OtherBASIC SCIENCE INVESTIGATIONS

Monodispersed DOTA-PEG–Conjugated Anti-TAG-72 Diabody Has Low Kidney Uptake and High Tumor-to-Blood Ratios Resulting in Improved 64Cu PET

Lin Li, Fabio Turatti, Desiree Crow, James R. Bading, Anne-Line Anderson, Erasmus Poku, Paul J. Yazaki, Lawrence E. Williams, Debra Tamvakis, Paul Sanders, David Leong, Andrew Raubitschek, Peter J. Hudson, David Colcher and John E. Shively
Journal of Nuclear Medicine July 2010, 51 (7) 1139-1146; DOI: https://doi.org/10.2967/jnumed.109.074153

Article Figures & Data

Figures

  • FIGURE 1. 
    FIGURE 1. 

    Biodistributions of unconjugated and DOTA-Cys-VS-PEG3400–conjugated AVP04-07 measured in athymic mice bearing LS-174T xenografts: 111In-labeled non-PEGylated diabody (A), 125I-labeled intact diabody (B), and 111In-labeled PEG3400 conjugated diabody (C).

  • FIGURE 2. 
    FIGURE 2. 

    Size-exclusion chromatography of radiolabeled non-PEGylated AVP04-07 diabody and its PEG conjugates. All samples were radiolabeled with 111In and run on Superdex 75 size-exclusion column (radioactivity in arbitrary units). Black = DOTA-non-PEGylated diabody conjugate; red = DOTA-Cys-VS-PEG3400 diabody conjugate; green = DOTA-PEG27-Cys-VS diabody conjugate; blue = DOTA-PEG12-Cys-VS diabody conjugate.

  • FIGURE 3. 
    FIGURE 3. 

    Biodistributions of DOTA-PEG27-Cys-VS-AVP04-07 and DOTA-PEG12-Cys-VS-AVP04-07 measured in athymic mice bearing LS-174T xenografts: 111In-labeled PEG27 conjugate (A), 125I-labeled PEG27 conjugate (B), 111In-labeled PEG12 conjugate (C), and 125I-labeled PEG12 conjugate (D).

  • FIGURE 4. 
    FIGURE 4. 

    High-resolution nanospray mass spectrometry analysis of PEG12 AVP04-07 conjugates: raw mass spectrum for non-PEGylated diabody (inset: deconvoluted spectrum) (A), deconvolved spectrum for PEG12 conjugate 20:1 (B), and deconvolved spectrum for PEG12 conjugate 50:1 (C).

  • FIGURE 5. 
    FIGURE 5. 

    Serial PET of 64Cu AVP04-07 and PEGylated AVP04-07 in athymic mice peripherally xenografted with TAG-72–expressing LS-174T colon tumors. Images are PET anterior-view maximum intensity projections normalized to reflect radiodecay-corrected relative image intensity per unit injected activity. Labels in red, green, yellow, and turquoise, respectively, show percentage injected dose (%ID)/g in blood (heart), liver, kidney, and tumor as measured by direct assay after final scan: 64Cu-AVP04-07 (A), 64Cu-PEG12 AVP04-07 (B), and 64Cu-PEG27 AVP04-07 (C).

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