Rituximab-conjugated, doxorubicin-loaded microbubbles as a theranostic modality in B-cell lymphoma

// Shoubing Zhou 1 , Xiu Zhang 1 , Cailian Wang 1 1 Department of Oncology, Zhongda Hospital, Medical School of Southeast University, Nanjing, Jiangsu 210009, P.R. China Correspondence to: Cailian Wang, email: wangcailianseu@yahoo.com Keywords: Rituximab, microbubble, ultrasound, theranostics, B cell lymphoma Received: June 29, 2016     Accepted: November 7, 2016     Published: November 25, 2016 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.