| Summary: | 碩士 === 國立陽明大學 === 放射醫學科學研究所 === 95 === Objectives: 2-Deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) was generally considered a sensitive but not specific probe for tumor imaging. [18F]fluoromisonidazole ([18F]FMISO) was regarded as a hypoxia imaging agent. [18F]fluoroacetate ([18F]FAc) was proposed as a possible alternative to [11C]-acetate and is also applied as a tumor imaging agent. Accumulation of [18F]FDG in inflammatory lesion was well documented, while that of [18F]FMISO and [18F]FAc was not. This study compared the biodistribution of the three tracers in a sarcoma- and inflammatory lesion- bearing mouse model.
Methods: Radiosynthesis of [18F]FMISO and [18F]FAc were slightly modified from previous report. The decay-corrected radiochemical yields of [18F]FMISO and [18F]FAc were 20%~25% and 35%~40%, respectively. The radiochemical purity was greater than 90% for [18F]FMISO and 95% for [18F]FAc. C3H mice were inoculated with 2x105 KHT sarcoma cells in the right thigh on day 0. Turpentine oil (0.1mL ) was injected in the left thigh on day 11 to induce inflammatory lesion. Biodistribution, pharmacokinetics and microPET imaging of the three tracers were performed on day 14 after tumor inoculation.
Results: The inflammatory lesions was clearly visualized by [18F]FDG/microPET and autoradiography at 3 days after turpentine oil injection. Derived from microPET image, the tumor-to-muscle (Tu/Mu) and inflammatory lesion-to-muscle (Inf/Mu) ratios were 8.13 and 4.66 for [18F]FDG (n=3), 6.93 and 1.53 for [18F]FMISO (n=6), and 3.80 and 3.25 for [18F]FAc (n=6) at 4 hr post injection. Among these, the tumor-to-inflammatory lesion ratio was highest for [18F]FMISO (4.63) compared with that of [18F]FDG (1.75) and [18F]FAc (1.18). The distribution half-life (t1/2α) and the elimination half-life (t1/2β) were 0.09 hr and 1.08 hr for [18F]FMISO, 0.05 hr and 5.05 hr for [18F]FDG, and 0.15 hr and 11.33 hr for [18F]FAc in mice. The area under curve (AUC) is 11.78, 12.41 and 116.23 hr ´ %ID/g for [18F]FMISO, [18F]FDG and [18F]FAc, respectively. The AUC showed the highest bioavailability of [18F]FAc among these traces in mice.
Conclusions: MicroPET images showed that [18F]FDG and [18F]FAc delineated both tumor and inflammatory lesion while [18F]FMISO accumulated in tumor significantly higher than that in inflammatory lesion at 4 hr post injection. The uptake of [18F]FMISO in inflammatory lesions is lowest among these tracers. Our result demonstrated the potential of [18F]FMISO in distinguishing tumor from inflammatory lesion in a mouse model.
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