Tumor-targeted enzyme mediated MR signal amplification using paramagnetic substrates.
Bogdanov A, Kang H, Querol M, Bennett D, Sotak C, Yudina A, Verel I
UMASS Medical School
A novel combination of a pre-targeting system of cancer-specific antibody-enzyme conjugates and a paramagnetic substrate has been designed for tumor-specific receptor MR imaging. Monoclonal antibody conjugates linked to horseradish peroxidase (HRP) or glucose oxidase (GO) were synthesized by using bisaromatic hydrazone bonds. Purified conjugates were tested in vitro and in vivo using human squamous carcinoma model in the presence of bis-(5-hydroxytrypatmide)-DTPA(Gd) paramagnetic HRP substrate (5HT-DTPAGd). L6 (anti-L6 protein family, a pan-carcinoma specific monoclonal antibody, mAb) was tested for tumor cell pre-targeting and showed strong and specific regional tumor T1 signal enhancement on MRI after the injection of 0.2-0.25 mmol dose of 5HT-DTPAGd/kg.