Considerations in the selection of radiopharmaceuticals for palliation of bone pain from metastatic osseous lesions

Bone pain is a common complication for terminal patients with bone metastas es from prostate, lung, breast, and other malignancies. A multidisciplinary approach in treating bone pain is generally required, 1 which includes a c ombination of analgesic drug therapy, radiation therapy, hormonal therapy, and chemotherapy. Over the years, treatment of bone pain using bone-seeking radiopharmaceuticals has been explored extensively. Pharmaceuticals labele d with energetic beta-particle emitters such as P-32, Sr-89, Sm-153, and Re -186, in addition to the low-energy electron emitter Sn-117m, have been stu died for this purpose. Bone-marrow toxicity as a consequence of chronic irr adiation by the energetic beta particles is a general problem associated wi th this form of treatment. It is therefore desirable to identify radiochemi cals that minimize the dose to the bone marrow and at the same time deliver therapeutic doses to the bone. Methods: New S values (mean absorbed dose p er unit cumulated activity) for target regions of human bone and marrow wer e used to ascertain the capacity of various radiochemicals to deliver a hig h bone dose while minimizing the marrow dose. The relative dosimetric advan tage of a given radiopharmaceutical compared with a reference radiochemical was quantitated as a dosimetric relative advantage factor (RAF). Several r adionuclides that emit energetic beta particles (P-32, Sr-89, Sm-153, Re-18 6, and Lu-177) and radionuclides that emit low-energy electrons or beta par ticles (Er-169. (117)mSn, and P-33) were evaluated. For these calculations, ratios of the cumulated activity in the bone relative to cumulated activit y in the marrow alpha equal to 10 and 100 were used. Results: When the radi opharmaceutical was assumed to be uniformly distributed in the endosteum an d alpha was taken as 100 for both the reference and test radiochemicals, th e RAF values compared with the reference radionuclide P-32 were 1.0, 1.2, 1 .4, 1.6, 1.7, 1.9, and 2.0 for Sr-89, Re-186, Sm-153, Lu-177, Er-169, Sn-11 7m, and P-33, respectively. In contrast, when the radiopharmaceutical is as sumed to be uniformly distributed in the bone volume, the RAF values for th ese 7 radionuclides were 1.1, 1.5, 2.4, 3.2, 4.5, 5.1, and 6.5, respectivel y. Conclusion: These results suggest that low-energy electron emitters such as Sn-117m and P-33 are more likely to deliver a therapeutic dose to the b one while sparing the bone marrow than are energetic beta emitters such as P-32 and Sr-89. Therefore, radiochemicals tagged with low-energy electron o r beta emitters are the radiopharmaceuticals of choice for treatment of pai nful metastatic disease in bone.