2014
DOI: 10.1021/mp500275a
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Trans-Cyclooctene Tag with Improved Properties for Tumor Pretargeting with the Diels–Alder Reaction

Abstract: Radioimmunotherapy (RIT) of solid tumors is hampered by low tumor-to-nontumor (T/NT) ratios of the radiolabeled monoclonal antibodies resulting in low tumor doses in patients. Pretargeting technologies can improve the effectiveness of RIT in cancer therapy by increasing this ratio. We showed that a pretargeting strategy employing in vivo chemistry in combination with clearing agents, proceeds efficiently in tumor-bearing mice resulting in high T/NT ratios. A dosimetry study indicated that the chemical pretarge… Show more

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Cited by 103 publications
(122 citation statements)
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“…5). This finding was expected because we and others previously demonstrated similar biodistributions of 177 Lu-and 111 In-labeled mAbs and low-molecular-weight agents when DOTA was used as a chelator (25,(27)(28)(29)(30).…”
Section: Optimization Of 177 Lu-tetrazine Dose To Improve Tumor Uptaksupporting
confidence: 70%
“…5). This finding was expected because we and others previously demonstrated similar biodistributions of 177 Lu-and 111 In-labeled mAbs and low-molecular-weight agents when DOTA was used as a chelator (25,(27)(28)(29)(30).…”
Section: Optimization Of 177 Lu-tetrazine Dose To Improve Tumor Uptaksupporting
confidence: 70%
“…Most literature examples of click-chemistry-based antibody pretargeting have involved non-internalizing targets, many of which were cell-surface glycans such as TAG-72 2932 and the transmembrane glycoprotein A33. 4,22 Use of a non-internalizing target is conceptually easier because it avoids the complication of receptor turnover, a process that could potentially deplete the available pool of antibody-TCO at the cell surface where click reaction is desirable.…”
Section: Discussionmentioning
confidence: 99%
“…This may be achieved through further studies with the use of FcRn mutations or clearing agents. 31,32 …”
Section: Discussionmentioning
confidence: 99%
“…6,7 Due to poor in vivo pharmacokinetics or other limitations of a traditional direct conjugate, pretargeting has been shown to improve imaging capabilities under different modalities in animal models. 8-16 Moreover, the small size of bioorthogonal reactants enable antibodies to act as scaffolds for the attachment of numerous nanomaterial probes to cells and microvesicles, leading to dramatic signal amplification for in vitro cultures and ex vivo human clinical specimens. 17-27 …”
Section: Introductionmentioning
confidence: 99%