RT Journal Article SR Electronic T1 Human Pharmacokinetic and Dosimetry Studies of [18F]FHBG: A Reporter Probe for Imaging Herpes Simplex Virus Type-1 Thymidine Kinase Reporter Gene Expression JF Journal of Nuclear Medicine JO J Nucl Med FD Society of Nuclear Medicine SP 1225 OP 1234 VO 42 IS 8 A1 Shahriar Yaghoubi A1 Jorge R. Barrio A1 Magnus Dahlbom A1 Meera Iyer A1 Mohammad Namavari A1 Nagichettiar Satyamurthy A1 Robin Goldman A1 Harvey R. Herschman A1 Michael E. Phelps A1 Sanjiv S. Gambhir YR 2001 UL http://jnm.snmjournals.org/content/42/8/1225.abstract AB 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 Warmed hand-vein blood was withdrawn at various times after injection for blood time–activity measurements.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.