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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

¹ Department of Nuclear Medicine, University Hospital of Schleswig-Holstein, Campus Kiel, Kiel, Germany; ² Department of General Surgery and Thoracic Surgery, University Hospital of Schleswig-Holstein, Campus Kiel, Kiel, Germany; ³ Department of Nuclear Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; ⁴ Department of Anatomy II Experimental Morphology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; ⁵ Department of Diagnostic and Interventional Radiology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; and ⁶ Department of Visceral, Thoracic, and Vascular Surgery, University Hospital Carl Gustav Carus, Technical University of Dresden, Dresden, Germany

Correspondence: For correspondence or reprints contact: Winfried Brenner, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany. E-mail: winbren_2000{at}yahoo.com

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.

Key Words: pancreatic carcinoma • ¹⁸F-fluorodeoxyglucose • ¹⁸F-fluorothymidine • ¹⁸F-fluorethylcholine • MRI • PET • SCID mice • orthotopic xenotransplantation model • gene array

^* Contributed equally to this work.

COPYRIGHT © 2008 by the Society of Nuclear Medicine, Inc.

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