journal contribution
posted on 2023-04-03, 16:00 authored by Ahmet Krasniqi, Matthias D'Huyvetter, Catarina Xavier, Kevin Van der Jeught, Serge Muyldermans, José Van Der Heyden, Tony Lahoutte, Jan Tavernier, Nick Devoogdt Ex vivo biodistribution of 177Lu-DTPA-sdAb 9077, 9079 and non-target control sdAb (177Lu-DTPA-ctrl sdAb) at 1.5 h p.i., co-infused with 150 mg/kg Gelofusin, in hCD20 B16 tumor mouse model. Results are presented as mean % IA/g {plus minus} SD (n = 3 per sdAb). T/M: Tumor-to-Muscle ratio; T/B: Tumor- to-Blood ratio.
Funding
Agentschap voor Innovatie door Wetenschap en Technologie
Wetenschappelijk Fonds Willy Gepts, Belgium
Damon Runyon Clinical Investigator Award
ERC Advanced Grant
History
ARTICLE ABSTRACT
Anti-CD20 radioimmunotherapy is an effective approach for therapy of relapsed or refractory CD20pos lymphomas, but faces limitations due to poor tumor penetration and undesirable pharmacokinetics of full antibodies. Camelid single-domain Ab fragments (sdAb) might circumvent some of the limitations of radiolabeled full antibodies. In this study, a set of hCD20-targeting sdAbs was generated, and their capacity to bind hCD20 was evaluated in vitro and in vivo. A lead sdAb, sdAb 9079, was selected on the basis of its specific tumor targeting and significant lower kidney accumulation compared with other sdAbs. SdAb 9079 was then radiolabeled with 68Ga and 177Lu for PET imaging and targeted therapy. The therapeutic potential of 177Lu-DTPA-sdAb was compared with that of 177Lu-DTPA-rituximab and unlabeled rituximab in mice bearing hCD20pos tumors. Radiolabeled with 68Ga, sdAb 9079 showed specific tumor uptake, with very low accumulation in nontarget organs, except kidneys. The tumor uptake of 177Lu-DTPA-sdAb 9079 after 1.5 h was 3.4 ± 1.3% ID/g, with T/B and T/M ratios of 13.3 ± 4.6 and 32.9 ± 15.6. Peak tumor accumulation of 177Lu-DTPA-rituximab was about 9 times higher, but concomitantly with high accumulation in nontarget organs and very low T/B and T/M ratios (0.8 ± 0.1 and 7.1 ± 2.4). Treatment of mice with 177Lu-DTPA-sdAb 9079 significantly prolonged median survival compared with control groups and was as effective as treatment with rituximab or its 177Lu-labeled variant. Taken together, sdAb 9079 displays promising features as a theranostic drug to treat CD20pos lymphomas. Mol Cancer Ther; 16(12); 2828–39. ©2017 AACR.
