Synthesis and Feasibility Evaluation of a new Trastuzumab Conjugate Integrated with Paclitaxel and ⁸⁹Zr for Theranostic Application Against HER2‐Expressing Breast Cancers

Abstract

The preparation and in vitro evaluation of a theranostic conjugate composed of trastuzumab, paclitaxel (PTX), and deferoxamine (DFO)‐chelated 89Zr have been reported. These comounds have potential applications against HER2 receptor positive breast cancers. We conjugated DFO and PTX to trastuzumab by exploiting simple conjugation chemistry. The conjugate (DFO‐trastuzumab‐PTX) showed excellent radiolabeling efficiency with 89Zr and the labeled conjugate had high in vitro stability in human serum. Furthermore, DFO‐trastuzumab‐PTX displayed comparable cytotoxicity with PTX and 89Zr‐DFO‐trastuzumab‐PTX exhibited HER2 receptor‐mediated binding on HER2‐positive MDA‐MB‐231 breast cancer cells. The results of our in vitro study indicate high potential of 89Zr‐DFO‐trastuzumab‐PTX to be utilized in the theranostic application against HER2‐postive breast cancers.

Perspective of Fibrin Capsule in Inhibition of Growth and Metastasis of Malignant Tumors

“…similar to the attachment of the MCC-DM1 molecule to the Trastuzumab-emtansine structure [37,38]. The peptide bound is formed between the free amino group of trastuzumab and the carboxyl group of the fibrinogen molecule.…”

“…Пропонуємо здійснити приєднання молекули фібриногену до трастузумабу через утворення пептидного зв'язку аналогічно до приєднання молекули МСС-DM1 у структуру Трастузумаб-емтанзину [37,38]. Пептидний зв'язок утвориться між вільною аміногрупою трастузумабу й карбоксильною групою молекули фібриногену.…”

Actively Targeted Nanomedicines in Breast Cancer: From Pre-Clinal Investigation to Clinic

“…This formulation was efficiently internalized by HER-2-overexpressing breast cancer cells (SK-BR3 cells) and was barely taken up by HER-2-negative cells, also exerting an anticancer activity that was slightly higher than free paclitaxel. This indicates that this ADC may be a promising theragnostic tool for HER-2-positive tumors [ 95 ]. Trastuzumab–cisplatin conjugates have also been prepared, showing similar effects.…”

Immüno-PET İçin Geliştirilen Zirkonyum-89 (89Zr) Radyofarmasötikleri

“…89 Zr-DFO-Trastuzumab-PTX (Paklitaksel) konjugatı HER2(+) meme kanser hücreleri üzerinde değerlendirilmişdir. Bu radyokonjugatın terapötik uygulamalarda kullanım potansiyelinin yüksek olduğu gösterilmişdir [37]. Klinik çalışamalara baktığımızda; 89 Zr-trastuzumabın tümör tutulumunın HER2(+) 34 ve HER2(-) 16 kadın hastanın meme kanserini ayırt edip edemeyeceğini değerlendirilmişdir.…”