Direct fluorine-18 labeling of heat-sensitive biomolecules for positron emission tomography imaging using the Al18F-RESCA method

  • Nat Protoc. 2018 Oct;13(10):2330-2347. doi: 10.1038/s41596-018-0040-7.
Frederik Cleeren  1 ,  Joan Lecina  1 ,  Jessica Bridoux  2 ,  Nick Devoogdt  2 ,  Térence Tshibangu  1 ,  Catarina Xavier  2 ,  Guy Bormans  3
Affiliations
  • 1. Radiopharmaceutical Research, Department of Pharmacy and Pharmacology, University of Leuven, Leuven, Belgium.
  • 2. In Vivo Cellular and Molecular Imaging Center, Vrije Universiteit Brussel, Brussels, Belgium.
  • 3. Radiopharmaceutical Research, Department of Pharmacy and Pharmacology, University of Leuven, Leuven, Belgium. [email protected].
PMID: 30250289 DOI: 10.1038/s41596-018-0040-7
Abstract

Positron emission tomography (PET) is a quickly expanding, non-invasive molecular imaging technology, and there is high demand for new specific imaging probes. Herein, we present a generic protocol for direct radiolabeling of heat-sensitive biomolecules with the positron-emitting radioisotope fluorine-18 (18F) using the aluminum fluoride restrained complexing agent (Al18F-RESCA) method. The Al18F-RESCA method combines the chemical advantages of a chelator-based radiolabeling method with the unique physical properties of the radionuclide of choice, fluorine-18. Proteins of interest can be conjugated to RESCA via amine coupling using (±)-H3RESCA-TFP, followed by purification using size-exclusion chromatography (SEC). Next, RESCA-derivatized biomolecules can be labeled in one step, at room temperature (~20 °C) in an aqueous medium with aluminum fluoride (Al18F). Al18F-labeled proteins can be obtained with moderate (12-17 GBq/µmol) to good (80-85 GBq/µmol) apparent molar activity, depending on the starting activity of 18F-. In addition, satisfactory radiochemical yields (35-55%, non-decay corrected) and high radiochemical purity (>98%, using gel filtration or solid-phase purification) are obtained. The mild radiolabeling procedure takes 0.5 h to complete and can be used for direct labeling of vector molecules such as peptides, protein scaffolds, and engineered antibody fragments.

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