Imaging of tumor colonization by <i>Escherichia coli</i> using <sup>18</sup>F-FDS PET
Sae‐Ryung Kang, Eui Jeong Jo, Vu H. Nguyen, Ying Zhang, Hee Seung Yoon, Ayoung Pyo, Dong-Yeon Kim, Yeongjin Hong, Hee‐Seung Bom, Jung‐Joon Min
Abstract
Tumor-targeting bacteria have been actively investigated as a new therapeutic tool for solid tumors. However, in vivo imaging of tumor-targeting bacteria has not been fully established. 18 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 18 F-FDS PET for visualization of the colonization and proliferation of tumor-targeting Escherichia coli (E. coli) MG1655 in mouse tumor models. Methods: E. coli (5 10 7 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 18 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 (SUVmax). Results: 18 F-FDS uptake was significantly higher in tumors colonized by live E. coli MG1655 than in uncolonized tumors (p < 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 18 F-FDS uptake correlated very strongly with the number of E. coli in tumors (r = 0.823, p < 0.0001). Cross sectional analysis of autoradiography, bioluminescence, and pathology revealed that the 18 F-FDS uptake sites in tumors matched the locations of E. coli MG1655.