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Theranostics 2020; 10(11):4958-4966. doi:10.7150/thno.42121 This issue Cite

Research Paper

Imaging of tumor colonization by Escherichia coli using ¹⁸F-FDS PET

Sae-Ryung Kang^1,2, Eui Jeong Jo², Vu Hong Nguyen^1,3, Ying Zhang², Hee Seung Yoon², Ayoung Pyo², Dong-Yeon Kim^1,2, Yeongjin Hong⁴, Hee-Seung Bom^1,2, Jung-Joon Min^1,2✉

1. Department of Nuclear Medicine, Chonnam National University Medical School and Hwasun Hospital, Hwasun, Jeonnam, Korea
2. Institute for Molecular Imaging and Theranostics, Chonnam National University Medical School, Hwasun, Jeonnam, Korea
3. Department of Experimental Therapeutics, Beckman Research Institute of City of Hope, Duarte, CA 91010, USA
4. Department of Microbiology, Chonnam National University Medical School, Hwasun, Jeonnam, Korea

✉ Corresponding author: Jung-Joon Min, Department of Nuclear Medicine, Chonnam National University Hwasun Hospital, 264 Seoyang-ro, Hwasun, Jeonnam 58128, Republic of Korea. TEL: +82-61-379-2876, FAX: +82-61-379-2875, Email: jjminac.kr

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. ¹⁸F-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 ¹⁸F-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 × 10⁷ 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 ¹⁸F-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_max).

Results: ¹⁸F-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 ¹⁸F-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 ¹⁸F-FDS uptake sites in tumors matched the locations of E. coli MG1655.

Conclusion: In conclusion, ¹⁸F-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 E. coli.

Keywords: tumor-targeting bacteria, Escherichia coli, bacterial cancer therapy, ¹⁸F-fluorodeoxysorbitol (¹⁸F-FDS), positron emission tomography (PET)

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