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Combination treatments to enhance peptide receptor radionuclide therapy of neuroendocrine tumours.
European Journal of Nuclear Medicine and Molecular Imaging ( IF 9.1 ) Pub Date : null , DOI: 10.1007/s00259-019-04499-x
Samuel Adant 1, 2, 3, 4 , Girish M Shah 3, 4 , Jean-Mathieu Beauregard 1, 2
Affiliation  

The incidence of neuroendocrine tumours (NETs) is increasing, but curative therapeutic options are limited because diagnosis is often delayed until the tumour has metastasized. Peptide receptor radionuclide therapy (PRRT) is among the most effective therapeutic options for metastatic NETs because of targeted delivery of radioactivity to the tumour via the somatostatin receptor (SSTR) and relatively low systemic toxicity. However, current PRRT regimes result in palliation rather than cure, and higher doses of PRRT that might achieve remission would also be too toxic to the patients. Therefore, there is a need to improve PRRT of NETs by combining it with other agents to achieve maximum benefits from the internal radiation therapy, while sparing non-target organs from radiation toxicity. Here we review various current and potential combination strategies to improve 177Lu-octreotate-based PRRT of NET, some of which could also apply to other radionuclide therapies. These strategies include co-administered drugs that improve delivery of the radiopharmaceutical via increased tumour perfusion or through increased SSTR density at tumour surface. Other combinations are aimed at enhancing the biological effects of the radiation-induced DNA damage in tumour cells or generating additional DNA damage burden to effectively increase the cytotoxicity of PRRT. We also propose an algorithm for stratifying NET patients to receive or not combination therapies with PRRT. Considering that PRRT and many of these combination agents are already used for treating patients with NET and other cancers, the proposed strategies to improve the efficacy of PRRT could be rapidly translated into the clinic.

中文翻译:

联合治疗以增强神经内分泌肿瘤的肽受体放射性核素治疗。

神经内分泌肿瘤(NETs)的发病率正在增加,但是治疗方法的选择有限,因为诊断通常要等到肿瘤转移后才进行。肽受体放射性核素治疗(PRRT)是转移性NET的最有效治疗选择之一,因为通过生长抑素受体(SSTR)将放射性靶向性递送至肿瘤,并且系统毒性相对较低。但是,当前的PRRT方案会导致缓解而不是治愈,并且可能实现缓解的更高剂量的PRRT对患者也有毒。因此,需要通过将NETs与其他药物结合以从内部放射治疗中获得最大收益,同时使非目标器官免受放射毒性,来改善NETs的PRRT。在这里,我们回顾了各种当前和潜在的组合策略,以改善基于177Lu-奥曲肽的NET PRRT,其中一些策略还可应用于其他放射性核素治疗。这些策略包括共同给药的药物,这些药物可通过增加肿瘤灌注或通过增加肿瘤表面的SSTR密度来改善放射性药物的递送。其他组合旨在增强肿瘤细胞中辐射诱导的DNA损伤的生物学效应或产生额外的DNA损伤负担,以有效增加PRRT的细胞毒性。我们还提出了一种对NET患者进行分层的算法,以接受或不接受PRRT联合疗法。考虑到PRRT和许多这类联合用药已经用于治疗NET和其他癌症的患者,
更新日期:2020-03-19
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