Gene expression patterns and tumor uptake of 18F-FDG, 18F-FLT, and 18F-FEC in PET/MRI of an orthotopic mouse xenotransplantation model of pancreatic cancer

Our aim was to use PET/MRI to evaluate and compare the uptake of F-18-FDG, 3-deoxy-3-F-18-fluorothymidine (F-18-FLT), and F-18-fluorethylcholine (F-18-FEC) in human pancreatic tumor cell lines after xenotransplantation into SCID mice and to correlate tumor uptake with gene expression of membrane transporters and rate-limiting enzymes for tracer uptake and tracer retention. Methods: Four weeks after orthotopic inoculation of human pancreatic carcinoma cells (PancTul, Colo357, and BxPC3) into SCID mice, combined imaging was performed with a small-animal PET scanner and a 3-T MRI scanner using a dedicated mouse coil. Tumor-to-liver uptake ratios (TLRs) of the tracers were compared with gene expression profiles of the tumor cell lines and both normal pancreatic tissue and pancreatic tumor tissue based on gene microarray analysis and quantitative polymerase chain reaction. Results: F-18-FLT showed the highest tumor uptake, with a mean TLR of 2.3, allowing correct visualization of all 12 pancreatic tumors. F-18-FDG detected only 4 of 8 tumors and had low uptake in tumors, with a mean TLR of 1.1 in visible tumors. F-18-FEC did not show any tumor uptake. Gene array analysis revealed that both hexokinase 1 as the rate-limiting enzyme for F-18-FDG trapping and pancreas-specific glucose transporter 2 were significantly downregulated whereas thymidine kinase 1, responsible for F-18-FLT trapping, was significantly upregulated in the tumor cell lines, compared with normal pancreatic duct cells and pancreatic tumor tissue. Relevant genes involved in the uptake of F-18-FEC were predominantly unaffected or downregulated in the tumor cell lines. Conclusion: In comparison to F-18-FDG and F-18-FEC. F-18-FLT was the PET tracer with the highest and most consistent uptake in various human pancreatic tumor cell lines in SCID mice. The imaging results could be explained by gene expression patterns of membrane transporters and enzymes for tracer uptake and retention as measured by gene array analysis and quantitative polymerase chain reaction in the respective cell lines. Thus, standard molecular-techniques provided the basis to help explain model-specific tracer uptake patterns in xenotransplanted human tumor cell lines in mice as observed by PET.