Department of Nuclear Medicine, La Timone University Hospital, CERIMED, Aix-Marseille University, Marseille, France.
Section on Medical Neuroendocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, USA.
Endocr Relat Cancer. 2019 Nov;26(11):R627-R652. doi: 10.1530/ERC-19-0165.
In recent years, advancement in genetics has profoundly helped to gain a more comprehensive molecular, pathogenic, and prognostic picture of pheochromocytomas and paragangliomas (PPGLs). Newly discovered molecular targets, particularly those that target cell membranes or signaling pathways have helped move nuclear medicine in the forefront of PPGL precision medicine. This is mainly based on the introduction and increasing experience of various PET radiopharmaceuticals across PPGL genotypes quickly followed by implementation of novel radiotherapies and revised imaging algorithms. Particularly, 68Ga-labeled-SSAs have shown excellent results in the diagnosis and staging of PPGLs and in selecting patients for PRRT as a potential alternative to 123/131I-MIBG theranostics. PRRT using 90Y/177Lu-DOTA-SSAs has shown promise for treatment of PPGLs with improvement of clinical symptoms and/or disease control. However, more well-designed prospective studies are required to confirm these findings, in order to fully exploit PRRT's antitumoral properties to obtain the final FDA approval. Such an approval has recently been obtained for high-specific-activity 131I-MIBG for inoperable/metastatic PPGL. The increasing experience and encouraging preliminary results of these radiotherapeutic approaches in PPGLs now raises an important question of how to further integrate them into PPGL management (e.g. monotherapy or in combination with other systemic therapies), carefully taking into account the PPGLs locations, genotypes, and growth rate. Thus, targeted radionuclide therapy (TRT) should preferably be performed at specialized centers with an experienced interdisciplinary team. Future perspectives include the introduction of dosimetry and biomarkers for therapeutic responses for more individualized treatment plans, α-emitting isotopes, and the combination of TRT with other systemic therapies.
近年来，遗传学的进步极大地帮助我们更全面地了解嗜铬细胞瘤和副神经节瘤（PPGLs）的分子、发病机制和预后情况。新发现的分子靶点，特别是那些针对细胞膜或信号通路的靶点，已经帮助核医学在 PPGL 精准医学中处于领先地位。这主要是基于各种 PET 放射性药物在 PPGL 基因型中的引入和不断增加的经验，随后迅速实施了新的放射疗法和修订的成像算法。特别是，68Ga 标记的 SSA 在 PPGL 的诊断和分期以及选择患者进行 PRRT 方面显示出了优异的结果，作为 123/131I-MIBG 治疗的潜在替代方法。使用 90Y/177Lu-DOTA-SSAs 的 PRRT 已显示出治疗 PPGL 的潜力，可以改善临床症状和/或疾病控制。然而，需要更多设计良好的前瞻性研究来证实这些发现，以便充分利用 PRRT 的抗肿瘤特性获得最终的 FDA 批准。最近，高比活度 131I-MIBG 获得了用于不可切除/转移性 PPGL 的批准。这些放射性治疗方法在 PPGL 中的经验不断增加和初步结果令人鼓舞，现在提出了一个重要问题，即如何将它们进一步整合到 PPGL 管理中（例如单药治疗或与其他全身治疗联合使用），同时仔细考虑 PPGL 的位置、基因型和生长速度。因此，靶向放射性核素治疗（TRT）最好在具有经验丰富的跨学科团队的专业中心进行。未来的展望包括引入治疗反应的剂量学和生物标志物，以制定更个体化的治疗计划，α 发射同位素，以及将 TRT 与其他全身治疗相结合。
