TY - JOUR T1 - <strong>Multi-drug synergistic antitumor based on exosomes and monitoring its delivery with PET imaging</strong> JF - Journal of Nuclear Medicine JO - J Nucl Med SP - 1062 LP - 1062 VL - 61 IS - supplement 1 AU - Ruijie Qian AU - Xiaoli Lan AU - Rui An Y1 - 2020/05/01 UR - http://jnm.snmjournals.org/content/61/supplement_1/1062.abstract N2 - 1062Objectives: Exosomes are a kind of natural nanoparticles targeting tumors, and exosomes have recently been used for drug delivery. This aim of this study was to use exosomes to encapsulate multiple drugs to synergistically suppress tumors, and to monitor drug delivery of exosomes under the guidance of nuclide PET imaging. Methods: Exosomes (TEX @ DOX @ ALA) was obtained by the directing incubation method and hypotonic pre-expansion method to load the doxorubicin (DOX) and 5-aminoketovaleric acid (ALA),and then it was examined by transmission electron microscopy (TEM), dynamic light scattering (DLS), and western blot analysis (WB); Flow apoptosis detection method and CCK8 assay was used to detect the ability of TEX @ DOX @ ALA to effectively kill tumor cells; The TEX @ DOX @ ALA labelled by fluorescent dye CY5.5 was injected into the tumor-bearing nude mice through tail veins for near-infrared fluorescence (NIRF) imaging at different times(1, 12, 24,and 48h) to explore the biodistribution of TEX @ DOX @ ALA in vivo. According to the NIRF images, with exosomes labelled with N3, 68Ga-NETA-DBCO imaging was carried out with pre-targeting technology to determine the optimal pre-targeting time and imaging time,and the drug delivery ability of TEX @ DOX @ ALA was confirmed by confocal microscopy and flow cytometry. TEX @ DOX @ ALA was injected into colon cancer cell bearing models to monitor the tumor growth and survival. Orthotopic colon cancer models and liver metastases models were set up comprehensively evaluate the ability of TEX @ DOX @ ALA to trace tumors. Results: The drug-loaded exosomes, TEX @ DOX @ ALA, did not change significantly under TEM, DLS and WB. Flow cytometry and CCK8 assay proved that TEX @ DOX @ ALA can effectively inhibit tumor cell activity, with a minimum of 30.7%. The NIRF images showed that the tumor had clearest images at 24h after administration of TEX @ DOX @ ALA. And Confocal microscopy and flow cytometry showed that TEX @ DOX @ ALA could effectively deliver drugs. PET / CT images and the biodistribution results show that the optimal pre-targeting time is 24 hours. After injecting of 68Ga-NETA-DBCO, the images are getting better.When the % ID / g is 4 hours, the T / M is about 5.7. After TEX @ DOX @ ALA was injected into tumor-bearing mice, tumor growth was slower, the survival time of mice was significantly prolonged, and no important organs (liver, kidney, etc. ) were damaged. TEX @ DOX @ ALA can effectively trace orthotopic colon cancer and liver metastases. Conclusions: This research successfully developed an exosome multiple drug loading which could have significant anti-tumor results, and this results could be successfully monitored by PET nuclear imaging with 68Ga pretargeting technology. This study confirmed that exosomes may be excellent drug carriers that can effectively target tumors, and it may hold great potential in constructing multi-modality diagnosis and treatment integrated probe. Funding: This work was supported by the National Natural Science Foundation of China (No. 81873904) ER -