Manipulating the in vivo behaviour of68ga with tris(Hydroxypyridinone) chelators: Pretargeting and blood clearance

Cinzia Imberti*, Pierre Adumeau, Julia E. Blower, Fahad Al Salemee, Julia Baguña Torres, Jason S. Lewis, Brian M. Zeglis, Samantha Y.A. Terry, Philip J. Blower

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

9 Citations (Scopus)


Pretargeting is widely explored in immunoPET as a strategy to reduce radiation exposure of non-target organs and allow the use of short-lived radionuclides that would not otherwise be compatible with the slow pharmacokinetic profiles of antibodies. Here we investigate a pretargeting strategy based on gallium-68 and the chelator THPMe as a high-affinity pair capable of combining in vivo. After confirming the ability of THPMe to bind68Ga in vivo at low concentrations, the bifunctional THPMe-NCS was conjugated to a humanised huA33 antibody targeting the A33 glycoprotein. Imaging experiments performed in nude mice bearing A33-positive SW1222 colorectal cancer xenografts compared pretargeting (100 µg of THPMe-NCS-huA33, followed after 24 h by 8–10 MBq of68Ga3+) with both a directly labelled radioimmunoconjugate (89Zr-DFO-NCS-huA33, 88 µg, 7 MBq) and a68Ga-only negative control (8–10 MBq of68Ga3+). Imaging was performed 25 h after antibody administration (1 h after68Ga3+ administration for negative control). No difference between pretargeting and the negative control was observed, suggesting that pretargeting via metal chelation is not feasible using this model. However, significant accumulation of “unchelated”68Ga3+ in the tumour was found (12.9 %ID/g) even without prior administration of THPMe-NCS-huA33, though tumour-to-background contrast was impaired by residual activity in the blood. Therefore, the68Ga-only experiment was repeated using THPMe (20 µg, 1 h after68Ga3+ administration) to clear circulating68Ga3+, producing a three-fold improvement of the tumour-to-blood activity concentration ratio. Although preliminary, these results highlight the potential of THPMe as a68Ga clearing agent in imaging applications with gallium citrate.

Original languageEnglish
Article number1496
JournalInternational Journal of Molecular Sciences
Issue number4
Publication statusPublished - 2 Feb 2020


  • Bifunctional chelators
  • Gallium-68
  • Hydroxypyridinones
  • Metal chelation
  • Monoclonal antibodies
  • Pretargeting
  • Radionuclide imaging


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