Department of Nuclear Medicine, Chonnam National University Medical School and Hwasun Hospital, Hwasun, Jeonnam, Korea.
Institute for Molecular Imaging and Theranostics, Chonnam National University Medical School, Hwasun, Jeonnam, Korea.
Theranostics. 2020 Apr 1;10(11):4958-4966. doi: 10.7150/thno.42121. eCollection 2020.
Tumor-targeting bacteria have been actively investigated as a new therapeutic tool for solid tumors. However, imaging of tumor-targeting bacteria has not been fully established. F-fluorodeoxysorbitol (FDS) positron emission tomography (PET) is known to be capable of imaging Gram-negative Enterobacteriaceae infection. In the present study, we aimed to validate the use of F-FDS PET for visualization of the colonization and proliferation of tumor-targeting () MG1655 in mouse tumor models. (5 × 10 colony forming unit) were injected intravenously into BALB/c mice bearing mouse colon cancer (CT26). Before and 1, 3, and 5 days after the bacterial injection, PET imaging was performed following i.v. injection of approximately 7.4 MBq of F-FDS. Regions of interest were drawn in the engrafted tumor and normal organs including the heart, liver, lung, brain, muscle, and intestine. Semiquantitative analysis was performed using maximum standardized uptake value (SUV). F-FDS uptake was significantly higher in tumors colonized by live MG1655 than in uncolonized tumors ( < 0.001). The PET signals in the colonized tumors at 3 days after bacterial injection were 3.1-fold higher than those in the uncolonized tumors. Tumoral F-FDS uptake correlated very strongly with the number of in tumors (r = 0.823, < 0.0001). Cross sectional analysis of autoradiography, bioluminescence, and pathology revealed that the F-FDS uptake sites in tumors matched the locations of MG1655. In conclusion, F-FDS PET is expected to be useful for the semiquantitative visualization of tumor-targeting bacteria when bacterial cancer therapy is performed using Gram-negative Enterobacteriaceae such as .
肿瘤靶向细菌一直被积极研究作为治疗实体瘤的新工具。然而，肿瘤靶向细菌的成像尚未完全建立。F-氟代脱氧苏糖醇（FDS）正电子发射断层扫描（PET）已知能够成像革兰氏阴性肠杆菌科感染。在本研究中，我们旨在验证 F-FDS PET 用于可视化肿瘤靶向 () MG1655 在小鼠肿瘤模型中的定植和增殖的用途。（5×10 个菌落形成单位）静脉内注射到携带小鼠结肠癌（CT26）的 BALB/c 小鼠中。在细菌注射前和注射后 1、3 和 5 天，通过静脉内注射约 7.4 MBq 的 F-FDS 进行 PET 成像。在移植瘤和包括心脏、肝脏、肺、脑、肌肉和肠在内的正常器官中绘制感兴趣区域。使用最大标准化摄取值（SUV）进行半定量分析。与未定植肿瘤相比，活 MG1655 定植的肿瘤中 F-FDS 摄取显著更高（<0.001）。细菌注射后 3 天，定植肿瘤的 PET 信号比未定植肿瘤高 3.1 倍。肿瘤中的 F-FDS 摄取与肿瘤中 MG1655 的数量非常强相关（r = 0.823，<0.0001）。放射性自显影、生物发光和病理学的横截面分析表明，肿瘤中 F-FDS 摄取部位与 MG1655 的位置相匹配。总之，当使用革兰氏阴性肠杆菌科（如）进行细菌癌症治疗时，F-FDS PET 有望用于肿瘤靶向细菌的半定量可视化。
