Production and preclinical evaluation of 67ga-chx-a- adtpa-anti ror1 radioimmunoconjugate in a mouse moded l tpa-model of breast cancer

Receptor-tyrosine-kinase-like orphan receptor 1 (ROR1) is extensively expressed during embryogenesis but it is absent within most mature tissues. However, the expression of ROR1 has been reported inmultiple human malignancies including breast cancers. High-level expression of ROR1 in breast adenocarcinoma was associated with aggressive disease. So breast cancer radioimmunoscintigraphytargeting ROR1 expression is an attractive object in nuclear medicine researches. In this study, we evaluated the production, quality control and preclinical qualifications of a Gallium-67 labeled anti-ROR1 for PET imaging of breast cancer.Our previously produced monoclonal antibody against ROR1 was conjugated with p-NCS-Bn-CHX-A-DTPA bi-Functional linker and the purity of conjugatedproducts was assessed by Instant Thin Layer Chromatography (ITLC). In vitro cell binding studies were carried out in 4T1 cells which express ROR1 antigen. In the next step, the conjugated antibody wasradiolabeled with 67Ga and the tissue bio distribution of the radiolabeled antibody was evaluated in BALB/c mice bearing breast cancer at various time intervals using tissue counting and PET imagingscanner. The purity of immunoconjugate was approximately 88%. . The p-NCS-Bn-CHX-A-DTPA- anti-ROR1 showed immunoreactivity towards ROR1 antigen. Bio distribution and scintigraphy studiesshowed acceptable accumulation of the complex at the site of tumors compared to control group. The results showed that 67Ga-DTPA-anti-ROR1 may be considered as a potential PET tracer for diagnosisand follow-up of ROR1 expression in oncology

کلیدواژه ها:

Breast Cancer ، Cancer Diagnosis ، Solid Tumors ، Cancer Treatment and Management ، Radio-Oncology