Research ArticleBasic Science Investigations

Diabody Pretargeting with Click Chemistry In Vivo

Sander M.J. van Duijnhoven, Raffaella Rossin, Sandra M. van den Bosch, Michael P. Wheatcroft, Peter J. Hudson and Marc S. Robillard
Journal of Nuclear Medicine September 2015, 56 (9) 1422-1428; DOI: https://doi.org/10.2967/jnumed.115.159145

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Figures

  • FIGURE 1.
    FIGURE 1.

    (A) Schematic of diabody tumor pretargeting strategy based on inverse-electron-demand Diels–Alder reaction between TCO-tagged diabody and radiolabeled tetrazine. On tumor binding and blood clearance of diabody, administration of radiolabeled tetrazine targets radioactivity to prelocalized diabody in tumor. (B) Molecular structure of DOTA–tetrazine.

  • FIGURE 2.
    FIGURE 2.

    Blood clearance of 35 μg of 125I-AVP04-07, 125I-AVP04-07–TCO(1.8), and 125I-AVP04-07–TCO(4.7) in LS174T tumor–bearing mice. Data points represent mean ± SD %ID/g (n = 3). Half-lives were 1.92 h for 125I-AVP04-07, 3.30 h for 125I-AVP04-07–TCO(1.8), and 3.58 h for 125I-AVP04-07–TCO(4.7).

  • FIGURE 3.
    FIGURE 3.

    Dual-isotope biodistribution for pretargeting with 125I-AVP04-07, 125I-AVP04-07–TCO(1.8), or 125I-AVP04-07–TCO(4.7) and 177Lu-tetrazine in LS174T tumor–bearing mice. Mice were injected with one of the 125I-AVP04-07 diabodies, and 177Lu-tetrazine (10 Eq, with respect to diabody) was administered at 47 h after diabody injection. Mice were euthanized 3 h later. (A) Biodistribution of 125I-AVP04-07 diabodies. (B) Biodistribution of 177Lu-tetrazine. Bars represent mean ± SD %ID/g (n = 3). *P < 0.05. **P < 0.001.

  • FIGURE 4.
    FIGURE 4.

    177Lu-tetrazine biodistribution in LS174T tumor–bearing mice pretargeted with AVP04-07–TCO(4.7). Mice were injected with AVP04-07–TCO(4.7), and 177Lu-tetrazine (10 Eq [n = 3], 1.0 Eq, or 0.1 Eq [n = 4], with respect to diabody) was administered at 47 h after diabody injection. Mice were euthanized 3 h later. (A) Biodistribution of 177Lu-tetrazine. (B) Tumor-to-organ ratios for 177Lu-tetrazine. Bars represent mean ± SD. *P < 0.05. **P < 0.001.

  • FIGURE 5.
    FIGURE 5.

    SPECT/CT image (maximum-intensity projection) of 111In-tetrazine in LS174T tumor–bearing mouse pretargeted with AVP04-07–TCO(4.7). Image shows high radioactivity uptake in tumor (hind limb) and bladder (urine). Low retention of radioactivity was observed in kidneys, whereas all other organs and tissues showed negligible levels of radioactivity.

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