| Objective:It is proposed to use new molecular probes 68Ga-NOTA-NT/ICG-NT and 68Ga-NOTA-RM26（GRP）/ICG-RM26 to explore the feasibility of PET imaging and optical imaging in the diagnosis and intraoperative navigation of pancreatic cancer.Method:Two human pancreatic cancer cell lines panc-1 and SW1990 were cultured,and reverse transcription PCR（RT-PCR）and immunofluorescence were performed to detect the protein levels of NTR1and GRPR in the two cell lines.At the same time,the pan-1 subcutaneous transplanted tumor model was constructed in nude mice,and positron emission computed tomography（PET）imaging was performed on68Ga-NOTA-NT and 68Ga-NOTA-RM26 mall animals,and near-infrared fluorescence imaging was performed on ICG-NT and ICG-RM26,respectively,to verify the molecular imaging results histologically.Finally,statistical software Graphpad Prism 8.0 was used to analyze whether there were statistical differences among the data of each group.Results:RT-PCR results showed that the m RNA expression level of NTR1 in PANC-1 cell line was about 16 times higher than that in SW1990 cell line.The m RNA expression level of GRPR in PANC-1 cell line was much higher than that in SW1990 cell line,which was about 510times.Cell immunofluorescence showed that NTR1 and GRPR were mostly located in the cytoplasm,and the fluorescence intensity of PAN-1cell line was significantly stronger than that of SW1990 cell.In PET imaging of small animals,both 68GA-NOTA-NT and 68GA-NOTA-RM26molecular probes can accurately locate the tumor foci of the nude mouse PAN-1 subcutaneous transplanted tumor model.At the same time,the tumor had a high uptake value(the average uptake value of68Ga-NOTA-NT and 68GA-NOTA-RM26 was 0.21%ID/g and 0.30%ID/g respectively 1 hour after injection).In addition,the uptake value of normal tissues was low(the average uptake value of 68GA-NOTA-NT and68GA-NOTA-RM26 on the opposite side was 0.065%ID/g and0.070%ID/g).In the results of near-infrared fluorescence imaging,Both of the two tracers showed high fluorescence signal（the average value of ICG-NT was 6.119×108（p/s/cm2/sr）/（μW/cm2）and the average value of ICG-RM26 was 7.304×108（p/s/cm2/sr）/（μW/cm2）in the experimental group 24h after injection）.The mean ICG-NT background value was4.555×108（p/s/cm2/sr）/（μW/cm2）and the mean ICG-RM26 background value was 3.058×108（p/s/cm2/sr）/（μW/cm2）in the control group 24h after injection.Conclusion:1.NTR1 and GRPR can be used as targets for targeted imaging of pancreatic ductal adenocarcinoma2.PET/CT imaging with molecular probes 68Ga-NOTA-NT and68Ga-NOTA-RM26 can accurately image Panc-1 transplanted tumors with NTR1 and GRPR positivity3.The results of optical imaging and immunohistochemical detection of Panc-1 transplanted tumor confirmed the expression of NTR1 receptor and GRPR receptor in Panc-1 cells again,which provided an experimental basis for the integration of accurate diagnosis and treatment of pancreatic cancer in the future... |
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