Davis Medical Center, University of California, Sacramento, CA, USA.
Semin Nucl Med. 2010 Mar;40(2):136-44. doi: 10.1053/j.semnuclmed.2009.10.005.
Although most patients with locoregional cancer are cured by surgery, radiotherapy, chemotherapy, and combinations thereof, those with distant metastases are not despite systemic chemotherapy. These patients respond to local radiotherapy but generally need systemic therapy. Non-Hodgkin's lymphoma (NHL) provides a paradigm for the role of molecular targeted radiotherapy (MTRT) because these patients have multifocal disease in most cases. Although patients with NHL achieve remissions after multiple cycles of chemotherapy, less than one half of those with aggressive NHL are cured and almost none of those with low grade NHL. Furthermore, NHL, like other cancers, becomes chemoresistant, yet remains responsive to radiotherapy. MTRT, radiation targeted by molecules, is a good strategy for the treatment of multifocal and radiosensitive cancers. Radioimmunotherapy (RIT) is an MTRT approach using MAbs, or parts thereof, to target the radionuclide that delivers radiation. Two anti-CD20 monoclonal antibodies (MAbs), one labeled with (111)In for imaging or (90)Y for therapy and a second labeled with (131)I for imaging and therapy, have proven effective and safe for MTRT for NHL patients. The importance of the radiation is demonstrated in the data from the randomized pivotal trial of (90)Y-ibritumomab; response rates were distinctly better in the (90)Y-ibritumomab arm than in the rituximab arm. Furthermore, the efficacy of (131)I-tositumomab was greater than that of the same MAb alone in another pivotal trial. Although hematologic toxicity is dose limiting for MTRT, febrile neutropenia is uncommon. MTRT is also not associated with mucositis, hair loss, or persistent nausea or vomiting, unlike chemotherapy. Randomized trials of MTRT in different strategies have not been conducted, but there is evidence of better outcomes, particularly for strategies that provide dose intensification, such as pretargeted MTRT, multiple dosing ("fractionation"), and MTRT with stem cell transplantation (SCT). Pretargeted RIT separates delivery of the targeting molecule from radionuclide delivery, provides dose escalation, and is more effective than direct one-step RIT, although more complicated to implement. Improved drugs and strategies for MTRT have documented potential for better patient outcomes. Smaller radionuclide carriers, such as those used for pretargeted MTRT, should be incorporated into the management of patients with NHL and other cancers soon after the patients have proven incurable. Expected improvements using better drugs, strategies, and combinations with other drugs seem likely to make MTRT integral in the management of many patients with cancer and likely to lead to cures of NHL.
虽然大多数局部区域癌症患者可以通过手术、放疗、化疗以及它们的联合治疗得到治愈，但存在远处转移的患者则无法治愈，即使进行全身化疗也不行。这些患者对局部放疗有反应，但通常需要全身治疗。非霍奇金淋巴瘤（NHL）为分子靶向放疗（MTRT）的作用提供了范例，因为这些患者在大多数情况下都有多发性疾病。尽管 NHL 患者在多次化疗周期后会缓解，但不到一半的侵袭性 NHL 患者被治愈，几乎没有低级别 NHL 患者被治愈。此外，与其他癌症一样，NHL 会产生化疗耐药性，但仍对放疗有反应。MTRT 是一种针对多灶性和放疗敏感癌症的好策略，它通过分子靶向放疗。放射性免疫疗法（RIT）是一种 MTRT 方法，使用 MAbs 或其部分来靶向传递辐射的放射性核素。两种抗 CD20 单克隆抗体（MAb），一种用 (111)In 进行成像或 (90)Y 进行治疗，另一种用 (131)I 进行成像和治疗，已被证明对 NHL 患者的 MTRT 既有效又安全。从 (90)Y-ibritumomab 的随机关键试验数据中可以看出辐射的重要性；在 (90)Y-ibritumomab 组中，缓解率明显优于利妥昔单抗组。此外，在另一项关键试验中，(131)I-tositumomab 的疗效优于相同的 MAb 单独使用。尽管血液学毒性是 MTRT 的剂量限制因素，但发热性中性粒细胞减少症并不常见。与化疗不同，MTRT 也不会引起粘膜炎、脱发或持续的恶心或呕吐。不同策略的 MTRT 随机试验尚未进行，但有证据表明，特别是对于提供剂量强化的策略，如靶向 MTRT、多次给药（“分割”）和 MTRT 与干细胞移植（SCT）相结合，结果更好。预靶向 RIT 将靶向分子的传递与放射性核素的传递分开，提供剂量递增，并比直接一步 RIT 更有效，尽管实施起来更复杂。改进的药物和 MTRT 策略已证明有可能改善患者的预后。较小的放射性核素载体，如用于预靶向 MTRT 的载体，应在患者被证明无法治愈后尽快纳入 NHL 和其他癌症患者的管理中。使用更好的药物、策略以及与其他药物联合使用的组合的预期改进似乎很有可能使 MTRT 成为许多癌症患者管理的重要组成部分，并可能导致 NHL 的治愈。
