Astatine-211 labeling of internalizing anti-EGFRvIII monoclonal antibody using N-succinimidyl 5-[At-211]astato-3-pyridinecarboxylate

Monoclonal antibodies (MAbs) such as the anti-epidermal growth factor varia nt III (EGFRvIII) MAb L8A4 are rapidly internalized, which can lead to rapi d loss of radioactivity from the tumor cell. The aim of this study was to e valuate the potential utility of N-succinimidyl 5-[At-211]astato-3-pyridine carboxylate ([At-211]SAPC) for labeling murine L8A4 with At-211. SAPC was s ynthesized by astatodestannylation of N-succinimidyl 5-tri-n-butylstannyl 3 -pyridinecarboxylate and then coupled to L8A4 in approximately 50% yield. T he affinity and immunoreactive fraction for At-211-labeled L8A4 were compar able to those obtained when the MAb was labeled with I-131 via N-succinimid yl 5-[I-131]iodo-3- pyridinecarboxylate (SIPC). Paired-label comparisons of the At-211- and I-131-labeled MAbs demonstrated similar internalization an d catabolism by EGFRvIII-positive cells in vitro, and with the exception of the stomach, similar tissue distribution in athymic mice with EGFRvIII-exp ressing U87 Delta EGFR xenografts. These results suggest that SAPC may be a useful reagent for Labeling L8A4, and possibly other internalizing protein s, with At-211. NUCL MED BIOL 26;4:405-411, 1999. (C) 1999 Elsevier Science Inc. All rights reserved.