A biorthogonal chemistry approach for high-contrast antibody imaging of lymphoma at early time points
Sarkar S, Pham JM, Edwards KJ, Sharma N, Xu K, King AP, Del Castillo AF, Farwell MD, Pryma DA, Schuster SJ, Sellmyer MA. A biorthogonal chemistry approach for high-contrast antibody imaging of lymphoma at early time points. EJNMMI Res. 2025 Mar 24;15(1):26. doi: 10.1186/s13550-025-01213-x. PMID: 40122966; PMCID: PMC11930911.
Abstract
Background: Monoclonal 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.