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

Journal of Nuclear Medicine

Roger W. Howell¹  Suresh C. Srivastava¹  Anupam Bishayee¹  Dandamudi V. Rao¹  Wesley E. Bolch¹  Lionel G. Bouchet¹ 

[1] 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 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 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

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

DOI  :  

学科分类：医学（综合）

来源: Society of Nuclear Medicine

【 摘 要 】

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 β 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 γ-rays with a dose-rate decrease half-time, Td, equal to the effective clearance half-time of 117mSn(4+)DTPA from the femur (222 h). When Td = 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 β emitter 32P. Conclusion: The CE emitter 117mSn offers a large dosimetric advantage over energetic β-particle emitters for alleviating bone pain, and possibly for other therapeutic applications, while minimizing marrow toxicity.

【 授权许可】

Unknown