Adant Samuel, Shah Girish M, Beauregard Jean-Mathieu
Department of Radiology and Nuclear Medicine and Cancer Research Centre, Université Laval, Quebec City, QC, Canada.
Department of Medical Imaging and Oncology Division of Research Centre, CHU de Québec - Université Laval, 11, Côte du Palais, Quebec City, G1R 2J6, QC, Canada.
Eur J Nucl Med Mol Imaging. 2020 Apr;47(4):907-921. doi: 10.1007/s00259-019-04499-x. Epub 2019 Sep 6.
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 Lu-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.
神经内分泌肿瘤（NETs）的发病率正在上升，但由于诊断往往延迟到肿瘤发生转移，所以治愈性治疗选择有限。肽受体放射性核素治疗（PRRT）是转移性NETs最有效的治疗选择之一，因为它能通过生长抑素受体（SSTR）将放射性靶向递送至肿瘤，且全身毒性相对较低。然而，目前的PRRT方案只能缓解症状而非治愈疾病，更高剂量的PRRT虽可能实现缓解，但对患者的毒性也会过大。因此，有必要通过将PRRT与其他药物联合使用来改善NETs的治疗效果，从而在内部放射治疗中获得最大益处，同时使非靶器官免受辐射毒性影响。在此，我们综述了各种当前及潜在的联合策略，以改善基于镥 - 奥曲肽的NETs的PRRT，其中一些策略也可能适用于其他放射性核素治疗。这些策略包括共同给药的药物，它们可通过增加肿瘤灌注或提高肿瘤表面的SSTR密度来改善放射性药物的递送。其他联合策略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，以有效提高PRRT的细胞毒性。我们还提出了一种算法，用于对NET患者进行分层，以确定是否接受PRRT联合治疗。鉴于PRRT和许多这些联合药物已用于治疗NET和其他癌症患者，所提出的提高PRRT疗效的策略可迅速转化应用于临床。
