18F-Based Pretargeted PET Imaging Based on Bioorthogonal Diels–Alder Click Chemistry

作者：Jan‐Philip Meyer, Jacob L. Houghton, Paul M. Kozlowski, Dalya Abdel-Atti, Thomas Reiner, Nagavarakishore Pillarsetty, Wolfgang W. Scholz, Brian M. Zeglis, Jason Stuart Lewis · 发表于：Bioconjugate Chemistry · 年份：2015 · DOI：10.1021/acs.bioconjchem.5b00504 · 被引用次数：168 · 研究领域：Click Chemistry and Applications、Monoclonal and Polyclonal Antibodies Research、Radiopharmaceutical Chemistry and Applications

A first-of-its-kind (18)F pretargeted PET imaging approach based on the bioorthogonal inverse electron demand Diels-Alder (IEDDA) reaction between tetrazine (Tz) and trans-cyclooctene (TCO) is presented. As proof-of-principle, a TCO-bearing immunoconjugate of the anti-CA19.9 antibody 5B1 and an Al[(18)F]NOTA-labeled tetrazine radioligand were harnessed for the visualization of CA19.9-expressing BxPC3 pancreatic cancer xenografts. Biodistribution and (18)F-PET imaging data clearly demonstrate that this methodology effectively delineates tumor mass with activity concentrations up to 6.4 %ID/g at 4 h after injection of the radioligand.