Review

靶向放射药物：卵巢癌中未充分探索的策略

Targeted radiopharmaceuticals: an underexplored strategy for ovarian cancer

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Theranostics

影响因子:13.3

分区:医学1区 Top / 医学：研究与实验1区

发表日期:2024

作者: Melissa Crabbé, Tomas Opsomer, Koen Vermeulen, Maarten Ooms, Charlotte Segers

DOI: 10.7150/thno.99782

摘要

卵巢癌是全球最常见的妇科恶性肿瘤，具有最高的死亡率。其低生存率主要由于症状通常在晚期出现，表现为腹腔内微转移。放射药物由靶向分子与诊断或治疗性放射性核素结合组成，是一种相对未被充分研究的治疗诊断一体化策略，有望改善现有的治疗标准。高效的患者分层、随访和治疗是该策略可以解决的若干难题。目前，大部分研究仍停留在临床前阶段，采用小鼠模型模拟原发性和转移性腹腔疾病，这些模型未必能准确反映疾病的异质性、（固有的）耐药性或与肿瘤微环境的复杂相互作用。治疗性α和电子发射放射性核素的放射免疫偶联物已成为主要标准，靶向卵巢癌各种异质性组织类型中表达的多种细胞膜标志物。显然，临床前研究中存在多重障碍，可能阻碍这些药物的临床应用。此外，核医学领域也在不断创新，以应对靶点/配体识别、临床前模型、放射化学、放射药剂学和剂量学方面的不足。本综述总结了这些创新，并指出治疗诊断策略在满足卵巢癌未被满足的医疗需求方面具有巨大潜力。

Abstract

Ovarian cancer is the most common gynecological malignancy worldwide with the highest mortality. This low survival rate can be attributed to the fact that symptoms arise only at an advanced disease stage, characterized by a (micro)metastatic spread across the peritoneal cavity. Radiopharmaceuticals, composed of a targeting moiety coupled with either a diagnostic or therapeutic radionuclide, constitute a relatively underexplored theranostic approach that may improve the current standard of care. Efficient patient stratification, follow-up and treatment are several caveats that could be addressed with theranostics to improve patient outcomes. So far, the bulk of research is situated and often halted at the preclinical level, employing murine models of primary and metastatic peritoneal disease that do not necessarily provide an accurate representation of the disease heterogeneity, (intrinsic) drug resistance or the complex physiological interactions with the tumor microenvironment. Radioimmunoconjugates with therapeutic α- and electron-emitting radionuclides have been the prevailing standard, targeting a myriad of cell-membrane markers that are expressed in the various heterogeneous histological subtypes of ovarian cancer. Evidently, several hurdles exist within preclinical research that are potentially withholding these agents from advancing into clinical practice. On the other hand, the field of nuclear medicine has also seen significant innovation to address shortcomings related to target/ligand identification, preclinical research models, radiochemistry, radiopharmacy and dosimetry, as outlined in this review. Altogether, theranostics hold great promise to answer an unmet medical need for ovarian cancer.