Journal of Nuclear Medicine | |
Human Pharmacokinetic and Dosimetry Studies of [18F]FHBG: A Reporter Probe for Imaging Herpes Simplex Virus Type-1 Thymidine Kinase Reporter Gene Expression | |
Michael E. Phelps1  Jorge R. Barrio1  Shahriar Yaghoubi1  Harvey R. Herschman1  Mohammad Namavari1  Nagichettiar Satyamurthy1  Robin Goldman1  Sanjiv S. Gambhir1  Meera Iyer1  Magnus Dahlbom1  | |
[1] 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 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 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 | |
关键词: 9-[4-[18F]fluoro-3-(hydroxymethyl)butyl]guanine; dosimetry; PET; herpes simplex virus type-1 thymidine kinase; | |
DOI : | |
学科分类:医学(综合) | |
来源: Society of Nuclear Medicine | |
【 摘 要 】
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 Warmed hand-vein blood was withdrawn at various times after injection for blood time–activity measurements.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.
【 授权许可】
Unknown
【 预 览 】
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RO201912010195084ZK.pdf | 820KB | download |