Marrow-sparing effects of Sn-117m(4+)diethylenetriaminepentaacetic acid for radionuclide therapy of bone cancer

Several bone-seeking radionuclides (P-32, Sr-89, Re-186, and Sm-153) have b een used to treat bone pain. The limiting factor in this modality is marrow toxicity. Our hypothesis is that marrow toxicity can be reduced while main taining therapeutic efficacy using radionuclides that emit short-range beta particles or conversion electrons (CEs). A recent study on 47 patients usi ng the short-range CE emitter Sn-117m(4+)diethylenetriaminepentaacetic acid (117mSn(4+)DTPA) supports this hypothesis. The hypothesis is now tested us ing 117mSn(4+)DTPA in a mouse femur model. Methods: The survival of granulo cyte-macrophage colony-forming cells (GM-CFCs) in femoral marrow is used as a biologic dosimeter for bone marrow. The dosimeter is calibrated by irrad iating mice with exponentially decreasing dose rates of Cs-137 gamma -rays with a dose-rate decrease half-time, T-d, equal to the effective clearance half-time of Sn-117m(4+)DTPA from the femur (222 h). When T-d = 222 h, the mean absorbed dose required to achieve a survival fraction of 37% is 151 cG y. After calibration, (117)mSn(4+)DTPA is administered and GM-CFC survival is determined as a function of injected activity. These data are used to ex perimentally determine the mean absorbed dose to the femoral marrow per uni t injected activity. The kinetics of radioactivity in the marrow, muscle, a nd femoral bone are also determined. Finally, a theoretic dosimetry model o f the mouse femur is used, and the absorbed doses to the femoral marrow and bone are calculated. Results: The experimental mean absorbed dose to the f emoral marrow per unit injected activity of Sn-117m(4+)DTPA is 0.043 cGy/kB q. The theoretic mean absorbed dose to the femoral bone per unit injected a ctivity is 1.07 cGy/kBq. If these data are compared with those obtained pre viously for P-32-orthophosphate, the radiochemical (117)mSn(4+)DTPA yields up to an 8-fold therapeutic advantage over the energetic beta emitter P-32. Conclusion: The CE emitter 117mSn offers a large dosimetric advantage over energetic beta -particle emitters for alleviating bone pain, and possibly for other therapeutic applications, while minimizing marrow toxicity.