NIR-II aza-BODIPY Platform for the Development of a Fluorescent Antibody Drug Conjugate
- Real-time imaging of antibody-drug conjugates (ADCs) offers valuable insights for assessing tumor targeting specificity, monitoring therapeutic efficacy, and detecting off-target accumulation that may cause adverse effects. To enable precise tracking, we developed a versatile fluorescent platform based on an NIR-II emitting aza-BODIPY dye, which can be site-specifically grafted onto an IgG1 antibody to generate well-defined fluorescent ADCs. As a proof of concept, we synthesized an HER2-targeting trastuzumab immunoconjugate bearing a NIR-II aza-BODIPY fluorophore. The cytotoxic monomethyl auristatin E (MMAE) payload was introduced in the final step, resulting in a trackable and homogeneous ADC suitable for both in vitro and in vivo investigations. The resulting Trastu-azaNIRII-MMAE selectively accumulated in HER2-positive subcutaneous tumors, significantly reducing the tumor growth. Using NIR-II optical imaging, a single injection of the NIR-II-ADC allowed for the detection of theReal-time imaging of antibody-drug conjugates (ADCs) offers valuable insights for assessing tumor targeting specificity, monitoring therapeutic efficacy, and detecting off-target accumulation that may cause adverse effects. To enable precise tracking, we developed a versatile fluorescent platform based on an NIR-II emitting aza-BODIPY dye, which can be site-specifically grafted onto an IgG1 antibody to generate well-defined fluorescent ADCs. As a proof of concept, we synthesized an HER2-targeting trastuzumab immunoconjugate bearing a NIR-II aza-BODIPY fluorophore. The cytotoxic monomethyl auristatin E (MMAE) payload was introduced in the final step, resulting in a trackable and homogeneous ADC suitable for both in vitro and in vivo investigations. The resulting Trastu-azaNIRII-MMAE selectively accumulated in HER2-positive subcutaneous tumors, significantly reducing the tumor growth. Using NIR-II optical imaging, a single injection of the NIR-II-ADC allowed for the detection of the conjugate over a period of more than one month, highlighting its potential for long-term tracking and therapeutic applications.…


| Autor*innen: | E. Chazeau, A. Pipier, Karl David WegnerORCiD, F. Ghiringhelli, L. Sancey, C. Paul, C. Goze |
|---|---|
| Dokumenttyp: | Zeitschriftenartikel |
| Veröffentlichungsform: | Verlagsliteratur |
| Sprache: | Englisch |
| Titel des übergeordneten Werkes (Englisch): | Journal of Medicinal Chemistry |
| Jahr der Erstveröffentlichung: | 2025 |
| Organisationseinheit der BAM: | 1 Analytische Chemie; Referenzmaterialien |
| 1 Analytische Chemie; Referenzmaterialien / 1.2 Biophotonik | |
| Veröffentlichende Institution: | Bundesanstalt für Materialforschung und -prüfung (BAM) |
| Verlag: | ACS Publications |
| Jahrgang/Band: | 68 |
| Ausgabe/Heft: | 7 |
| Erste Seite: | 7232 |
| Letzte Seite: | 7242 |
| DDC-Klassifikation: | Naturwissenschaften und Mathematik / Chemie / Analytische Chemie |
| Technik, Medizin, angewandte Wissenschaften / Ingenieurwissenschaften / Sanitär- und Kommunaltechnik; Umwelttechnik | |
| Freie Schlagwörter: | Antibody drug conjugate; Fluorescence; In vivo imaging; NIR-II; Quality assurance |
| Themenfelder/Aktivitätsfelder der BAM: | Chemie und Prozesstechnik |
| Chemie und Prozesstechnik / Chemische Charakterisierung und Spurenanalytik | |
| Umwelt | |
| DOI: | 10.1021/acs.jmedchem.4c02777 |
| Verfügbarkeit des Dokuments: | Datei im Netzwerk der BAM verfügbar ("Closed Access") |
| Datum der Freischaltung: | 05.05.2025 |
| Referierte Publikation: | Ja |
| Datum der Eintragung als referierte Publikation: | 05.05.2025 |

