Ranieri Girolamo, Marech Ilaria, Niccoli Asabella Artor, Di Palo Alessandra, Porcelli Mariangela, Lavelli Valentina, Rubini Giuseppe, Ferrari Cristina, Gadaleta Cosmo Damiano
Interventional Radiology Unit with Integrated Section of Medical Oncology, National Cancer Research Centre, Istituto Tumori "Giovanni Paolo II", Bary 70124, Italy.
Nuclear Medicine Unit, University of Bari "Aldo Moro", Bari 70124, Italy.
Int J Mol Sci. 2017 Sep 9;18(9):1937. doi: 10.3390/ijms18091937.
Renal cell carcinoma (RCC) is the most frequent renal tumor and the majority of patients are diagnosed with advanced disease. Tumor angiogenesis plays a crucial role in the development and progression of RCC together with hypoxia and glucose metabolism. These three pathways are strictly connected to the cell growth and proliferation, like a loop that is self-feeding. Over the last few years, the ever-deeper knowledge of its contribution in metastatic RCC led to the discovery of numerous tyrosine kinase inhibitors (TKIs) targeting pro-angiogenic receptors at different levels such as sunitinib, sorafenib, pazopanib, axitinib, tivozanib, and dovitinib. As anti-angiogenic agents, TKIs interfere the loop, being able to inhibit tumor proliferation. TKIs are now available treatments for advanced RCC, which demonstrated to improve overall survival and/or progression free survival. Their effects can be detectable early on Positron Emission Tomography/Computed Tomography (PET/CT) by change in F-fluoro-2-deoxy-2-d-glucose (F-FDG) uptake, the main radiotracer used to date, as a strong indicator of biological response. F-FDG PET/CT demonstrated an ability to predict and monitor disease progression, allowing an early and reliable identification of responders, and could be used for image-guided optimization and "personalization" of anti-angiogenic regimens. New radiotracers for biometabolic imaging are currently under investigation, which exploit the other pathways involved in the cancer process, including cellular proliferation, aerobic metabolism, cell membrane synthesis, hypoxia and amino acid transport, as well as the angiogenic process, but they require further studies.
肾细胞癌（RCC）是最常见的肾脏肿瘤，大多数患者被诊断为晚期疾病。肿瘤血管生成与缺氧和葡萄糖代谢一起在RCC的发生和发展中起着关键作用。这三条途径与细胞生长和增殖密切相关，就像一个自我反馈的循环。在过去几年中，对其在转移性RCC中作用的深入了解导致发现了许多靶向不同水平促血管生成受体的酪氨酸激酶抑制剂（TKIs），如舒尼替尼、索拉非尼、帕唑帕尼、阿昔替尼、替沃扎尼和多韦替尼。作为抗血管生成药物，TKIs干扰这个循环，能够抑制肿瘤增殖。TKIs现在是晚期RCC的可用治疗方法，已证明可改善总生存期和/或无进展生存期。它们的效果可以通过正电子发射断层扫描/计算机断层扫描（PET/CT）上F-氟-2-脱氧-D-葡萄糖（F-FDG）摄取的变化早期检测到，F-FDG是迄今为止使用的主要放射性示踪剂，是生物反应的有力指标。F-FDG PET/CT显示出预测和监测疾病进展的能力，能够早期可靠地识别反应者，可用于抗血管生成方案的图像引导优化和“个性化”。目前正在研究用于生物代谢成像的新放射性示踪剂，它们利用癌症过程中涉及的其他途径，包括细胞增殖、有氧代谢、细胞膜合成、缺氧和氨基酸转运以及血管生成过程，但它们还需要进一步研究。
