RT Journal Article
SR Electronic
T1 Visualization of the migration of bone marrow derived dendritic cells and its antitumor effects with multimodal optical reporter gene imaging
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 89
OP 89
VO 57
IS supplement 2
A1 Subi Ahn
A1 Thoudam Debraj Singh
A1 Sang Bong Lee
A1 Seul-Gi Oh
A1 Seung Yun Yoon
A1 Shin Young Jeong
A1 Sang-Woo Lee
A1 Byoeng-Cheol Ahn
A1 Jaetae Lee
A1 Yong Hyun Jeon
YR 2016
UL http://jnm.snmjournals.org/content/57/supplement_2/89.abstract
AB 89Objectives Herein, we sought to monitor the migration of bone marrow-derived dendritic cells (BMDCs) by the use of dual reporter genes of sodium iodide symporter (NIS) and enhanced firefly luciferase (effluc) in living mice and evaluate the antitumor effects by immunization of BMDCs expressing the dual reporter genes. Methods BMDCs were transduced with retrovirus co-expressing hNIS, effluc and thy1.1 genes, named as BMDC/NF. Iodide uptake and luciferase assay were done to evaluate the gene expression level of respective reporters in BMDC/NF. To examine the effect of viral infection on BMDC function, cell proliferation, levels of antigen uptake, phenotype expression, and migration ability were evaluated. Furthermore, in vivo antitumor effects by pre-vaccination of BMDC/NF cells pulsed with cervical cancer cells TC-1 lysate was serially monitored by bioluminescent imaging (BLI). For the DC tracking study, either BMDC or BMDC/NF cells were subcutaneously administered into left and right footpad of mice, respectively, and their migration to draining popliteal lymph nodes (DPLNs) was monitored with combined I-124 PET/CT and BLI. Results Iodide uptake and luciferase activity were about 5- and 10-fold higher in BMDC/NF cells than BMDCs, respectively. There were no significant differences in cell proliferation, levels of antigen uptake and phenotype expression, and migration ability between BMDC and BMDC/NF cells. Interestingly, in vivo BLI revealed the successful tumor protection in mice immunized with TC-1 lysate-pulsed BMDC/NF cells until 2 weeks post-tumor challenge. More interestingly, BLI signal was clearly detected in DPLNs of the BMDC/NF injection site at day 7 post-injection. Consistently, I-124 PET/CT imaging showed the higher radioactivity in DPLNs of BMDC/NF injection site than BMDC injection site. Conclusions We successfully tracked the migration of BMDCs to the lymphoid organ in living mice with optical and PET imaging techniques by tagging of NIS and effluc reporter genes to the cells, without alteration of biological function as well as generation of antitumor immunity.