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Preclinical Evaluation of the Penciclovir Analog 9-(4-[¹⁸F]Fluoro-3-Hydroxymethylbutyl)Guanine for In Vivo Measurement of Suicide Gene Expression with PET

Department of Radiology, PET Imaging Science Center, University of Southern California, Los Angeles; and Gene Therapy Laboratory, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, California

View larger version (17K): [in a new window]   FIGURE 1. In vitro incorporation of [18F]FHBG into transduced (+) and nontransduced (-) cells at 1 and 5 h. Data are average of 3 experiments ± SEM; P < 0.001 for both time points (Student t test). cpm = counts per minute.

View larger version (26K): [in a new window]   FIGURE 2. HPLC radiochromatograms of [18F]FHBG (a) and its metabolites (b–d) in HT-29 tumor cells after 5-h incubation. (A) Transduced cells. (B) Nontransduced cells.

View larger version (15K): [in a new window]   FIGURE 3. Blood clearance curve of 18F activity in nude mice bearing transduced tumors after intravenous injection of [18F]FHBG (semilogarithmic plot; n = 3).

View larger version (17K): [in a new window]   FIGURE 4. Time–activity curve for arterial plasma from cynomolgus monkeys after intravenous injection of [18F]FHBG (semilogarithmic plot). Total plasma volume was estimated to be 2.5% of body weight in calculating %ID in plasma. Data are mean ± SEM from 2 monkeys. Error bars are smaller than symbols for most data points. Solid line is intended to guide the eye and does not represent model fit to data.

View larger version (20K): [in a new window]   FIGURE 5. HPLC radiochromatogram of [18F]FHBG and its metabolites in plasma taken 60 min after injection from cynomolgus monkey. For study shown, 86% of recovered activity was on [18F]FHBG as calculated by FHBG peak area ÷ total area under radiochromatogram.

View larger version (39K): [in a new window]   FIGURE 6. Distribution of 18F from [18F]FHBG in cynomolgus monkey. Images are coronal (left) and sagittal (right) 2-dimensional projections from multicouch-position scan obtained 104–140 min after intravenous injection of [18F]FHBG. Note that skeleton is not visualized, indicating that 18F uptake in bone and marrow was relatively low.

View larger version (43K): [in a new window]   FIGURE 7. Biodistribution of radiolabel from [18F]FHBG and [18F]FHPG in nude mice bearing transduced tumors. (A) Uptake at 2 h after injection. (B) Uptake at 5 h after injection. (C) Tumor-to-normal ratios at 2 h after injection. (D) Tumor-to-normal ratios at 5 h after injection. Data are mean ± SEM (n = 5). *P < 0.05 for difference between FHPG and FHBG.