Chopra Arvind
National Center for Biotechnology Information, NLM, NIH, Bethesda, MD 20894
Due to the metastases of cancer in the skeletal tissue, severe bone pain affects the quality of life of most patients suffering from malignancies of the breast, prostate, lungs, thyroid, or kidneys (2, 3). Although several interventions such as analgesics, bisphosphonates, hormone therapy, and systemic radionuclide therapy are available to manage the pain, these treatments are known to have many undesirable secondary effects (3). Radiopharmaceuticals that contain nuclides, such as strontium-89 (as SrCl) and samarium-153 (administered as Sm-ethylenediamine tetramethylene phosphonic acid (EDTMP)), which are commonly used for palliative care of pain in the bones of these cancer patients, have been approved by the United States Food and Drug Administration (FDA) for the treatment of this condition (3). However, these are not the most ideal agents to treat pain due to bone metastases because the radionuclide either has a long half-life and generates high-energy β particles (Sr has a half-life of ~50 days and = 1.49 MeV) or is short-lived and has to be produced in close vicinity to the treatment center (Sm has a half-life of ~47 h, = 0.81 MeV, and γ = 103 keV (28%)) (2). In addition, both of these bone pain palliative agents are known to produce myelotoxicity in some patients (4). Between the two labeled compounds, SrCl appears to be the agent of choice for clinical applications because of its longer half-life, which provides the flexibility to develop a suitable treatment regimen for the patient. There is much interest to develop alternative radiolabeled compounds that do not suppress the bone marrow but are suitable to treat pain resulting from osseous metastases as discussed by Jansen et al. (4). Recently, Das et al. evaluated the use of thulium-170 (Tm has a half-life of ~128 days, = 968 keV, and γ = 84 keV (3.26%)) as an alternative to SrCl for the development of a bone pain palliative (2). According to these investigators, Tm would probably exhibit low myelosupression because it emits β particles of lower energy than those emitted by Sr, and the γ-photons generated by the nuclide can be used for scintigraphy to detect the accumulation and location of the radiolabel in the organs of an animal. This chapter describes the biodistribution of Tm-labeled EDTMP (Tm-EDTMP) in normal Wistar rats (2).
由于癌症转移至骨骼组织，严重的骨痛影响了大多数患有乳腺癌、前列腺癌、肺癌、甲状腺癌或肾癌的患者的生活质量（2, 3）。尽管有多种干预措施，如镇痛药、双膦酸盐、激素疗法和全身放射性核素疗法可用于控制疼痛，但已知这些治疗有许多不良副作用（3）。含有锶-89（如氯化锶）和钐-153（以钐-乙二胺四甲基膦酸（EDTMP）形式给药）等核素的放射性药物，常用于这些癌症患者骨骼疼痛的姑息治疗，已被美国食品药品监督管理局（FDA）批准用于治疗这种疾病（3）。然而，这些并非治疗骨转移引起疼痛的最理想药物，因为放射性核素要么半衰期长且产生高能β粒子（锶的半衰期约为50天，β = 1.49 MeV），要么半衰期短且必须在治疗中心附近生产（钐的半衰期约为47小时，β = 0.81 MeV，γ = 103 keV（28%））（2）。此外，已知这两种骨痛姑息治疗药物在一些患者中会产生骨髓毒性（4）。在这两种标记化合物中，氯化锶因其较长的半衰期，似乎是临床应用的首选药物，这为为患者制定合适的治疗方案提供了灵活性。正如扬森等人（4）所讨论的，人们对开发不抑制骨髓但适合治疗骨转移引起疼痛的替代放射性标记化合物很感兴趣。最近，达斯等人评估了使用铥-170（铥的半衰期约为128天，β = 968 keV，γ = 84 keV（3.26%））作为氯化锶的替代品来开发骨痛姑息治疗药物（2）。根据这些研究人员的说法，铥可能表现出低骨髓抑制作用，因为它发射的β粒子能量低于锶发射的β粒子，并且该核素产生的γ光子可用于闪烁扫描，以检测放射性标记在动物器官中的积累和位置。本章描述了铥标记的EDTMP（铥-EDTMP）在正常Wistar大鼠体内的生物分布（2）。
