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Considerations in the Selection of Radiopharmaceuticals for Palliation of Bone Pain from Metastatic Osseous Lesions

Department of Nuclear and Radiological Engineering, University of Florida, Gainesville, Florida
Department of Radiology, University of Medicine and Dentistry of New Jersey-New Jersey Medical School, Newark, New Jersey

Correspondence: For reprints or correspondence contact: Dandamudi V. Rao, PhD, Department of Radiology, MSB F-451, UMDNJ-New Jersey Medical School, 185 S. Orange Ave., Newark, NJ 07103.

ABSTRACT

Bone pain is a common complication for terminal patients with bone metastases from prostate, lung, breast, and other malignancies. A multidisciplinary approach in treating bone pain is generally required, 1 which includes a combination 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 labeled with energetic p-particle emitters such as ³²P, ⁸⁹Sr, ¹⁵³Sm, and ¹⁸⁶Re, in addition to the low-energy electron emitter ^117mSn, have been studied for this purpose. Bone-marrow toxicity as a consequence of chronic irradiation by the energetic ß particles is a general problem associated with this form of treatment. It is therefore desirable to identify radiochemicals 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 per unit cumulated activity) for target regions of human bone and marrow were used to ascertain the capacity of various radiochemicals to deliver a high bone dose while minimizing the marrow dose. The relative dosimetric advantage of a given radiopharmaceutical compared with a reference radiochemical was quantitated as a dosimetric relative advantage factor (RAF). Several radionuclides that emit energetic ß particles (³²P, ⁸⁹Sr, ¹⁵³Sm, and ¹⁸⁶Re, and ¹⁷⁷Lu) and radionuclides that emit low-energy electrons or ß particles (¹⁶⁹Er, ^117mSn, and ³³P) were evaluated. For these calculations, ratios of the cumulated activity in the bone relative to cumulated activity in the marrow equal to 10 and 100 were used. Results: When the radiopharmaceutical was assumed to be uniformly distributed in the endosteum and was taken as 100 for both the reference and test radiochemicals, the RAF values compared with the reference radionuclide ³²P were 1.0, 1.2, 1.4, 1.6, 1.7, 1.9, and 2.0 for ⁸⁹Sr, ¹⁸⁶Re, ¹⁵³Sm, ¹⁷⁷Lu, ¹⁶⁹Er, ^117mSn, and ³³P, respectively. In contrast, when the radiopharmaceutical is assumed to be uniformly distributed in the bone volume, the RAF values for these 7 radionuclides were 1.1, 1.5, 2.4, 3.2, 4.5, 5.1, and 6.5, respectively. Conclusion: These results suggest that low-energy electron emitters such as ^117mSn and ³³P are more likely to deliver a therapeutic dose to the bone while sparing the bone marrow than are energetic ß emitters such as ³²P and ⁸⁹Sr. Therefore, radiochemicals tagged with low-energy electron or ß emitters are the radiopharmaceuticals of choice for treatment of painful metastatic disease in bone.

Key Words: bone pain • radionuclide therapy • dosimetry

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