ImmunoPET imaging of B-cell lymphoma using 124I-anti-CD20 scFv dimers (diabodies)

Abstract

Edited by Paul CarterRapid clearing engineered antibody fragments for immunoPET promise high sensitivity at early time points. Here, tumor targeting of anti-CD20 diabodies (scFv dimers) for detection of low-grade B-cell lymphomas were evaluated. In addition, the effect of linker length on oligomerization of the diabody was investigated. Four rituximab scFv variants in the V L -V H orientation with different linker lengths between the V domains (scFv-1, scFv-3, scFv-5, scFv-8), plus the scFv-5 with a C-terminal cysteine (Cys-Db) for site-specific modification were generated. The scFv-8 and Cys-Db were radioiodinated with 124 I for PET imaging, and biodistribution of 131 I-Cys-Db was carried out at 2, 4 10 and 20 h. The five anti-CD20 scFv variants were expressed as fully functional dimers. Shortening the linker to three or one residue did not produce higher order of multimers. Both 124 I-labeled scFv-8 and Cys-Db exhibited similar tumor targeting at 8 h post injection, with significantly higher uptakes than in control tumors (P < 0.05). At 20 h, less than 1% ID/g of 131 I-labeled Cys-Db was present in tumors and tissues. Specific tumor targeting and high contrast images were achieved with the anti-CD20 diabodies. These agents extend the repertoire of reagents that can potentially be used to improve detection of low-grade lymphomas.

Radretumab Radioimmunotherapy in Patients with Brain Metastasis: A 124I-L19SIP Dosimetric PET Study

“…2 and 4; Table 1). Our results are consistent with those published by Wu and colleagues, who showed the advantages of using antibodies in mini-antibody format (functionally equivalent to SIP) and 124 I as a PET radionuclide (44,45).…”

A Novel Engineered Anti-CD20 Tracer Enables Early Time PET Imaging in a Humanized Transgenic Mouse Model of B-cell Non-Hodgkins Lymphoma

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Engineered antibody fragments for immuno-PET imaging of endogenous CD8 + T cells in vivo

“…Unlike the work presented here, the radiolabeled rituximab is still biologically active and not ideal for imaging studies. Engineering rituximab to other antibody formats could decrease the Fc-dependent biological activity of the imaging radiopharmaceutical (22,23). In the context of tumor targeting, this antigen sink has been overcome by blocking endogenous target with cold antibody either during (bolus injection) or before (predosing/blocking injection) administration of the radiotracer.…”