RT Journal Article SR Electronic T1 Comparison of Radiolabeled Nucleoside Probes (FIAU, FHBG, and FHPG) for PET Imaging of HSV1-tk Gene Expression JF Journal of Nuclear Medicine JO J Nucl Med FD Society of Nuclear Medicine SP 1072 OP 1083 VO 43 IS 8 A1 Juri Gelovani Tjuvajev A1 Mikhail Doubrovin A1 Timothy Akhurst A1 Shangde Cai A1 Julius Balatoni A1 Mian M. Alauddin A1 Ronald Finn A1 William Bornmann A1 Howard Thaler A1 Peter S. Conti A1 Ronald G. Blasberg YR 2002 UL http://jnm.snmjournals.org/content/43/8/1072.abstract AB The efficacy of 3 radiolabeled probes of current interest for imaging herpes simplex virus type 1 thymidine kinase (HSV1-tk) expression in vivo with PET, including 124I- or 131I-labeled 2′-fluoro-2′-deoxy-1-β-d-arabinofuranosyl-5-iodouracil (FIAU), 18F-labeled 9-[4-fluoro-3-(hydroxymethyl)butyl]guanine (FHBG), and 18F-labeled 9-[3-fluoro-1-hydroxy-2-propoxymethyl]guanine (FHPG), was compared. Methods: Two established rat glioma cell lines, stably transduced RG2TK+ and wild-type RG2, were used for paired comparisons of probe accumulation in vitro and for paired comparisons of subcutaneous xenografts produced from these cell lines in athymic rnu/rnu rats. Results: The in vitro paired probe uptake (0–3 h) comparisons in RG2TK+ cells showed that FIAU accumulation was 15-fold greater than that of FHBG and 41-fold greater than that of FHPG. The net accumulation rate values (±SD) calculated for RG2TK+ cells were 0.317 ± 0.066, 0.022 ± 0.001, and 0.0077 ± 0.0003 mL/min/g cells for FIAU, FHBG, and FHPG, respectively. These results and similar uptake studies in RG2 wild-type cells suggest a possible cell membrane transport limitation for FHBG and FHPG. The paired 2-h in vivo uptake studies produced similar differences in RG2TK+ xenografts for FIAU and FHBG (1.22 ± 0.21 vs. 0.074 ± 0.49 %dose/g) and for FIAU and FHPG (1.27 ± 0.14 vs. 0.023 ± 0.008 %dose/g). These differences were clearly visible on the images. FIAU accumulation at 24 h was 1.53 ± 0.40 %dose/g. Plasma clearance was FHBG > FHPG ≫ FIAU. The FIAU images showed significant stomach and some intestinal background radioactivities, whereas hepatobiliary and intestinal background activities were very high for the guanosine analogs (FHBG > FHPG). Dynamic imaging showed early (∼10 min) selective localization of FIAU in RG2TK+ xenografts, whereas FHBG and FHPG are being cleared from the HSV1-tk transduced and wild-type xenografts over the initial 2-h imaging period. Conclusion: The in vitro and in vivo results (including the PET images) show that FIAU is a substantially more efficient probe than FHBG or FHPG for imaging HSV1-tk expression, with greater sensitivity and contrast as well as lower levels of abdominal background radioactivity at 2 and 24 h.