001345:Autoradiography; D001853:Bone Marrow / Q000473:pathology; D001842:Bone and Bones / Q000378:metabolism / Q000528:radiation effects; D002356:Cartilage / Q000473:pathology; D008297:Male; D009010:Monte Carlo Method; D009942:Organometallic Compounds / Q000494:pharmacology*; D063065:Organophosphonates / Q000737:chemistry; D009943:Organophosphorus Compounds / Q000494:pharmacology*; D012516:Osteosarcoma / Q000473:pathology* / Q000532:radiotherapy*; D011817:Rabbits; D011868:Radioisotopes / Q000494:pharmacology; D011874:Radiometry / Q000379:methods*; D011877:Radionuclide Imaging; D011879:Radiotherapy Dosage; D013977:Tibia / Q000000981:diagnostic imaging*; D013997:Time Factors; D014018:Tissue Distribution
D018712:Analgesics, Non-Narcotic; D009942:Organometallic Compounds; D063065:Organophosphonates; D009943:Organophosphorus Compounds; D011868:Radioisotopes; C061972:samarium Sm-153 lexidronam