ارزيابي جذب توموري قطعه F(abʹ) 2 آنتي بادي مونوكلونال PR 81 نشاندار شده با 99mTc در مدل موشي مبتلا به سرطان پستان

Evaluation of tumor targeting with 99mTc labeled F(abʹ)2 fragment of PR81 in mouse model bearing breast tumor

Compared to intact IgG, F(abʹ)2 exhibit significantly improved tumor specificity and intratumor penetration in animal models. Generally, lower molecular-weight agents provide better target to non-target ratios due to their rapid background clearance. The goal of this study is the enzyme digestion of PR81 and labeling of prepared F(abʹ)2 fragments with 99mTc in order to produce a biologic radiopharmaceutical for radioim-munoscintigraphy of breast cancer. So antibody PR81 was digested with pepsin for 28 hours at 37°C. The F(abʹ)2 fragments were purified by protein A column chromatography. The purity of F(abʹ)2 fragments was evaluated by SDS-PAGE and proved to be more than 95%. The immunoreactivity of the complex assessed by radioimmunoassay was determined to be 65.2%±5.1. Radiolabeling of F(abʹ)2 fragment using the HYNIC as a chelator and tricine as a co-ligand was resulted to special activity of 70.1%±5.2. The in vitro stability of labeled product checked in human serum by gel filtration chromatography (FPLC) was 55.2%±5.3. Biodistribution studies in BALB/c mice with breast tumor xenograft after 4, 8 and 24hs following to the preparation injection, demonstrated a specific localization of the compound at the site of tumors 4hs post injection with high sensitivity and minimum accumulation in non-target organs.