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High-level production of alpha-particle-emitting (211)At and preparation of (211)At-labeled antibodies for clinical use.

Publication ,  Journal Article
Zalutsky, MR; Zhao, XG; Alston, KL; Bigner, D
Published in: J Nucl Med
October 2001

UNLABELLED: 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 alpha-particle emitter (211)At 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 (211)At and the radiosynthesis of clinically useful amounts of (211)At-labeled human/mouse chimeric 81C6 antibody. METHODS: (211)At was produced through the (209)Bi(alpha, 2n)(211)At reaction using an internal target system and purified by a dry distillation process. Antibody labeling was accomplished by first synthesizing N-succinimidyl 3-[(211)At]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 microA alpha-particles and irradiation times of 1.5-4.5 h, the mean (211)At production yield was 27.75 +/- 2.59 MBq/microA.h, and the maximum level of (211)At produced was 6.59 GBq after a 4-h irradiation at 55 microA. The decay-corrected distillation yield was 67% +/- 16%. The yield for the coupling of the (211)At-labeled active ester to the antibody was 76% +/- 8%. The fraction of (211)At 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 <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 (211)At-labeled antibodies and have permitted the initiation of a phase I trial of (211)At-labeled chimeric 81C6 administered directly into the tumor resection cavities of brain tumor patients.

Duke Scholars

Published In

J Nucl Med

ISSN

0161-5505

Publication Date

October 2001

Volume

42

Issue

10

Start / End Page

1508 / 1515

Location

United States

Related Subject Headings

  • Tenascin
  • Recombinant Fusion Proteins
  • Radioimmunotherapy
  • Nuclear Medicine & Medical Imaging
  • Isotope Labeling
  • Immunoconjugates
  • Astatine
  • Antibodies, Monoclonal
  • Alpha Particles
  • 3202 Clinical sciences
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Zalutsky, M. R., Zhao, X. G., Alston, K. L., & Bigner, D. (2001). High-level production of alpha-particle-emitting (211)At and preparation of (211)At-labeled antibodies for clinical use. J Nucl Med, 42(10), 1508–1515.
Zalutsky, M. R., X. G. Zhao, K. L. Alston, and D. Bigner. “High-level production of alpha-particle-emitting (211)At and preparation of (211)At-labeled antibodies for clinical use.J Nucl Med 42, no. 10 (October 2001): 1508–15.
Zalutsky MR, Zhao XG, Alston KL, Bigner D. High-level production of alpha-particle-emitting (211)At and preparation of (211)At-labeled antibodies for clinical use. J Nucl Med. 2001 Oct;42(10):1508–15.
Zalutsky, M. R., et al. “High-level production of alpha-particle-emitting (211)At and preparation of (211)At-labeled antibodies for clinical use.J Nucl Med, vol. 42, no. 10, Oct. 2001, pp. 1508–15.
Zalutsky MR, Zhao XG, Alston KL, Bigner D. High-level production of alpha-particle-emitting (211)At and preparation of (211)At-labeled antibodies for clinical use. J Nucl Med. 2001 Oct;42(10):1508–1515.

Published In

J Nucl Med

ISSN

0161-5505

Publication Date

October 2001

Volume

42

Issue

10

Start / End Page

1508 / 1515

Location

United States

Related Subject Headings

  • Tenascin
  • Recombinant Fusion Proteins
  • Radioimmunotherapy
  • Nuclear Medicine & Medical Imaging
  • Isotope Labeling
  • Immunoconjugates
  • Astatine
  • Antibodies, Monoclonal
  • Alpha Particles
  • 3202 Clinical sciences