Abstract
The use of biologics in positron emission tomography (PET) imaging is an important area of radiopharmaceutical development and new automated methods are required to facilitate their production. We report an automated radiosynthesis method to produce a radiolabelled biologic via facile inverse electron demand Diels–Alder (IEDDA) “click” chemistry on a single GE FASTLab™ cassette. We exemplified the method by producing a fluorine-18 radiolabelled interleukin-2 (IL2) radioconjugate from a trans-cyclooctene (TCO) modified IL2 precursor. The radioconjugate was produced using a fully automated radiosynthesis on a single FASTLab™ cassette in a decay-corrected radiochemical yield (RCY, d.c.) of 19.8 ± 2.6% in 110 min (from start of synthesis); the molar activity was 132.3 ± 14.6 GBq μmol−1. The in vitro uptake of [18F]TTCO-IL2 correlated with the differential receptor expression (CD25, CD122, CD132) in PC3, NK-92 and activated human PBMCs. The automated method may be adapted for the radiosynthesis of any TCO-modified protein via IEDDA chemistry.
Highlights
The use and automation of 18F-prosthetic group (PG) strategies to radiolabel proteins is challenging for several reasons: 1. 18F-PG strategies can be challenging to synthesise
Cassette-based automated platforms have a limited capacity. These platforms are primarily designed for smallmolecule radiochemistry where SN2 18F-fluorination is followed by deprotection and a purification step; radiolabelling biomolecules through 18F-PG strategies is more complex in terms of i) number of synthetic steps, ii) types of purification strategy, iii) low reagent concentrations and iv) low volume reagent handling
Given the challenges faced in producing an efficient radiosynthesis of [18F]FB-IL2, and its clinical relevance, we developed an automated inverse electron demand Diels–Alder (IEDDA) “click” method to radiolabel a novel TCO-modified IL2 conjugate (TCO-PEG4-IL2) that we produced for this project
Summary
There is a precedent for PET and SPECT IL2 radioconjugates to been administered at
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