RT Journal Article
SR Electronic
T1 Direct Procedure for the Production of <sup>211</sup>At-Labeled Antibodies with an ε-Lysyl-3-(Trimethylstannyl)Benzamide Immunoconjugate
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 1537
OP 1545
DO 10.2967/jnumed.107.049833
VO 49
IS 9
A1 Lindegren, Sture
A1 Frost, Sofia
A1 Bäck, Tom
A1 Haglund, Elin
A1 Elgqvist, Jörgen
A1 Jensen, Holger
YR 2008
UL http://jnm.snmjournals.org/content/49/9/1537.abstract
AB 211At-labeled tumor-specific antibodies have long been considered for the treatment of disseminated cancer. However, the limited availability of the nuclide and the poor efficacy of labeling procedures at clinical activity levels present major obstacles to their use. This study evaluated a procedure for the direct astatination of antibodies for the production of clinical activity levels. Methods: The monoclonal antibody trastuzumab was conjugated with the reagent N-succinimidyl-3-(trimethylstannyl)benzoate, and the immunoconjugate was labeled with astatine. Before astatination of the conjugated antibody, the nuclide was activated with N-iodosuccinimide. The labeling reaction was evaluated in terms of reaction time, volume of reaction solvent, immunoconjugate concentration, and applied activity. The quality of the astatinated antibodies was determined by in vitro analysis and biodistribution studies in nude mice. Results: The reaction proceeded almost instantaneously, and the results indicated a low dependence on immunoconjugate concentration and applied activity. Radiochemical labeling yields were in the range of 68%−81%, and a specific radioactivity of up to 1 GBq/mg could be achieved. Stability and radiochemical purity were equal to or better than those attained with a conventional 2-step procedure. Dissociation constants for directly astatinated, conventionally astatinated, and radioiodinated trastuzumab were 1.0 ± 0.06 (mean ± SD), 0.44 ± 0.06, and 0.29 ± 0.02 nM, respectively. The tissue distribution in non–tumor-bearing nude mice revealed only minor differences in organ uptake relative to that obtained with the conventional method. Conclusion: The direct astatination procedure enables the high-yield production of astatinated antibodies with radioactivity in the amounts required for clinical applications.