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Hypoxia-Specific Tumor Imaging with ¹⁸F-Fluoroazomycin Arabinoside

¹ Nuclear Medicine Clinic, Technical University of Munich, Munich, Germany
² Radiopharmacy, PET Center, University of Tuebingen, Tuebingen, Germany
³ Department of Nuclear Medicine, Institute H. San Raffaele, Milan, Italy
⁴ Cross Cancer Institute and University of Alberta, Edmonton, Alberta, Canada

View larger version (8K): [in a new window]   FIGURE 1. Chemical structure of 18F-fluoroazomycin arabinoside (18F-FAZA). Nucleoside analog contains nitroimidazole ring in -position of arabinose ring.

View larger version (28K): [in a new window]   FIGURE 2. Typical serial transaxial small animal 18F-FAZA PET scans of 2 Swiss nude mice bearing subcutaneous A431 tumors at right side of thorax. Note decreased tracer uptake after breathing 100% O2 for 8 h. ROI analyses, as shown in experiment 1 (Exp. 1), revealed that the mean T/Bk ratio decreased from 4.7:1 (breathing room air) to 3.7:1 (breathing 100% O2) in experiment 1 and from 11.3:1 to 5.4:1 in experiment 2 (Exp. 2), respectively.

View larger version (16K): [in a new window]   FIGURE 3. T/Bk ratio of 18F-FAZA (y-axis) in 13 Swiss nude mice bearing A431 tumor using serial MADPET studies with and without oxygen breathing. Animals breathing oxygen on the first day are displayed with open symbols, whereas animals breathing room air on the first day are shown with filled symbols.

View larger version (16K): [in a new window]   FIGURE 4. Relationship of T/M ratio derived from biodistribution studies and T/Bk ratio of small animal PET studies. PET measurements were performed 150–180 min after injection of 10 MBq 18F-FAZA into Swiss nude mice bearing A431 tumor. During scanning, animals breathed either room air (circles) or 100% oxygen (squares). Regression analysis revealed a significant linear correlation between both measurements (regression line y = 0.89 + 0.75x; adjusted r2 = 0.57; P < 0.01; dotted lines, 95% confidence intervals).

View larger version (48K): [in a new window]   FIGURE 5. Digital autoradiographic image of radioactivity 3 h after 18F-FAZA administration (20-µm slice thickness).