Enzymatic fluorination of biotin and tetrazine conjugates for pretargeting approaches to PET imaging

Phillip T. Lowe, Sergio Dall'angelo, Andrew Devine, Matteo Zanda, David O'Hagan

Research output: Contribution to journalArticlepeer-review

8 Citations (Scopus)
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Abstract

The use of radiolabelled antibodies and antibody‐derived recombinant constructs has shown promise for both imaging and therapeutic use. In this context, the biotin–avidin/streptavidin pairing, along with the inverse‐electron‐demand Diels–Alder (iEDDA) reaction, have found application in pretargeting approaches for positron emission tomography (PET). This study reports the fluorinase‐mediated transhalogenation [5′‐chloro‐5′‐deoxyadenosine (ClDA) substrates to 5′‐fluoro‐5′‐deoxyadenosine (FDA) products] of two antibody pretargeting tools, a FDA‐PEG‐tetrazine and a [18F]FDA‐PEG‐biotin, and each is assessed either for its compatibility towards iEDDA ligation to trans‐cyclooctene or for its affinity to avidin. A protocol to avoid radiolytically promoted oxidation of biotin during the synthesis of [18F]FDA‐PEG‐biotin was developed. The study adds to the repertoire of conjugates for use in fluorinase‐catalysed radiosynthesis for PET and shows that the fluorinase will accept a wide range of ClDA substrates tethered at C‐2 of the adenine ring with a PEGylated cargo. The method is exceptional because the nucleophilic reaction with [18F]fluoride takes place in water at neutral pH and at ambient temperature.
Original languageEnglish
JournalChemBioChem
VolumeIn press
Early online date8 Aug 2018
DOIs
Publication statusE-pub ahead of print - 8 Aug 2018

Keywords

  • Fluorinase
  • Amide bioconjugation
  • Tetrazine
  • Biotin
  • 18F labelling

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