Astatine-211 conjugated to an anti-CD20 monoclonal antibody eradicates disseminated B-cell lymphoma in a mouse model

Abstract

α-Emitting radionuclides deposit a large amount of energywithin a fewcell diameters andmay be particularly effective for radioimmunotherapy targeting minimal residual disease (MRD). To evaluate this hypothesis, 211At-labeled 1F5monoclonal antibody (mAb) (anti-CD20)was studied in both bulky lymphoma tumor xenograft and MRD animal models. Superior treatment responses to 211At-labeled 1F5 mAb were evident in the MRD setting. Lymphoma xenograft tumor-bearing animals treatedwith doses of up to 48 μCi of211At-labeled anti-CD20mAb ([211At]1F5-B10) experiencedmodest responses(0%curesbut two- tothreefoldprolongationof survival compared with negative controls). In contrast, 70% of animals in the MRD lymphoma model demonstrated complete eradication of disease when treated with 211At-B10-1F5 at a radiation dose that was less than one-third (15 μCi) of the highest dose given to xenograft animals. Tumor progression among untreated control animals in both models was uniformly lethal. After 130 days, no significant renal or hepatic toxicity was observed in the cured animals receiving 15 μCi of [211At]1F5-B10. These findings suggest that a-emitters are highly efficacious in MRD settings, where isolated cells and small tumor clusters prevail.