有针对性的放射性药物：卵巢癌的未经激动的策略
Targeted radiopharmaceuticals: an underexplored strategy for ovarian cancer
影响因子:13.30000
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
摘要
卵巢癌是全世界最常见的妇科恶性肿瘤，死亡率最高。这种低的存活率可以归因于以下事实：症状仅在晚期疾病阶段出现，其特征是（微）转移性散布在腹膜腔中。放射性药物由靶向部分以及诊断或治疗放射性核素组成，构成了一种相对不受欢迎的溶液方法，可以改善当前的护理标准。有效的患者分层，随访和治疗是几种警告，可以用Theranostics解决，以改善患者的预后。到目前为止，大部分研究都位于临床前的水平，通常采用原发性和转移性腹膜疾病的鼠模型，这些模型不一定提供疾病异质性的准确表示（内在的）耐药性或与肿瘤微环境的复杂生理相互作用。带有治疗性α和电子发射放射性核素的放射免疫偶联物已成为流行的标准，其靶向了各种卵巢癌的各种异质组织学亚型表达的无数细胞膜标记。显然，临床前研究中存在一些障碍，这些障碍可能会阻止这些药物前进到临床实践中。另一方面，核医学领域还看到了重大的创新，以解决与目标/配体识别，临床前研究模型，放射化学，放射性药物和剂量学相关的缺点，如本综述中所述。总体而言，Theranostics拥有巨大的希望，可以回答对卵巢癌的未满足的医疗需求。
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.