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DOI: 10.1055/s-0034-1372809
Characterization of precursor lesions and tumor heterogeneity in murine endogenous pancreatic adenocarcinoma by 18F-FDG PET
Zielsetzung:
Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease due to a late and difficult diagnosis. Positron emission tomography (PET) with 18F-fluorodeoxyglucose (FDG) has been widely used for the diagnosis and staging of PDAC. Genetically engineered mouse models (GEMM) are well-established tools for preventive and preclinical studies in PDAC. A detailed characterization of these models via PET is lacking. Therefore, the goal of this study was to characterize the FDG tracer uptake in different GEMM of PDAC.
Material und Methodik:
Ptf1awt/Cre(C)Kraswt/LSL-G12D(K)Ela-Tgfa(T), CK;p53(P)wt/fl, CKPfl/fl, and CKTPwt/fl GEMM were generated. Tumors were confirmed by T2w MRI (Philips Achieva 1.5T). Consequently, animals were starved overnight and injected with 10 – 12 MBq of FDG through a tail vein catheter. Stationary PET scan was performed at 45 min post injection on a Siemens Inveon small-animal PET-CT system. Tissue samples were fixed with 4% PFA, dehydrated and cut into consecutive slices. Using Siemens IRW T2w images were fused with filtered back projection (FBP)-reconstructed PET data and correlated with respective histology. As quantitative values tumor to muscle ratios (T/M) were calculated for each ROI analyzed.
Ergebnisse:
Increased tracer uptake was observed in murine PDAC (T/M = 4.42 ± 1.9, p < 0.0001, ANOVA) compared to preneoplastic lesions (T/M=1.41±0.47), fibrotic pancreas (T/M=1.43±0.06) and IPMNs (T/M=2.29±1.08). No correlation was noted between tumor FDG uptake and genotype or grading (G1-G4). However, based on tissue composition two distinct groups could be identified differing in tumor cell and stromal content (T/M=3.5±1.79 versus 4.82±1.79) with a good correlation between tumor cell and T/M ratio (r2=0.66). Results were correlated with the glucose transporter GLUT2 expression in the respective samples.
Schlussfolgerungen:
FDG PET differentiates tumor cell and stroma rich regions in murine PDAC. Segmentation of FDG PET data may hold potential for characterization and response evaluation in human studies.
E-Mail: irina.heid@gmx.de