1 Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center , Omaha, Nebraska.
Cancer Biother Radiopharm. 2013 Nov;28(9):639-50. doi: 10.1089/cbr.2013.1523. Epub 2013 Jul 11.
Due to its ability to target both known and occult lesions, radioimmunotherapy (RIT) is an attractive therapeutic modality for solid tumors. Poor tumor uptake and undesirable pharmacokinetics, however, have precluded the administration of radioimmunoconjugates at therapeutically relevant doses thereby limiting the clinical utility of RIT. In solid tumors, efficacy of RIT is further compromised by heterogeneities in blood flow, tumor stroma, expression of target antigens and radioresistance. As a result significant efforts have been invested toward developing strategies to overcome these impediments. Further, there is an emerging interest in exploiting short-range, high energy α-particle emitting radionuclides for the eradication of minimal residual and micrometastatic disease. As a result several modalities for localized therapy and models of minimal disease have been developed for preclinical evaluation. This review provides a brief update on the recent efforts toward improving the efficacy of RIT for solid tumors, and development of RIT strategies for minimal disease associated with solid tumors. Further, some of promising approaches to improve tumor targeting, which showed promise in the past, but have now been ignored are also discussed.
由于其能够靶向已知和隐匿性病变,放射性免疫治疗(RIT)是实体瘤有吸引力的治疗方式。然而,较差的肿瘤摄取和不理想的药代动力学特性,使得放射性免疫偶联物无法以治疗相关剂量给药,从而限制了 RIT 的临床应用。在实体瘤中,RIT 的疗效进一步受到血流、肿瘤基质、靶抗原表达和放射抗性的异质性的影响。因此,人们投入了大量精力来开发克服这些障碍的策略。此外,人们对利用短程、高能α粒子发射放射性核素来根除微小残留和微转移疾病产生了浓厚兴趣。因此,已经开发了几种局部治疗模式和最小疾病模型,用于临床前评估。本综述简要介绍了最近为提高 RIT 治疗实体瘤的疗效以及开发与实体瘤相关的最小疾病的 RIT 策略所做的努力。此外,还讨论了一些有前途的方法来改善肿瘤靶向,这些方法在过去曾显示出前景,但现在已被忽视。
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