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Biologic Correlates of Intratumoral Heterogeneity in ¹⁸F-FDG Distribution with Regional Expression of Glucose Transporters and Hexokinase-II in Experimental Tumor

¹ Department of Nuclear Medicine, Graduate School of Medicine, Hokkaido University, Sapporo, Japan
² Department of Tracer Kinetics, Graduate School of Medicine, Hokkaido University, Sapporo, Japan
³ Department of Radiology, Nikko Memorial Hospital, Muroran, Japan
⁴ Department of Pathology, Hokkaido Gastroenterology Hospital, Sapporo, Japan

View larger version (98K): [in a new window]   FIGURE 1. ROIs were placed on ARG image, to cover mainly central (CT) and peripheral (PT) regions of viable tumor tissues and necrotic/apoptotic (NA) regions, with reference to corresponding sections stained with HE. SM = surrounding muscle.

View larger version (35K): [in a new window]   FIGURE 2. (A) Representative autoradiograph of 18F-FDG distribution. ARG image shows intratumoral heterogeneous 18F-FDG distribution. (B) Quantitative evaluation of intratumoral 18F-FDG distribution. 18F-FDG accumulation level in CT region was highest, which was 1.6 and 2.3 times higher than those in PT and NA regions, respectively (P < 0.001).

View larger version (104K): [in a new window]   FIGURE 3. Staining with anti-Glut-1 (A and D), anti-Glut-3 (B and E), and anti-HK-II (C and F) antibodies in CT region (top) was more prominent than those in PT region (bottom) in KDH-8 tumor tissues, respectively (x400).

View larger version (29K): [in a new window]   FIGURE 4. Expression levels of Glut-1, Glut-3, and HK-II were assessed by semiquantitative immunohistochemical grading performed by calculating the product of these scores (intensity x % positive). Histochemical scores of Glut-1, Glut-3, and HK-II were significantly higher in CT region than those in PT region (P < 0.001).

View larger version (134K): [in a new window]   FIGURE 5. Positive staining of HIF-1 was clearly observed in CT region (x400).

View larger version (15K): [in a new window]   FIGURE 6. Relationships between expression levels of Glut-1, Glut-3, and HK-II and intratumoral 18F-FDG accumulation in KDH-8 tumor tissues. Intratumoral 18F-FDG accumulation significantly correlated with expression levels of Glut-1, Glut-3, and HK-II (intensity x % positive). (A) Relationship between 18F-FDG accumulation and histochemical grading score for Glut-1. (B) Relationship between 18F-FDG accumulation and histochemical grading score for Glut-3. (C) Relationship between 18F-FDG accumulation and histochemical grading score for HK-II. , CT region; , PT region.