Theranostic radiolabeled anti-CD20 sdAb for targeted radionuclide therapy of non-hodgkin lymphoma

Abstract

Anti-CD20 radioimmunotherapy is an effective approach for bearing hCD20pos tumors. Radiolabeled with 68Ga, sdAb therapy of relapsed or refractory CD20pos lymphomas, but faces 9079 showed specific tumor uptake, with very low accumula-limitations due to poor tumor penetration and undesirable tion in nontarget organs, except kidneys. The tumor uptake pharmacokinetics of full antibodies. Camelid single-domain of 177Lu-DTPA-sdAb 9079 after 1.5 h was 3.4 1.3% ID/g, with Ab fragments (sdAb) might circumvent some of the limitations T/B and T/M ratios of 13.3 4.6 and 32.9 15.6. Peak tumor of radiolabeled full antibodies. In this study, a set of hCD20-accumulation of 177Lu-DTPA-rituximab was about 9 times targeting sdAbs was generated, and their capacity to bind higher, but concomitantly with high accumulation in nontarget hCD20 was evaluated in vitro and in vivo. A lead sdAb, sdAb organs and very low T/B and T/M ratios (0.8 0.1 and 7.1 9079, was selected on the basis of its specific tumor targeting 2.4). Treatment of mice with 177Lu-DTPA-sdAb 9079 signifi- and significant lower kidney accumulation compared with cantly prolonged median survival compared with control other sdAbs. SdAb 9079 was then radiolabeled with 68Ga and groups and was as effective as treatment with rituximab or its 177Lu for PET imaging and targeted therapy. The therapeutic 177Lu-labeled variant. Taken together, sdAb 9079 displays potential of 177Lu-DTPA-sdAb was compared with that promising features as a theranostic drug to treat CD20pos of 177Lu-DTPA-rituximab and unlabeled rituximab in mice lymphomas.