Department of Nuclear Medicine, Changzhou Second People's Hospital, Nanjing Medical University, Changzhou, China.
Department of Nuclear Medicine, First Affiliated Hospital, Soochow University, Suzhou, China.
Cancer Biother Radiopharm. 2018 Dec;33(10):445-459. doi: 10.1089/cbr.2017.2395. Epub 2018 Aug 22.
To study the distribution and imaging of Tc-nGO-PEG-FA in human pancreatic cancer Patu8988 tumor-bearing nude mice, and to explore its usefulness as an imaging reagent for pancreatic cancer. Natural graphite powder was used as raw material to prepare the nanosized graphene oxide (nGO) by using the modified Hummers method, and then was covalently modified by polyethylene glycol (PEG) on the surface of nGO. The nGO was further optimized by cell experiment, and then conjugated with the targeting molecule folic acid (FA) to form nGO-PEG-FA system. The nGO-PEG-FA was finally labeled by radioactive nuclide Tc by direct labeling method to form the Tc-nGO-PEG-FA molecular imaging probe. Nude mice bearing patu8988 pancreatic cancer xenografts were intravenous injection (I.V.) injected with Tc-nGO-PEG-FA, and the distribution of Tc-nGO-PEG-FA in nude mice at different time course was investigated by determination of tissue uptake of radioactivity (%ID/g), as well as the single photon emission computed tomography (SPECT) imaging at different time course. The labeling rate of nGO-PEG-FA with Tc was (90.08 ± 2.34)%, and the highest binding rate of Tc-nGO-PEG-FA with Patu8988 cells was (3.15 ± 0.31)%. The radioactive uptake in tumor reached (5.11 ± 1.23)%ID/g at 6 h after I.V. injection of Tc-nGO-PEG-FA in nude mice. Meanwhile, the radioactive uptake in liver, spleen, and lung was also high and reached (10.33 ± 1.22)%ID/g, (5.86 ± 0.59)%ID/g, and (3.55 ± 0.93)%ID/g, respectively, whereas less radioactivity uptake was observed in the heart (1.12 ± 0.33)%ID/g and blood (2.76 ± 0.39)%ID/g, respectively. The tumors can be clearly imaged at 4.0-6.0 h after Tc-nGO-PEG-FA injection. Tc-nGO-PEG-FA can efficiently target pancreatic cancer, which may be developed as an imaging agent for pancreatic cancer.
为了研究 Tc-nGO-PEG-FA 在人胰腺癌细胞 Patu8988 荷瘤裸鼠中的分布和成像，并探讨其作为胰腺癌成像试剂的用途。 以天然石墨粉为原料，采用改进的 Hummers 法制备纳米氧化石墨烯（nGO），然后在 nGO 表面通过聚乙二醇（PEG）进行共价修饰。通过细胞实验对 nGO 进行进一步优化，然后与靶向分子叶酸（FA）偶联形成 nGO-PEG-FA 系统。最后，nGO-PEG-FA 通过直接标记法被放射性核素 Tc 标记，形成 Tc-nGO-PEG-FA 分子成像探针。荷 Patu8988 胰腺癌细胞的裸鼠静脉注射（I.V.） Tc-nGO-PEG-FA，通过放射性摄取组织（%ID/g）测定和不同时间点的单光子发射计算机断层扫描（SPECT）成像，研究 Tc-nGO-PEG-FA 在裸鼠体内的分布。nGO-PEG-FA 的 Tc 标记率为（90.08±2.34）%，Tc-nGO-PEG-FA 与 Patu8988 细胞的最高结合率为（3.15±0.31）%。荷瘤裸鼠静脉注射 Tc-nGO-PEG-FA 后 6h，肿瘤放射性摄取达到（5.11±1.23）%ID/g。同时，肝、脾、肺放射性摄取也较高，分别达到（10.33±1.22）%ID/g、（5.86±0.59）%ID/g和（3.55±0.93）%ID/g，而心脏（1.12±0.33）%ID/g和血液（2.76±0.39）%ID/g的放射性摄取较少。Tc-nGO-PEG-FA 注射后 4.0-6.0h 可清晰显示肿瘤。Tc-nGO-PEG-FA 可有效靶向胰腺癌，有望开发为胰腺癌成像剂。
