Comparison of Radiolabeled Nucleoside Probes (FIAU, FHBG, and FHPG) for PET Imaging of HSV1-tk Gene Expression
Juri Gelovani Tjuvajev, MD, PhD1,2,
Mikhail Doubrovin, MD, PhD1,
Timothy Akhurst, MD2,3,
Shangde Cai, PhD4,
Julius Balatoni, PhD1,
Mian M. Alauddin, PhD5,
Ronald Finn, PhD2,4,
William Bornmann, PhD6,
Howard Thaler, PhD7,
Peter S. Conti, MD5 and
Ronald G. Blasberg, MD1,2
1 Department of Neurology, Memorial Sloan-Kettering Cancer Center, New York, New York
2 Department of Radiology, Memorial Sloan-Kettering Cancer Center, New York, New York
3 Nuclear Medicine Service, Memorial Sloan-Kettering Cancer Center, New York, New York
4 Radiochemistry/Cyclotron Core Facility, Memorial Sloan-Kettering Cancer Center, New York, New York
5 Department of Radiology, PET Imaging Science Center, University of Southern California, Los Angeles, California
6 Preparative Core Resource Facility, Memorial Sloan-Kettering Cancer Center, New York, New York
7 Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, New York
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FIGURE 2. Paired PET imaging studies comparing 124I-FIAU and 18F-FHBG or 18F-FHPG were performed. Coronal (A) and axial (B) PET images are shown for 3 different rats. Each animal had 2 imaging studies within 24 h, and comparable image pairs are shown in each quadrant of A and B. Location of RG2TK+ xenograft is indicated by arrow. Linear scaling of image intensity was performed to achieve similar background intensity on all images; background radioactivity in thorax was 0.013 and 0.027 %dose/g for animal 1, 0.024 and 0.18 %dose/g for animal 2, and 0.23 and 0.24 %dose/g for animal 3 (FHBG or FHPG and FIAU, respectively). No radioactivity above background is visualized in control RG2 xenograft. Several tissues had substantially higher values than indicated on intensity scale. For example, FIAU levels in RG2TK+ xenografts in animals 1–3 were 0.55, 1.7, and 1.2 %dose/g, respectively. Also note high values of radioactivity in stomach (6.0 %dose/g) and bladder (3.9 %dose/g) in 2-h study (animal 2). FHBG levels in abdominal viscera (2.8–3.2 %dose/g) and bladder (11 and 80 %dose/g) were also substantial at 2 h (animals 1 and 2); similar values were measured for FHPG in abdomen (3.4 %dose/g) and bladder (63 %dose/g) of animal 3. Note that FIAU bladder radioactivity had essentially cleared by 24 h (animals 1 and 3).
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FIGURE 3. Comparison of 10-min imaging frames of FIAU accumulation. Ten-minute coronal image frames through RG2TK+ and RG2 xenografts are shown at various times after intravenous injection of 124I-FIAU. Image intensity scale is same for all frames.
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FIGURE 4. Radioactivity-time profiles in RG2TK+ and RG2 xenografts after intravenous injection of 124I-FIAU, 18F-FHBG, and 18F-FHPG. Values (%dose/mL) are the mean ± SD (n = 6) of maximum pixel value measured in each xenograft. FHBG and FIAU data were obtained from same set of animals imaged on consecutive days.
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FIGURE 5. Chemical structures of pyrimidine (A) and acycloguanosine (B) nucleoside probes. IUdR = 2'-deoxy-5-iodo-1-ß-D-ribofuranosyl-uracil; BrUdR = 2'-deoxy-5-bromo-1-ß-D-ribofuranosyl-uracil.
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Copyright © 2002 by the Society of Nuclear Medicine.
) and 18F-FHPG-14C-FIAU (
) accumulation data (mL medium/g cells) are shown. (B) 18F-FHBG-14C-FIAU and 18F-FHPG-14C-FIAU comparisons with 3H-TdR are shown: 14C-FIAU (•), 18F-FHBG (
). Each point represents paired comparison of uptake results obtained from single triple-label experiment; experimental times varied between 10 and 180 min.