Marrow-sparing effects of 117mSn(4+)diethylenetriaminepentaacetic acid for radionuclide therapy of bone cancer.
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 beta 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 gamma-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 beta emitter 32P.


CONCLUSIONS
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.
Bishayee
A
A
Department of Radiology, University of Medicine and Dentistry of New Jersey-New Jersey Medical School, Newark 07103, USA.
Rao
D V
DV
Srivastava
S C
SC
Bouchet
L G
LG
Bolch
W E
WE
Howell
R W
RW
D000818:Animals; D001853:Bone Marrow / Q000528:radiation effects*; D001859:Bone Neoplasms / Q000532:radiotherapy*; D005260:Female; D006801:Humans; D051379:Mice; D004369:Pentetic Acid / Q000627:therapeutic use*; D011829:Radiation Dosage; D019275:Radiopharmaceuticals / Q000627:therapeutic use*; D014004:Tin Radioisotopes / Q000627:therapeutic use*
D019275:Radiopharmaceuticals; D014004:Tin Radioisotopes; D004369:Pentetic Acid