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Objective: Estrogen receptor is a member of the nuclear hormone family of intracellular receptors;divided into two different forms estrogen α and estrogen β.Estrogen receptor α36 (ER-α36) is a novel variant of estrogen receptor α which associates with estrogen receptor positive tumors.109was a novel expressed monoclonal antibody, which shown high affinity to ER-α36.In this study,technetium-99m labeled 109 was investigated as a novel imaging probe for breast cancer.Methods: 109 was labeled with Tc-99m using glucoheptonate (GH) as exchange chelator, after reduced by 2-mercaptoethanol.99mTc-109 was purified by PD-10 column and detected using both HPLC and ITLC.The biodistribution study was carried out in breast cancer beating nude mice,and the imaging study was performed on the nude mice at specific time point.Results: The labeling efficiency was between 80 to 85%.The radiochemical purity was up to 95%after purification.In biodistribution study, 99mTc-109 showed high tumor affinity (%ID) and was cleared from normal tissues quickly.According to the pharmacokinetic results, the half-life of the radiolabelled antibody was shorter than normal biological macromolecules, t1/2α=0.2143h, and t1/2β=3.932h.The biodistribution study shows the tracer was mainly metabolized through kidney and liver.No free Tc-99m was observed within 24h.Ideal tumor imaging was obtained at 24h, and the ratio of tumor to muscle was up to 4.Conclusions: Antibody 109 was successfully labeled by technetium-99m with high labeling efficiency and radiochemical purity.The antibody remained its biological activity after radiolabeling procedure.High ratio of target/non-target result was observed within 24h.99mTc-109 showed good bioactivity and pharmacokinetics.All these results indicate 99mTc-109 is a valuable tumor probe for estrogen receptor targeting and a potential agent for breast cancer imaging in clinical practice.