ArticleEJNMMI research2025
A biorthogonal chemistry approach for high-contrast antibody imaging of lymphoma at early time points.
Article in EJNMMI research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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Who cites it
2 citing papers in PubMed.
- Dual-modal tumor-selective benzofuran tracer integrating real-time imaging and anticancer effects.Acta pharmaceutica Sinica. B · 2026Article
- Linker Chemistry in Radiopharmaceutical Design.Bioconjugate chemistry · 2026Review
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Authors and funding
11 authors.
Funding
Abstract
backgroundMonoclonal antibodies are highly specific for their targets making them effective for cancer therapy. However, their large molecular weight causes slow blood clearance, often requiring weeks to be removed from circulation. This limitation affects companion nuclear imaging and antibody-based diagnostics, necessitating delayed imaging. We report the expansion of a methodology improving positron emission tomography (PET) contrast of the lymphoma biomarker CD20 at early time points after radiolabeled antibody administration. Intact radioimmunoconjugates are allowed to stay in circulation long enough to accumulate in tumors, and then, using a chemical trigger, we induced rapid clearance of the radioactivity from non-target tissues by cleaving the linker between the antibody and the radioactivity. For brevity, we refer to the this as the Tetrazine KnockOut (TKO) method which uses the transcyclooctene-tetrazine (TCO-Tz) reaction, wherein an antibody is conjugated with linker containing TCO and a radioisotope.
resultsWe optimized the TCO linker with several different radioisotopes and evaluated the ability of tetrazines to knockout radioactivity from circulating antibodies. We explored several cell types and antibodies with varying internalization rates, to characterize the parameters of TKO and tested [
conclusionThe TKO approach potentiates early imaging of rituximab radioimmunoconjugates and has translational potential for lymphoma imaging.
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