Molecular imaging of tumors with nanobodies and antibodies: Timing and dosage are crucial factors for improved in vivo detection. (27th April 2015)

• Record Type: Journal Article
• Authors: Bannas, Peter; Lenz, Alexander; Kunick, Valentin; Well, Lennart; Fumey, William; Rissiek, Björn; Haag, Friedrich; Schmid, Joanna; Schütze, Kerstin; Eichhoff, Anna; Trepel, Martin; Adam, Gerhard; Ittrich, Harald; Koch‐Nolte, Friedrich
• Is Part Of: Contrast media & molecular imaging. Volume 10:Number 5(2015:Sep./Oct.)
• Page Start: 367
• Page End: 378
• Publication Date: 2015-04-27
• Subjects: Diagnostic imaging -- Periodicals; Magnetic resonance imaging -- Periodicals; Contrast media (Diagnostic imaging) -- Periodicals; Contrast Media -- Periodicals; Diagnostic Imaging -- Periodicals; Substances de contraste -- Périodiques; Diagnostics moléculaires -- Périodiques; Imagerie médicale; Substance de contraste; Périodique électronique (Descripteur de forme); Ressource Internet (Descripteur de forme); 616.0754
• DOI: 10.1002/cmmi.1637
• Languages: English
• ISSNs: 1555-4309

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p>The utility of nanobodies and conventional antibodies for <italic>in vivo</italic> imaging is well known, but optimum dosing and timing schedules for one versus the other have not been established. We aimed to improve specific tumor imaging <italic>in vivo</italic> with nanobodies and conventional antibodies using near‐infrared fluorescence (NIRF) imaging. We used ARTC2 expressed on lymphoma cells as a model target antigen. ARTC2‐specific nanobody s+16a and conventional antibody Nika102 were labeled with NIRF‐dye AF680. <italic>In vivo</italic> NIRF‐imaging of ARTC2‐positive and ARTC2‐negative xenografts was performed over 24 h post‐injection of 5, 10, 25, or 50 µg of each conjugate. Specific target‐binding and tissue‐penetration were verified by NIRF imaging <italic>ex vivo</italic>, flow cytometry and fluorescence microscopy. NIRF‐imaging of s+16a<sup>680</sup><italic>in vivo</italic> revealed a six times faster tumor accumulation than of Nika102<sup>680</sup>. Using 50 µg of s+16a<sup>680</sup> increased the specific signals of ARTC2‐positive tumors without increasing background signals, allowing a tumor‐to‐background (T/B) ratio of 12.4 ± 4.2 within 6 h post‐injection. Fifty micrograms of Nika102<sup>680</sup> increased specific signals of ARTC2‐positive tumors but also of ARTC2‐negative tumors and background, thereby limiting the T/B ratio to 6.1 ± 2.0. Ten micrograms of Nika102<sup>680</sup> only slightly reduced specific tumor signals but dramatically reduced background signals. <italic>Ex vivo</italic> analyses confirmed a faster and deeper tumor penetration with s+16a<sup>680</sup>. Using nanobody s+16a allowed same‐day imaging with a high T/B ratio, whereas antibody Nika102 gave optimal imaging results only 24 h post injection. Nanobody s+16a required a high dose, whereas antibody Nika102 had the best T/B‐ratio at a low dose. Therefore, timing and dosage should be addressed when comparing nanobodies and conventional antibodies for molecular imaging purposes. Copyright © 2015 John Wiley & Sons, Ltd.</p> </abstract>