Cargando…

Characterization and Stabilization of a New (64)Cu-Labeled Anti-EGFR Antibody NCAB001 for the Early Detection of Pancreatic Cancer with Positron Emission Tomography

Early diagnosis of pancreatic cancer using current imaging modalities remains challenging. We have developed a new approach to identify tumor lesions ≥ 3 mm in the pancreas by positron emission tomography (PET) with a new intraperitoneally administered (64)Cu-labeled anti-epidermal growth factor rec...

Descripción completa

Detalles Bibliográficos
Autores principales: Matsumoto, Hiroki, Igarashi, Chika, Tachibana, Tomoko, Hihara, Fukiko, Waki, Atsuo, Zhang, Ming-Rong, Yoshida, Sei, Naito, Kenichiro, Kurihara, Hiroaki, Ueno, Makoto, Ito, Kimiteru, Higashi, Tatsuya, Yoshii, Yukie
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8779674/
https://www.ncbi.nlm.nih.gov/pubmed/35056963
http://dx.doi.org/10.3390/pharmaceutics14010067
Descripción
Sumario:Early diagnosis of pancreatic cancer using current imaging modalities remains challenging. We have developed a new approach to identify tumor lesions ≥ 3 mm in the pancreas by positron emission tomography (PET) with a new intraperitoneally administered (64)Cu-labeled anti-epidermal growth factor receptor (EGFR) antibody (encoded as NCAB001), called (64)Cu-NCAB001 ipPET. Generally, in clinical research, a radiometal-antibody complex must be prepared immediately before use at the imaging site. To make (64)Cu-NCAB001 ipPET available to daily clinical practices in a sustainable way, the NCAB001-chelator conjugate and (64)Cu-NCAB001 must be characterized and stabilized. NCAB001 was manufactured under cGMP conditions. NCAB001 was conjugated with a bifunctional chelator (p-SCN-Bn-PCTA), and the antibody-chelator conjugate (PCTA-NCAB001) was characterized by LC/MS and ELISA. Thereafter, to effectively manufacture (64)Cu-NCAB001, we developed a new formulation to stabilize PCTA-NCAB001 and (64)Cu-NCAB001. An average of three PCTA chelators were conjugated per molecule of NCAB001. The relative binding potency of PCTA-NCAB001 was comparable to cetuximab. The formulation consisting of acetate buffer, glycine, and polysorbate-80 stabilized PCTA-NCAB001 for a year-long storage. Additionally, this formulation enabled the stabilization of (64)Cu-NCAB001 for up to 24 h after radiolabeling with a sufficient radioactivity concentration for clinical use. These results may accelerate the future use of (64)Cu-NCAB001 ipPET in clinical settings for the early diagnosis and treatment of pancreatic cancer.