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Reproducibility of 3'-Deoxy-3'-¹⁸F-Fluorothymidine MicroPET Studies in Tumor Xenografts in Mice

¹ Molecular Imaging Program of Stanford, Bio-X Program, and Department of Radiology, Stanford University School of Medicine, Stanford, California
² Department of Radiology, University of California, Los Angeles, Los Angeles, California
³ Department of Pharmacy, University of Southern California, Los Angeles, California

3'-Deoxy-3'-¹⁸F-fluorothymidine (¹⁸F-FLT) has been used to image tumor proliferation in preclinical and clinical studies. Serial microPET studies may be useful for monitoring therapy response or for drug screening; however, the reproducibility of serial scans has not been determined. The purpose of this study was to determine the reproducibility of ¹⁸F-FLT microPET studies. Methods: C6 rat glioma xenografts were implanted into nude mice (n = 9) and grown to mean diameters of 5–17 mm for approximately 2 wk. A 10-min acquisition was performed on a microPET scanner approximately 1 h after ¹⁸F-FLT (1.9–7.4 MBq [50–200 µCi]) was injected via the tail vein. A second microPET scan was performed approximately 6 h later on the same day after reinjection of ¹⁸F-FLT to assess for reproducibility. Most of the mice were studied twice within the same week (for a total of 17 studies). Images were analyzed by drawing an ellipsoidal region of interest (ROI) around the tumor xenograft activity. Percentage injected dose per gram (%ID/g) values were calculated from the mean activity in the ROIs. Coefficients of variation and differences in %ID/g values between studies from the same day were calculated to determine the reproducibility after subtraction of the estimated residual tumor activity from the first ¹⁸F-FLT injection. Results: The coefficient of variation (mean ± SD) for %ID/g values between ¹⁸F-FLT microPET scans performed 6 h apart on the same day was 14% ± 10%. The difference in %ID/g values between scans was –0.06% ± 1.3%. Serum thymidine levels were mildly correlated with %ID/g values (R² = 0.40). Tumor size, mouse body weight, injected dose, and fasting state did not contribute to the variability of the scans; however, consistent scanning parameters were necessary to ensure accurate studies, in particular, controlling body temperature, the time of imaging after injection, and the ROI size. Conclusion: ¹⁸F-FLT microPET mouse tumor xenograft studies are reproducible with moderately low variability. Serial studies may be performed to assess for significant changes in therapy response or for preclinical drug development.

Key Words: ¹⁸F-FLT • microPET • reproducibility • tumor xenograft • drug development

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