RT Journal Article
SR Electronic
T1 High-Level Production of α-Particle–Emitting <sup>211</sup>At and Preparation of <sup>211</sup>At-Labeled Antibodies for Clinical Use
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 1508
OP 1515
VO 42
IS 10
A1 Michael R. Zalutsky
A1 Xiao-Guang Zhao
A1 Kevin L. Alston
A1 Darell Bigner
YR 2001
UL http://jnm.snmjournals.org/content/42/10/1508.abstract
AB In vitro and in vivo studies in human glioma models suggest that the antitenascin monoclonal antibody 81C6 labeled with the 7.2-h–half-life α-particle emitter 211At might be a valuable endoradiotherapeutic agent for the treatment of brain tumors. The purpose of this study was to develop methods for the production of high levels of 211At and the radiosynthesis of clinically useful amounts of 211At-labeled human/mouse chimeric 81C6 antibody. Methods: 211At was produced through the 209Bi(α, 2n)211At reaction using an internal target system and purified by a dry distillation process. Antibody labeling was accomplished by first synthesizing N-succinimidyl 3-[211At]astatobenzoate from the corresponding tri-n-butyl tin precursor and reacting it with the antibody in pH 8.5 borate buffer. Quality control procedures consisted of methanol precipitation, size-exclusion high-performance liquid chromatography (HPLC), and pyrogen and sterility assays, as well as determination of the immunoreactive fraction by a rapid procedure using a recombinant tenascin fragment coupled to magnetic beads. Results: A total of 16 antibody labeling runs were performed. Using beam currents of 50–60 μA α-particles and irradiation times of 1.5–4.5 h, the mean 211At production yield was 27.75 ± 2.59 MBq/μA.h, and the maximum level of 211At produced was 6.59 GBq after a 4-h irradiation at 55 μA. The decay-corrected distillation yield was 67% ± 16%. The yield for the coupling of the 211At-labeled active ester to the antibody was 76% ± 8%. The fraction of 211At activity that eluted with a retention time corresponding to intact IgG on HPLC was 96.0% ± 2.5%. All preparations had a pyrogen level of &lt;0.125 EU/mL and were determined to be sterile. The mean immunoreactive fraction for these 16 preparations was 83.3% ± 5.3%. Radiolysis did not interfere with labeling chemistry or the quality of the labeled antibody product. Conclusion: These results show that it is feasible to produce clinically relevant activities of 211At-labeled antibodies and have permitted the initiation of a phase I trial of 211At-labeled chimeric 81C6 administered directly into the tumor resection cavities of brain tumor patients.