In vivo cellular imaging of HER2-overexpressing breast tumor cells through electron paramagnetic resonance (EPR)

Due to recent advances in electron paramagnetic resonance imaging (EPRI) technology, in vivo localization of a single tissue based on unique physiology, has become a real possibility. EPRI could be a powerful imaging modality to define tumor boundaries, detect metastatic lesions, and report tissue-specific physiological information. The Human Epidermal Growth Factor Receptor 2 (HER2) is overexpressed in ∼25-30% of breast tumors. HER2-overexpressing breast tumors exhibit increased proliferation and metastasis, and subsequently, poor clinical prognosis. Presented here, is a novel mechanism for selective delivery of molecular EPRI probes to HER2-overexpressing breast tumor cells. We demonstrate bio-compatibility of EPRI probes we previously developed, and that encapsulation of these probes in liposomes allows cellular accumulation of EPR signal through endocytosis. Encapsulating nitroxides in anti-HER2 immunoliposomes, designed for targeted delivery to cells expressing the HER2 receptor, permits high levels of tissue-specific probe accumulation in breast tumor cells overexpressing HER2 in vitro. We demonstrate that nitroxide-loaded immunoliposomes can be optimized for in vivo applications, and through the use of tumor-bearing animals, provide evidence for the feasibility of targeting HER2-overexpressing tumors in vivo