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| Verfasst von: | Eisenhut, Michael [VerfasserIn]  |
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| | Lehmann, Wolf-Dieter [VerfasserIn] |
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| | Becker, W. [VerfasserIn] |
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| | Behr, T. [VerfasserIn] |
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| | Elser, Hubert [VerfasserIn] |
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| | Strittmatter, W. [VerfasserIn] |
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| | Steinsträsser, A. [VerfasserIn] |
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| | Baum, Richard P. [VerfasserIn] |
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| | Valerius, Thomas [VerfasserIn] |
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| | Repp, Roland [VerfasserIn] |
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| | Deo, Yashwant M. [VerfasserIn] |
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| Titel: | Bifunctional NHS-BAT ester for antibody conjugation and stable technetium-99m labeling |
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| Titelzusatz: | conjugation chemistry, immunoreactivity and kit formulation |
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| Verf.angabe: | M. Eisenhut, W.D. Lehmann, W. Becker, T. Behr, H. Elser, W. Strittmatter, A. Steinsträsser, R.P. Baum, T. Valerius, R. Repp, Y. Deo |
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| E-Jahr: | 1996 |
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| Jahr: | February 1, 1996 |
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| Umfang: | 9 S. |
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| Fussnoten: | Gesehen am 05.12.2024 |
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| Titel Quelle: | Enthalten in: Journal of nuclear medicine |
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| Ort Quelle: | New York, NY : Soc., 1964 |
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| Jahr Quelle: | 1996 |
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| Band/Heft Quelle: | 37(1996), 2, Seite 362-370 |
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| ISSN Quelle: | 2159-662X |
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| | 1535-5667 |
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| Abstract: | <p>Conjugation chemistry and kit formulated binding of the NHS ester of 6-(4′-(4″-carboxyphenoxy)buty9-2, 10-dimercapto-2,10-dimethyl-4,8-diazaundecane (NHS-BAT ester) to monoclonal antibodies (MAbs) was investigated. The functionalities of the resulting BAT conjugated and <sup>99m</sup>Tc-labeled MAbs BW 431/26, MAb 425 and bispecific MDX210 (fragment construct) were tested by immunoreactivity and immunoscintigraphy. <b>Methods:</b> The kinetics and chemistry of the conjugation reaction were monitored by high-performance liquid chromatography, size-exclusion chromatography and positive fast-atom-bombardment mass spectra (FAB-MS). The <sup>99m</sup>Tc BAT-MAbs were tested with various immunoreactivity as says. The biodistribution of <sup>99m</sup>Tc-BAT-BW 431/26 in rats was compared with directly labeled BW 431/26. <b>Results:</b> At pH 8.5 and 25°C,the reactivity of the NHS-BAT ester was high with 90% completion after 30 min. The conjugation yield of 19 μM MAb and 228 μM NHS-BAT ester amounted to 30%. Higher NHS-BAT ester concentrations afforded higher BAT-to-MAb ratios. According to FAB-MS, the conjugation competing hydrolysis surprisingly occurred at the NHS ring. Almost quantitative <sup>99m</sup>Tc labeling was achieved after 5 min at 25°C. Immunoreactivity of the <sup>99m</sup>Tc-BAT antibodies showed >90% recovery and proved to be insensitive to BAT-to-MAb ratios of up to 10. The <sup>99m</sup>Tc-BAT-BW 431/26 showed similar organ distribution but revealed less urinary excretion compared with the directly labeled BW 431/26. Immunoscintigraphy with <sup>99m</sup>Tc-labeled and BAT-BW 431/26 and BAT-MAb 425 showed the respective biological function in vivo. <b>Conclusion:</b> According to straightforward conjugation chemistry, the ease of <sup>99m</sup>Tc labeling and the application of a simple ultrafiltration technique, the NHS BAT ester represents a nondestructive, universally applicable bifunctional ligand to introduce stable <sup>99m</sup>Tc protein binding sites. Kit formulated conjugation/labeling can be performed with little time requirements and laboratory experience.</p> |
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| URL: | Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.
Volltext: https://jnm.snmjournals.org/content/37/2/362 |
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| Datenträger: | Online-Ressource |
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| Sprache: | eng |
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| K10plus-PPN: | 1910916994 |
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| Verknüpfungen: | → Zeitschrift |
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Bifunctional NHS-BAT ester for antibody conjugation and stable technetium-99m labeling / Eisenhut, Michael [VerfasserIn]; February 1, 1996 (Online-Ressource)
