Evaluation of 99mTc-glucarate as a breast cancer imaging agent in a xenograft animal model

IntroductionThe use of [99mTc]glucarate has been reported as an infarct-avid agent with the potential for very early detection of myocardial infarction. [99mTc]Glucarate has also been postulated as an agent for non-invasive detection of tumors. The aim of our study was to develop a Glucarate kit and evaluate [99mTc]glucarate as a potential cancer imaging agent in female SCID mice bearing human MDA-MB-435 breast tumors.MethodsGlucarate in a kit formulation was labeled with 99mTc and evaluated for radiolabelling efficiency and radiochemical purity. The Glucarate kit stability was assessed by monthly quality controls. The pharmacokinetics of [99mTc]glucarate were determined in female SCID mice bearing MDA-MB-435 human breast carcinoma tumors at 0.5, 1, 2, 4 and 24 h. Nuclear imaging studies were performed with a micro-single photon emission tomography (SPECT)/computed tomography (CT) system at 2 h post injection, while magnetic resonance imaging (MRI) was employed for tumor morphology analysis and metastatic deposit localization.ResultsThe Glucarate kits exhibited a stable shelf life of 6 months. [99mTc]Glucarate was obtained with radiochemical purity greater than 95%. Biodistribution studies demonstrated moderate tumor uptake coupled with high renal clearance. Tumor-to-muscle ratios were 4.85 and 5.14 at 1 and 4 h post injection. MRI analysis showed tumors with dense cellular growth and moderate central necrosis. [99mTc]Glucarate uptake in the primary MDA-MB-435 shoulder tumors and metastatic lesions were clearly visualized with micro-SPECT/CT imaging.ConclusionsSelective tumor uptake and rapid clearance from nontarget organs makes [99mTc]glucarate a potential agent for breast cancer imaging that awaits validation in a clinical trial.