TY - JOUR T1 - Evaluation of bacteria Nissle 1917 for tumor targeting imaging JF - Journal of Nuclear Medicine JO - J Nucl Med SP - 444 LP - 444 VL - 61 IS - supplement 1 AU - Qingyao Liu AU - Xiali Lan Y1 - 2020/05/01 UR - http://jnm.snmjournals.org/content/61/supplement_1/444.abstract N2 - 444Objectives: The diagnosis efficiency of tumor remains low,as most of the administrated traces are uptaken by reticuloendothelial system (RES) before reaching the target tumor site. It is necessary to explore more advanced systems for diagnosis of tumor with high specificity and efficacy. Bacteria Escherichia coli Nissle 1917 (EcN) is used as the probiotic for clinical treatment of various intestinal diseases such as diarrhea. It has been reported that EcN prefers to accumulate and selectively replicatein tumor tissues by virtue of its preference for hypoxia and nutrients. Moreover, the large genome of EcN allows it to be genetically modified and carry exogenous genes to deliver therapeutic proteins and cytokines. In this study, we introduced human somatostatin receptors subtype-2 (hSSTR2) into EcN genome. When the EcN colonize, replicate and overexpress the hSSTR2 in the tumor site, we evaluate binding characters using 68Ga-DOTA-TATE for the tumor imaging. Methods: Recombinant DNA donor fragments were constructed with homologous arms-Ptac promoter-hSSTR2-cm+ resistant cassette, and thenintegrated into EcN genome by CRISPR. The expression of hSSTR2 in the resulting EcN-hSSTR2clone was investigated by PCR. The binding assay with 68Ga- DOTA-TATE was performedin vitro. EcN-hSSTR2was injected in vein on the mice bearing H22 xenograft model, and the biodistribution of EcN was determined by counting bacteria. hSSTR2 expression in tissues was determined by western-blot. At different time points post-injection of EcN-hSSTR2,PET imaging and biodistribution study using68Ga-DOTA-TATE were performed. Results: We have successfullyintegrated hSSTR2 into EcN genome by CRISPR, and the sequence of hSSTR2 expressed in those clones was confirmed by PCR. hSSTR2 expressed from EcN-hSSTR2showed high affinity and specificity with 68Ga-DOTA-TATE. In vivo study showed that the number of EcN-hSSTR2 in tumor site remained at nearly 4000 times higher than liver 8 days post-administration, which demonstrated the superiortumor-specific colonization and replication ability.The same trend happened in hSSTR2 expression that the expression in tumor is much higher than other tissues. MicroPET images showed high uptake of 68Ga-DOTA-TATE in H22 tumor. Conclusions: We have successfully constructed an engineering bacteria Nissle 1917 superior targeting the tumor and overexpressing the hSSTR2, and 68Ga-DOTA-TATE could binding the hSSTR2 for PET imaging. It provides a feasible and efficient strategy to realize the bacteria-driven tumor detection, making it practical for clinical use. Acknowledgement: This work was supported by the National Natural Science Foundation of China (No.81501532 and 81630049). ER -