In vivo magnetomotive optical molecular imaging using targeted magnetic nanoprobes

Abstract

Dynamic magnetomotion of magnetic nanoparticles (MNPs) detected with magnetomotive optical coherence tomography (MM-OCT) represents a new methodology for contrast enhancement and therapeutic interventions in molecular imaging. In this study, we demonstrate in vivo imaging of dynamic functionalized iron oxide MNPs using MM-OCT in a preclinical mammary tumor model. Using targeted MNPs, in vivo MM-OCT images exhibit strong magnetomotive signals in mammary tumor, and no significant signals were measured from tumors of rats injected with nontargeted MNPs or saline. The results of in vivo MM-OCT are validated by MRI, ex vivo MM-OCT, Prussian blue staining of histological sections, and immunohistochemical analysis of excised tumors and internal organs. The MNPs are antibody functionalized to target the human epidermal growth factor receptor 2 ( HER2 neu ) protein. Fc-directed conjugation of the antibody to the MNPs aids in reducing uptake by macrophages in the reticulo-endothelial system, thereby increasing the circulation time in the blood. These engineered magnetic nanoprobes have multifunctional capabilities enabling them to be used as dynamic contrast agents in MM-OCT and MRI.

Selective treatment and monitoring of disseminated cancer micrometastases in vivo using dual-function, activatable immunoconjugates

“…Microendoscopy has taken microscopy to new depths in vivo using miniaturized optics (46), and this technology is emerging for "optical biopsy" of cancer (32,(47)(48)(49)(50)(51)(52)(53). Through the development of in vivo fluorescence microendoscopy with activatable immunoconjugates and automated image analysis algorithms (Fig.…”

Dual-coil magnetomotive optical coherence tomography for contrast enhancement in liquids

“…Magnetic particles can be functionalized to target specific cellular receptors or pathology, and the magnetomotive response can then be utilized to localize the presence of these particles. For instance, tumor detection with MM-OCT in conjunction with HER-2/neu-targeted MNPs was successfully demonstrated in an in vivo rat mammary tumor model [7]. In another study, thrombi consisting of MNP-labeled platelets in ex vivo porcine arteries were successfully detected with MM-OCT [8].…”

“…3(M)) can be affected by spatial frequency components (e.g., heartbeat, pulsation of blood vessels, muscle twitching, etc.). A number of approaches, such as spatially oversampling the image or comparing the B-field OFF scan with the B-field ON scan, can be used to ensure that the spatial frequencies due to the sample structure do not overlap with the modulation frequency [4][5][6][7][8]18].…”

“…Figure 2 shows the conceptual structure and transmission electron microscopy (TEM) images of the magnetic protein-shell, oil-core, microspheres used in this study. These particular contrast agents are being developed as blood-pool drug-delivery agents for targeting cardiovascular disease and angiogenesis in cancer [4,[6][7][8]. In general, these magnetic microspheres consist of a hydrophobic core (e.g., vegetable oil or drug) and a hydrophilic shell (i.e., bovine serum albumin).…”

“…The theory of AC magnetic modulation was investigated previously by Oldenburg, et al [4][5][6][7]. Briefly, the magnetomotive force (F MNP ) on a single MNP can be written as the following:…”