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Synthesis and Biologic Study of IV-14, a New Ribonucleoside Radiotracer for Tumor Visualization

Boris D. Zlatopolskiy, Agnieszka Morgenroth, Falk H.-G. Kunkel, Elizaveta A. Urusova, Cornelia Dinger, Thomas Kull, Christian Lepping and Sven N. Reske
Journal of Nuclear Medicine November 2009, 50 (11) 1895-1903; DOI: https://doi.org/10.2967/jnumed.109.065623

Article Figures & Data

Figures

  • FIGURE 1. 
    FIGURE 1. 

    Structures of 3′-(ethynyl)uridine (EUrd) and 3′-(ethynyl)cytidine (ECyt) and metabolic activation of 3′-(ethynyl)uridine and 3′-(ethynyl)cytidine. UMP-CMP kinase = uridine monophosphate/cytidine monophosphate kinase; MP = monophosphate; DP = diphosphate; TP = triphosphate.

  • FIGURE 2. 
    FIGURE 2. 

    Synthesis of TBSVU, IV-14, and 123/131I-IV-14. EUrd = 3′-(ethynyl)uridine; RP = radiochemical purity; RCY = radiochemical yield.

  • FIGURE 3. 
    FIGURE 3. 

    Cellular uptake of 131I-IV-14 (100 kBq) in different tumor cell lines (A) and Western blot analysis of UCK1 and UCK2 expression in tumor cell lines studied (B). Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) expression is given as loading control.

  • FIGURE 4. 
    FIGURE 4. 

    (A) Dependence of cellular uptake of 131I-IV-14 in HL60 and Mia-PaCa-2 cells on pretreatment with 5-fluoro-2′-deoxyuridine (FdUrd), 5-fluorouridine (FUrd), and p-nitrobenzylmercaptopurine (NBMPR). (B) Cellular distribution of 131I-IV-14 in HL60 cells. (C) Metabolism of 131I-IV-14 by Mia-PaCa-2 cells (M-1 = metabolite 1; M-2 = metabolite 2; M-3 = metabolite 3). (D) Hydrolysis of M-1–M-3 by calf intestinal alkaline phosphatase (CIAP).

  • FIGURE 5. 
    FIGURE 5. 

    Biodistribution of 131I-IV-14 (10 MBq) in HL60-xenografted SCID mice 30 and 60 min after injection (A) and 4 and 24 h after injection (B). Relative account of radioactivity/g in tissue divided by that in tumor (tissue-to-tumor ratio) 30 min after injection: tumor, 1.0 ± 0.15; kidneys, 2.69 ± 1.30; liver, 1.47 ± 0.81; small intestine, 1.48 ± 0.66; spleen, 1.38 ± 0.44. Tissue-to-tumor ratio 4 h after injection: tumor, 1 ± 0.24; spleen, 0.40 ± 0.18; colon, 0.25 ± 0.12; bones, 0.18 ± 0.18; small intestine, 0.14 ± 0.07; others, <0.1. Five animals were used at each time point.

  • FIGURE 6. 
    FIGURE 6. 

    At top left is scintigraph obtained with 123I-IV-14 (20 MBq; 4 h) in 3 HL60-xenografted SCID mice. At bottom left is Western blot analysis of UCK1 and UCK2 expression in HL60 xenograft, spleen, small intestine, and liver tissues. Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) was used as loading control. At right is analysis of metabolites of 131I-IV-14 (4 h after injection) in HL60-xenografted SCID mice. M-1 = metabolite 1; M-2 = metabolite 2.

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