Abstract
This study evaluated rituximab-conjugated, doxorubicin-loaded microbubbles (RDMs) in combination with ultrasound as molecular imaging agents for early diagnosis of B cell lymphomas, and as a targeted drug delivery system. Rituximab, a monoclonal CD20 antibody, was attached to the surfaces of doxorubicin-loaded microbubbles. RDM binding to B cell lymphoma cells was assessed using immunofluorescence. The cytotoxic effects of RDMs in combination with ultrasound (RDMs+US) were evaluated in vitro in CD20+ and CD20– cell lines, and its antitumor activities were assessed in Raji (CD20+) and Jurkat (CD20–) lymphoma cell-grafted mice. RDMs specifically bound to CD20+ cells in vitro and in vivo. Contrast enhancement was monitored in vivo via ultrasound. RDM peak intensities and contrast enhancement durations were higher in Raji than in Jurkat cell-grafted mice (P<0.05). RDMs+US treatment resulted in improved antitumor effects and reduced systemic toxicity in Raji cell-grafted mice compared with other treatments (P<0.05). Our results showed that RDMs+US enhanced tumor targeting, reduced systemic toxicity, and inhibited CD20+ B cell lymphoma growth in vivo. Targeted RDMs could be employed as ultrasound molecular imaging agents for early diagnosis, and are an effective targeted drug delivery system in combination with ultrasound for CD20+ B cell malignancy treatment.
Highlights
IntroductionUltrasound (US) molecular imaging is a novel diagnostic approach for early detection of nonhodgkin lymphoma
Diagnosis is pivotal for therapeutic success in many types of cancers
RDM morphologies and size distributions were observed via scanning electron microscopy (SEM) (Figure 2A) and transmission electron microscopy (TEM) (Figure 2B), respectively
Summary
Ultrasound (US) molecular imaging is a novel diagnostic approach for early detection of nonhodgkin lymphoma. Recent studies suggest that targeted microbubbles as US contrast agents (TMUCA) may serve as probes for US molecular imaging. TMUCAs can accumulate and remain at the tumor site for long time periods, and imaging at the molecular level can be acquired using US after TMUCA venous injection [1,2,3]. Various types of TMUCA have been applied for cell-specific targeting with US molecular imaging in vivo [5,6,7,8,9,10], to assess intravascular inflammation, intravascular thrombosis and tumor blood vessels. TMUCA diameters were adjusted to approximately 500 nm for easy passage through vascular endothelial cells and improved molecular imaging
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