RT Journal Article
SR Electronic
T1 Gene Expression Patterns and Tumor Uptake of <sup>18</sup>F-FDG, <sup>18</sup>F-FLT, and <sup>18</sup>F-FEC in PET/MRI of an Orthotopic Mouse Xenotransplantation Model of Pancreatic Cancer
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 1362
OP 1370
DO 10.2967/jnumed.107.050021
VO 49
IS 8
A1 Corinna von Forstner
A1 Jan-Hendrik Egberts
A1 Ole Ammerpohl
A1 Dagmara Niedzielska
A1 Ralph Buchert
A1 Pal Mikecz
A1 Udo Schumacher
A1 Kersten Peldschus
A1 Gerhard Adam
A1 Christian Pilarsky
A1 Robert Grutzmann
A1 Holger Kalthoff
A1 Eberhard Henze
A1 Winfried Brenner
YR 2008
UL http://jnm.snmjournals.org/content/49/8/1362.abstract
AB Our aim was to use PET/MRI to evaluate and compare the uptake of 18F-FDG, 3-deoxy-3-18F-fluorothymidine (18F-FLT), and 18F-fluorethylcholine (18F-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 (PancTuI, 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: 18F-FLT showed the highest tumor uptake, with a mean TLR of 2.3, allowing correct visualization of all 12 pancreatic tumors. 18F-FDG detected only 4 of 8 tumors and had low uptake in tumors, with a mean TLR of 1.1 in visible tumors. 18F-FEC did not show any tumor uptake. Gene array analysis revealed that both hexokinase 1 as the rate-limiting enzyme for 18F-FDG trapping and pancreas-specific glucose transporter 2 were significantly downregulated whereas thymidine kinase 1, responsible for 18F-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 18F-FEC were predominantly unaffected or downregulated in the tumor cell lines. Conclusion: In comparison to 18F-FDG and 18F-FEC, 18F-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.