Bison Sander M, Konijnenberg Mark W, Melis Marleen, Pool Stefan E, Bernsen Monique R, Teunissen Jaap J M, Kwekkeboom Dik J, de Jong Marion
Department of Nuclear Medicine, Erasmus MC, Rotterdam, The Netherlands ; Department of Radiology, Erasmus MC, Rotterdam, The Netherlands ; Department of Medical Informatics, Erasmus MC, Rotterdam, The Netherlands.
Department of Nuclear Medicine, Erasmus MC, Rotterdam, The Netherlands.
Clin Transl Imaging. 2014;2(1):55-66. doi: 10.1007/s40336-014-0054-2. Epub 2014 Mar 5.
Peptide receptor radionuclide therapy (PRRT) has been shown to be an effective treatment for neuroendocrine tumors (NETs) if curative surgery is not an option. A majority of NETs abundantly express somatostatin receptors. Consequently, following administration of somatostatin (SST) analogs labeled with γ-emitting radionuclides, these tumors can be imaged for diagnosis, staging or follow-up purposes. Furthermore, when β-emitting radionuclides are used, radiolabeled peptides (radiopeptides) can also be used for the treatment for NET patients. Even though excellent results have been achieved with PRRT, complete responses are still rare, which means that there is room for improvement. In this review, we highlight some of the directions currently under investigation in pilot clinical studies or in preclinical development to achieve this goal. Although randomized clinical trials are still lacking, early studies have shown that tumor response might be improved by application of other radionuclides, such as α-emitters or radionuclide combinations, or by adjustment of radiopeptide administration routes. Individualized dosimetry and better insight into tumor and normal organ radiation doses may allow adjustment of the amount of administered activity per cycle or the number of treatment cycles, resulting in more personalized treatment schedules. Other options include the application of novel (radiolabeled) SST analogs with improved tumor uptake and radionuclide retention time, or a combination of PRRT with other systemic therapies, such as chemotherapy or treatment with radio sensitizers. Though promising directions appear to bring improvements of PRRT within reach, additional research (including randomized clinical trials) is needed to achieve such improvements.
如果无法进行根治性手术，肽受体放射性核素治疗（PRRT）已被证明是治疗神经内分泌肿瘤（NETs）的有效方法。大多数NETs大量表达生长抑素受体。因此，在给予标记有γ发射放射性核素的生长抑素（SST）类似物后，这些肿瘤可用于成像以进行诊断、分期或随访。此外，当使用发射β射线的放射性核素时，放射性标记的肽（放射性肽）也可用于治疗NET患者。尽管PRRT已取得了优异的效果，但完全缓解仍然很少见，这意味着仍有改进的空间。在这篇综述中，我们重点介绍了目前在试点临床研究或临床前开发中为实现这一目标而正在研究的一些方向。尽管仍缺乏随机临床试验，但早期研究表明，应用其他放射性核素，如α发射体或放射性核素组合，或调整放射性肽给药途径，可能会改善肿瘤反应。个体化剂量测定以及对肿瘤和正常器官辐射剂量的更好了解，可能允许调整每个周期的给药活度或治疗周期数，从而制定更个性化的治疗方案。其他选择包括应用具有改善的肿瘤摄取和放射性核素保留时间的新型（放射性标记的）SST类似物，或PRRT与其他全身治疗方法的联合应用，如化疗或使用放射增敏剂。尽管这些有前景的方向似乎使PRRT的改进触手可及，但仍需要更多的研究（包括随机临床试验）来实现这些改进。
