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BASIC SCIENCE INVESTIGATIONS |
Crump Institute for Molecular Imaging, UCLA–DOE Laboratory of Structural Biology and Molecular Medicine; Department of Molecular and Medical Pharmacology, Division of Nuclear Medicine; Molecular Biology Institute; Department of Biomathematics; and Jonsson Comprehensive Cancer Center, UCLA School of Medicine, University of California, Los Angeles, California
9-[4-[18F]fluoro-3-(hydroxymethyl)butyl]guanine ([18F]FHBG) has been used as a reporter probe to image expression of herpes simplex virus type-1 thymidine kinase (HSV1-tk) reporter gene in living animals. Our aim was to study the kinetics, biodistribution, stability, dosimetry, and safety of [18F]FHBG in healthy human volunteers, preparatory to imaging patients undergoing HSV1-tk gene therapy. Methods: [18F]FHBG was synthesized with a specific activity of 37,000–444,000 GBq/mmol and a radiochemical purity > 99%. Ten healthy volunteers consented to participate in the study. A transmission scan was obtained before bolus injection of 70.3–229.4 MBq [18F]FHBG into a hand vein, followed by dynamic PET imaging with 4 consecutive emission scans. Warmed hand-vein blood was withdrawn at various times after injection for blood time–activity measurements. Electrocardiography, blood pressure, and blood and urine pharmacologic parameters were measured before and after injection of the [18F]FHBG tracer (n = 5). The stability of [18F]FHBG in the urine was analyzed. Attenuation-corrected images were reconstructed using the ordered-subsets expectation maximization algorithm. Image region-of-interest time–activity data were used with the MIRD program to estimate absorbed radiation dosages. Results: [18F]FHBG had rapid blood clearance; only 8.42% ± 4.76% (mean ± SD) of the peak blood activity remained at approximately 30 min. The average ratio of plasma activity to whole-blood activity during the study was 0.91 ± 0.04. Penetration of [18F]FHBG across the blood–brain barrier was not observed. The primary routes of clearance were renal and hepatobiliary. High activities were observed in the bladder, gut, liver, and kidneys, but <0.0002% of the injected dose per gram was observed in other tissues. In the urine, 83% of activity 180 min after injection was stable [18F]FHBG. Blood and urine pharmacologic parameters did not change significantly after injection of the [18F]FHBG tracer. The bladder absorbed the highest radiation dose. Conclusion: [18F]FHBG has the desirable in vivo characteristics of stability, rapid blood clearance, low background signal, biosafety, and acceptable radiation dosimetry in humans. This study forms the foundation for using [18F]FHBG in applications to monitor HSV1-tk reporter gene expression.
Key Words: 9-[4-[18F]fluoro-3-(hydroxymethyl)butyl]guanine • dosimetry • PET • herpes simplex virus type-1 thymidine kinase
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