title: A Radiolabeled Fully Human Antibody to Human Aspartyl (Asparaginyl) β-Hydroxylase Is a Promising Agent for Imaging and Therapy of Metastatic Breast Cancer.
abstract: There is a need for novel effective and safe therapies for metastatic breast cancer based on targeting tumor-specific molecular markers of cancer. Human aspartyl (asparaginyl) β-hydroxylase (HAAH) is a highly conserved enzyme that hydroxylates epidermal growth factor-like domains in transformation-associated proteins and is overexpressed in a variety of cancers, including breast cancer. A fully human monoclonal antibody (mAb) PAN-622 has been developed to HAAH. In this study, they describe the development of PAN-622 mAb as an agent for imaging and radioimmunotherapy of metastatic breast cancer. PAN-622 was conjugated to several ligands such as DOTA, CHXA″, and DTPA to enable subsequent radiolabeling and its immunoreactivity was evaluated by an HAAH-specific enzyme-linked immunosorbent assay and binding to the HAAH-positive cells. As a result, DTPA-PAN-622 was chosen to investigate biodistribution in healthy CD-1 female mice and 4T1 mammary tumor-bearing BALB/c mice. The111In-DTPA-pan622 mAb concentrated in the primary tumors and to some degree in lung metastases as shown by SPECT/CT and Cherenkov imaging. A pilot therapy study with213Bi-DTPA-PAN-622 demonstrated a significant effect on the primary tumor. The authors concluded that human mAb PAN-622 to HAAH is a promising reagent for development of imaging and possible therapeutic agents for the treatment of metastatic breast cancer.
authors.affiliation: 1 Department of Radiology, Albert Einstein College of Medicine , Bronx, New York.
authors.forename: Ekaterina
authors.initials: E
authors.lastname: Revskaya
authors.affiliation: 1 Department of Radiology, Albert Einstein College of Medicine , Bronx, New York.
authors.forename: Zewei
authors.initials: Z
authors.lastname: Jiang
authors.affiliation: 2 European Commission, Joint Research Centre , Directorate for Nuclear Safety and Security, Karlsruhe, Germany .
authors.forename: Alfred
authors.initials: A
authors.lastname: Morgenstern
authors.affiliation: 2 European Commission, Joint Research Centre , Directorate for Nuclear Safety and Security, Karlsruhe, Germany .
authors.forename: Frank
authors.initials: F
authors.lastname: Bruchertseifer
authors.affiliation: 3 Goodwin Biotechnology , Plantation, Florida.
authors.forename: Muctarr
authors.initials: M
authors.lastname: Sesay
authors.affiliation: 4 Panacea Pharmaceuticals , Gaithersburg, Maryland.
authors.forename: Susan
authors.initials: S
authors.lastname: Walker
authors.affiliation: 4 Panacea Pharmaceuticals , Gaithersburg, Maryland.
authors.forename: Steven
authors.initials: S
authors.lastname: Fuller
authors.affiliation: 4 Panacea Pharmaceuticals , Gaithersburg, Maryland.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Lebowitz
authors.affiliation: 1 Department of Radiology, Albert Einstein College of Medicine , Bronx, New York.
authors.forename: Claudia
authors.initials: C
authors.lastname: Gravekamp
authors.affiliation: 4 Panacea Pharmaceuticals , Gaithersburg, Maryland.
authors.forename: Hossein A
authors.initials: HA
authors.lastname: Ghanbari
authors.affiliation: 1 Department of Radiology, Albert Einstein College of Medicine , Bronx, New York.
authors.forename: Ekaterina
authors.initials: E
authors.lastname: Dadachova
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry*; D001943:Breast Neoplasms / Q000000981:diagnostic imaging* / Q000188:drug therapy* / Q000532:radiotherapy; D045744:Cell Line, Tumor; D003952:Diagnostic Imaging / Q000379:methods; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008024:Ligands; D051379:Mice; D008807:Mice, Inbred BALB C; D006899:Mixed Function Oxygenases / Q000737:chemistry*; D009362:Neoplasm Metastasis; D016499:Radioimmunotherapy / Q000379:methods; D014018:Tissue Distribution
chemical_list: D000911:Antibodies, Monoclonal; D008024:Ligands; D006899:Mixed Function Oxygenases; C058291:aspartic acid 2-oxoglutarate-dependent dioxygenase
keywords: 111In; 213Bi; HAAH; PAN-622 human antibody; metastatic breast cancer; radioimmunotherapy