The severe pain associated with many disorders affecting bone account for a large proportion of cases of patient morbidity, due to the encumbrance of mobility and therefore, compromised quality of life. Skeletal metastasis is one such condition, which generally complicates the treatment of the primary cancers such as that of the breast, prostate and lung - causing intense pain and eventually even mortality. This paper presents examples of various approaches explored and proposed in the ongoing search to identify better radiopharmaceuticals for the treatment of bone disorders such as metastases. The primary objective of these developments is to alleviate the debilitating pain commonly associated with bone lesions. The efficacy of a radiotherapeutic agent intended for the treatment of diseased bone is particularly dependent on the radiation dose to the tumor cells and on the extent to which suppression of bone marrow or other critical organs can be avoided. Therefore, the design rationale requires careful consideration of the choice radionuclide and especially ensuring that the drug selectively targets the lesion or tumor site. The options pursued include the use of radioisotopes with an intrinsic affinity for bone, such as 89Sr or 223Ra, or the design of bone-seeking ligands, such as phosphonates, to selectively deliver the radionuclide to the target, e.g. [153Sm]Sm-EDTMP. A combination of the above may too be possible, where the bone seeking ligand facilitates the selective accumulation of a radionuclide, which by itself is also bone homing. In terms of therapeutic application radionuclides with various decay modes are proposed, including beta (β-) emitters: 153Sm, 89Sr, 186Re, 188Re, 32P, 177Lu and 170Tm; alpha (α) emitters: 223Ra and 225Ra; and Auger or conversion electron emitter: 117mSn. From a purely diagnostic perspective, the radioisotopes used for imaging include the well known photon emitting 99mTc, and positron emitters 18F and 68Ga. The current status in the development and application of internal radiotherapy for the palliative treatment of bone pain will be discussed, summarizing the progress made and challenges encountered in the process to realizing an effective drug candidate.
Keywords: Bone-seeking, radiopharmaceutical, metastasis, bone targeting, bone-pain palliation, hormone-refractory prostate cancer, Radiotherapy, Bone Malignancies, Skeletal metastasis, cancers, radiopharmaceuticals, bone lesions, radiation dose, radiotherapeutic agent, bone marrow, radionuclide, tumor cells, [153Sm]Sm-EDTMP, phosphonates, beta emitters, photon emitting, vertebrate, calcium, osteoporosis, osteosarcoma, hematological malignancies, multiple myeloma, non-Hodgkin lymphoma, cytokines, osteoclast activity, osteolysis, vicious cycle, pain palliative therapy, analgesia, prostaglandins, neurogenic peptides, chelators, anti-tumor effect, hydroxyapatite, strontium, pyrophosphate, Quadramet, neutron fluxes, Good Manufacturing Practice, cyclotron-driven neutron activators, -camera scintigraphy, single photon emission tomography, gamma rays, Chemotherapy, 177Lu-Labeled Phosphonates, 170Tm-labeled EDTMP
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