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Marrow-Sparing Effects of ^117mSn(4+)Diethylenetriaminepentaacetic Acid for Radionuclide Therapy of Bone Cancer

Division of Radiation Research, Department of Radiology, University of Medicine and Dentistry of New Jersey–New Jersey Medical School, Newark, New Jersey; Medical Department, Brookhaven National Laboratory, Upton, New York; and Department of Nuclear and Radiological Engineering, University of Florida, Gainesville, Florida

Several bone-seeking radionuclides (³²P, ⁸⁹Sr, ¹⁸⁶Re, and ¹⁵³Sm) have been used to treat bone pain. The limiting factor in this modality is marrow toxicity. Our hypothesis is that marrow toxicity can be reduced while maintaining therapeutic efficacy using radionuclides that emit short-range ß particles or conversion electrons (CEs). A recent study on 47 patients using the short-range CE emitter ^117mSn(4+)diethylenetriaminepentaacetic acid (^117mSn(4+)DTPA) supports this hypothesis. The hypothesis is now tested using ^117mSn(4+)DTPA in a mouse femur model. Methods: The survival of granulocyte–macrophage colony-forming cells (GM-CFCs) in femoral marrow is used as a biologic dosimeter for bone marrow. The dosimeter is calibrated by irradiating mice with exponentially decreasing dose rates of ¹³⁷Cs -rays with a dose-rate decrease half-time, T_d, equal to the effective clearance half-time of ^117mSn(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 cGy. After calibration, ^117mSn(4+)DTPA is administered and GM-CFC survival is determined as a function of injected activity. These data are used to experimentally determine the mean absorbed dose to the femoral marrow per unit injected activity. The kinetics of radioactivity in the marrow, muscle, and femoral bone are also determined. Finally, a theoretic dosimetry model of 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 femoral marrow per unit injected activity of ^117mSn(4+)DTPA is 0.043 cGy/kBq. The theoretic mean absorbed dose to the femoral bone per unit injected activity is 1.07 cGy/kBq. If these data are compared with those obtained previously for ³²P-orthophosphate, the radiochemical ^117mSn(4+)DTPA yields up to an 8-fold therapeutic advantage over the energetic ß emitter ³²P. Conclusion: The CE emitter ^117mSn offers a large dosimetric advantage over energetic ß-particle emitters for alleviating bone pain, and possibly for other therapeutic applications, while minimizing marrow toxicity.

Key Words: bone • pain • metastases • radionuclides • granulocyte–macrophage colony-forming cells • chronic irradiation • dose–response • dosimetry • EGS4 • ³²P • ³³P • ^117mSn • therapy

Received Dec. 28, 1999; revision accepted May 30, 2000.

For correspondence or reprints contact: Roger W. Howell, PhD, Department of Radiology, MSB F-451, UMDNJ–New Jersey Medical School, 185 S. Orange Ave., Newark, NJ 07103.

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