Meng Qingqing, Li Zheng, Li Shaoshun
School of Pharmacy, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai, China.
Curr Med Chem. 2016;23(41):4625-4638. doi: 10.2174/0929867323666161101100417.
Multidrug resistance (MDR) describes the resistance of tumor cells to chemotherapy and has been ascribed to the overexpression of drug efflux pumps. Molecular imaging of drug efflux pumps is helpful to identify the patients who may be resistant to the chemotherapy and thus will avoid the unnecessary treatment and increase the therapeutic effectiveness. Imaging probes targeting drug efflux pumps can non-invasively evaluate the Pgp function and play an important role in identification of MDR, prediction of response, and monitoring MDR modulation. On the other hand, new anticancer agents based on molecular targets such as epidermal growth factor receptor (EGFR) and angiogenic factor receptor may potentially be combined with chemotherapeutic drugs to overcome the MDR. Imaging of molecular targets visualize treatment response of patients at molecular level vividly and help to select right patients for certain targeted anticancer therapy. Among all the imaging modalities, nuclear imaging including positron emission tomography (PET) and single photon emission computed tomography (SPECT) imaging has the greatest promise for rapid translation to the clinic and can realize quantitative visualization of biochemical processes in vivo. In this review, we will summarize the nuclear imaging probes utilized for predicting and evaluating the early anticancer therapy response.99mTc labeled agents and PET based radiopharmaceuticals like 18F-Paclitaxel, 11C-Verapamil for drug efflux pumps imaging will be discussed here. Moreover, molecular imaging probes used for targeted therapy response evaluation like 18F-Tamoxifen,89Zr-Trastuzumab will also be introduced in this review.
多药耐药性(MDR)描述了肿瘤细胞对化疗的耐药性,这归因于药物外排泵的过度表达。药物外排泵的分子成像有助于识别可能对化疗耐药的患者,从而避免不必要的治疗并提高治疗效果。靶向药物外排泵的成像探针可以无创地评估Pgp功能,并在MDR的识别、反应预测和MDR调节监测中发挥重要作用。另一方面,基于表皮生长因子受体(EGFR)和血管生成因子受体等分子靶点的新型抗癌药物可能与化疗药物联合使用以克服MDR。分子靶点成像能够在分子水平生动地可视化患者的治疗反应,并有助于为特定的靶向抗癌治疗选择合适的患者。在所有成像方式中,包括正电子发射断层扫描(PET)和单光子发射计算机断层扫描(SPECT)成像在内的核成像在快速转化应用于临床方面最具前景,并且能够实现体内生化过程的定量可视化。在本综述中,我们将总结用于预测和评估早期抗癌治疗反应的核成像探针。本文将讨论用于药物外排泵成像的99mTc标记剂和基于PET的放射性药物,如18F-紫杉醇、11C-维拉帕米。此外,本综述还将介绍用于靶向治疗反应评估的分子成像探针,如18F-他莫昔芬、89Zr-曲妥珠单抗。