About the Cover
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ABOUT THE COVER
By decoupling the targeting vector from the radioactivity at the time of injection, pretargeting strategies offer an enticing way to combine the exquisite selectivity and affinity of mAbs with the favorable pharmacokinetics of small molecules. In this issue, Houghton and colleagues report the development of a strategy for pretargeted radioimmunotherapy (PRIT) based on the extraordinarily rapid and bioorthogonal inverse electron demand Diels-Alder reaction between tetrazine (Tz) and trans-cyclooctene (TCO). The authors report that PRIT using a 177Lu-labeled Tz radioligand (177Lu-DOTA-PEG7-Tz) and a TCO-bearing immunoconjugate of the CA19.9-targeting antibody 5B1 (5B1-TCO) resulted in a dose-dependent reduction in tumor volume in a murine model of pancreatic ductal adenocarcinoma. See article (beginning on p. 124) for more information.