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The aim of this study was to evaluate the value of ultrasound molecular imaging with nanobubbles targeted to T lymphocytes in detection of acute cellular rejection in heart transplantation.
Lipid nanobubbles bearing anti-CD3 antibody(NBCD3) or isotype control antibody(NBcon) were prepared and characterized. Binding specificity of the NBCD3 to T lymphocytes was demonstrated by optical and confocal laser scanning microscope in vitro. Ultrasound molecular imaging with NBCD3 and NBcon were performed with a commercial ultrasound system IU22 (Philips Medical Systems, Amsterdam, the Netherlands) using a L12-5 linear array transducer five days after heart transplantation. We used the destruction-replenishment method to detect the signal from attached nanobubbles. Immunohistochemical staining was used to detect the infiltration of T lymphocytes.
There was significant adhesion of NBCD3 to T lymphocytes compared with NBcon in vitro. The contrast intensity of adherent NBCD3 was significantly higher than NBcon in allograft rats (2.86 ± 2.05 dB versus 0.51 ± 0.31 dB, P<0.01). However, there was no statistically significant difference for NBCD3 and NBcon in isograft rats (0.83 ± 0.47 dB versus 0.74 ± 0.50 dB, P>0.05). Immunohistochemistry examination of the myocardium confirmed T lymphocytes infiltration in allografts and the signal of attached NBCD3 was positively correlated with the numbers of T lymphocytes (R2 = 0.67, P<0.01).
Ultrasound molecular imaging with T lymphocytes targeted nanobubbles allows noninvasive evaluation of acute cardiac transplantation rejection.