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|Title:||A Radiolabeled Fully Human Antibody to Human Aspartyl (Asparaginyl) β-Hydroxylase Is a Promising Agent for Imaging and Therapy of Metastatic Breast Cancer|
|Authors:||Revskaya Ekaterina; JIANG Z.; MORGENSTERN Alfred; BRUCHERTSEIFER Frank; SESAY M; WALKER S; FULLER S; LEBOWITZ Ms; GRAVEKAMP C; GHANBARI Ha; DADACHOVA E.|
|Citation:||CANCER BIOTHERAPY AND RADIOPHARMACEUTICALS vol. 32 no. 2 p. 57-65|
|Publisher:||MARY ANN LIEBERT|
|Type:||Articles in periodicals and books|
|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) b-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 HAAHspecific 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. The 111In-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 with 213Bi—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.|
|JRC Directorate:||Nuclear Safety and Security|
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