| [Objective] Positron Emission Tomography (PET) with specific tracers, such as 18F-2-Deoxy-2-Fluoro-D-Glucose(18F-FDG) and 18F-fluoromisonidazole(18F-MISO), can noninvasively visualize the glucose metabolism and hypoxia status of a tumor, whereas Mass Spectrometry Imaging(MSI) is a powerful tool to display the distribution of thousands of molecules in situ within a tissue section, with minimal sample preparation and holding advantages of easy manipulation, free of labeling. In this study, we underwent a multimodality imaging approach to combine PET-. Air Flow Assisted Ionization Mass Spectrometry Imaging(AFAI MSI) and Matrix Assisted Laser Desorption Ionization Mass Spectrometry Imaging(MALDI MSI) to localize and identify molecules related to glucose metabolism and hypoxia in a nude mouse model bearing breast tumor xenograft. The goal was to establish a new method for finding candidate molecules as tumor biomarkers.[Methods] Six-week-old nude mice (n=8) were injected subcutaneously with 2×106 4T1 breast tumor cells. After two weeks, the mice underwent ten-minute microPET scans using a Siemens Inveon system with 18F-FDG and 18F-FMISO as the tracers within consecutive two days. After that, all tumors were removed, marked and reserved in liquid nitrogen immediately. The tumors were cut into serial 8 mm-thick cryosections and analyzed by AFAI MSI and MALDI MSI respectively. The images were treated with dedicated software by referring the microPET images, and the most related molecules to the F-FDG and F-FMISO images were sorted out and analyzed.[Results]The molecules at m/z 744.4949,744.4996,770.5027,770.5126,771.5129, 771.5178,772.5248,798.5399,799.5469,799.5522,800.5499,813.5249,822.5476, 825.5591 in AFAI MSI were found most probably related to the 18F-FDG microPET images, and they were identified as phosphatidyl choline (PC) (30:0)/phosphatidyl ethanolamine (PE) (33:0), cardiolipin (CL) (72:7), PE(38:6)/PC(32:1), PC(32:1), PG(34:1), phosphatidylglycerol (PG) (36:4), PC(32:0), PC(34:1), PG(36:1)/PG(38:4), PG(38:4), PE(40:5)/PC(34:0), CL(84:15), PC(36:3), PG(40:5) respectively according to the analysis of the Human Metabolome Database (HMDB). The molecules at m/z 780.5510,788.6160,804.5531,830.5648,832.5769,832.5874 were found related to the 18F-FMISO microPET images. These molecules were identified as PC(34:2), PC(36:1), PC(38:7), PC(38:5), PC(38:4), PC(40:7). The molecules at m/z 501.28554, 525.28554,527.30119,792.55014,794.56816 in MALDI MSI were found most probably related to the 18F-FDG microPET images, and they were identified as PE(20:4),PE(22:6),PE(22:5),PC(37:5)/PE(40:5),PC(37:4)/PE(40:4)respectively according to the analysis of the Human Metabolome Database (HMDB). The molecules at m/z 419.25625,699.49864,701.51719,786.52627,788.54080,810.52827,812.54637, 834.52914 were found related to the 18F-FMISO microPET images. These molecules were identified as lysophosphatidic acid (LPA)(18:0), phosphatidic acid (PA) (36:2), PA(36:1),Phosphatidyl serines (PS) (36:2),PS(36:1),PS(38:4), PS(38:3), PS(40:6)。[Conclusions] A preliminarily method has been established to find out more molecules related to a specific molecular imaging pattern by combining analysis of the PET and MSI images of a tumor. This method holds a promise to seek new candidates as biomarkers of tumor and other diseases, as well. |
PDF Full Text Request