Vaidyanathan, G., Affleck, D.J., Bigner, D.D. & Zalutsky, M.R. N-succinimidyl 3-[211At]astato-4-guanidinomethylbenzoate: an acylation agent for labeling internalizing antibodies with alpha-particle emitting 211At. Nucl. Med. Biol. 30, 351-359

Department of Biomedical Engineering (BME), Duke University, Durham, North Carolina, United States
Nuclear Medicine and Biology (Impact Factor: 2.41). 06/2003; 30(4):351-9. DOI: 10.1016/S0969-8051(03)00005-2
Source: PubMed


The objective of this study was to develop a method for labeling internalizing monoclonal antibodies (mAbs) such as those reactive to the anti-epidermal growth factor receptor variant III (EGFRvIII) with the alpha-particle emitting radionuclide (211)At. Based on previous work utilizing the guanidine-containing acylation agent, N-succinimidyl 4-guanidinomethyl-3-[(131)I]iodobenzoate ([(131)I]SGMIB), we have now investigated the potential utility of its astato analogue for labeling the anti-EGFRvIII mAb L8A4. N-succinimidyl 3-[(211)At]astato-4-guanidinomethylbenzoate ([(211)At]SAGMB) in its Boc-protected form was prepared from a tin precursor in 61.7 +/- 13.1% radiochemical yield, in situ deprotected to [(211)At]SAGMB, which was coupled to L8A4 in 36.1 +/- 1.9% yield. Paired-label internalization assays demonstrated that tumor cell retention of radioactivity for L8A4 labeled using [(211)At]SAGMB was almost identical to L8A4 labeled using [(131)I]SGMIB, and 3-4-fold higher than for mAb radioiodinated using Iodogen. Paired-label biodistribution of L8A4 labeled using [(211)At]SAGMB and [(131)I]SGMIB in athymic mice hosting U87MGdeltaEGFR xenografts resulted in identical uptake of both (211)At and (131)I in tumor tissues over 24 h. Although higher levels of (211)At compared with (131)I were sometimes seen in tissues known to sequester free astatide, these (211)At/(131)I uptake ratios were considerably lower than those seen with other labeling methods. These results suggest that [(211)At]SAGMB may be a useful acylation agent for labeling internalizing mAbs with (211)At.

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Available from: Michael Zalutsky, Nov 05, 2015
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    • "different ways (Wilbur et al., 2007; Pruszynski et al., 2006, 2008; Vaidyanathan et al., 2003). Coupling a stannylated aromatic succinimide ester, MeATE reagent, via N-acylation reactions with lysine on the biomolecule, followed or preceded by an electrophilic aromatic substitution of Sn(CH 3 ) 3 with 211 At is, although, the most common method (Zalutsky and Narula, 1988; Lindegren et al., 2008). "
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    ABSTRACT: In this work a new coupling reagent, N-[2-(maleimido)ethyl]-3-(trimethylstannyl)benzamide, for radiohalogenation has been synthesized and characterized. The reagent is intended to either be attached to reduced disulfide bridges of proteins (making the halogenation site-specific) or to free terminal cysteine groups on peptides. The new reagent was also shown to be easily halogenated with inactive bromine and iodine as well as (125)I and (211)At, indicating potential use within targeted radiotherapy. Copyright © 2014 Elsevier Ltd. All rights reserved.
    Full-text · Article · Nov 2014 · Applied Radiation and Isotopes
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    • "considered. Indirect radiolabeling mainly uses the electrophilic substitution of leaving groups attached to vinylic [8] or aromatic backbones [9] [10] [11] with At(+ I). Accordingly, succinimidyl astatobenzoate (SAB), which is currently the most frequently used for proteins labeling with astatine-211, is synthesized from the halodemetalation of a stannylated aromatic precursor [12]. "
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    • "We have developed a template for the radiohalogenation of mAbs that undergo receptor-mediated internalization and mAbs labeled with this reagent have shown encouraging enhancement of tumor radioactivity residence time [27] [28] [29]. Because octreotide derivatives also undergo receptor-mediated internalization, our objective was to develop an octreotate conjugate comprising this template. "
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