Abstract
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Objectives A saturable phagocytosis is involved into most of intranodal retention mechanism of lymphatic imaging agent, and may lead to the unspecific uptake of higher echelon node. Scientific research reveals that germinal center in the cortex of lymph nodes contain intense mature B lymphocytes, overexpressing CD20 molecules. Our study will prove CD20 is an optimal specific target for sentinel lymph node (SLN) technique.
Methods Rituximab was labeled with technetium-99m or a near infrared dye, IRDye800CW. The target property was compared with radioclloid and 99mTc/IRDye800-HSA via biodistribution, lymphoscintigraphy imaging and NIR optical imaging in balb/c mice. After approved by Institutional Ethics Committee, 2000 breast cancer patients were performed 99mTc-rituximab-guided SLN imaging and biopsy. Histopathologic analysis of SLN was evaluated after biopsy.
Results 99mTc/IRDye800-rituximab showed high accumulation and sustained activity (4.49±0.43%) in SLN. Less than 0.1 %ID 99mTc/IRDye800-rituximab was detected in NSLN. The higher echelon node extractions were significantly higher for radiocolloid (3.87±0.37%) and slightly higher for 99mTc/IRDye800-HSA (0.53±0.12%) at 1 h. About 96.5% breast cancer patients were identified by 99mTc-rituximab lymphoscintigraphy. The SLN was identified in 96.5 % of patients when both blue dye and intraoperative gamma probe were used. The sensitivity and accuracy of SLNB were 96.8% and 98.8%. The specificity was 100%. The false negative rate was 3.3% and the negative predictive value was 98.1%. The positive predictive value was 100%. The locating mechanism was proved via immunohistochemical staining.
Conclusions Targeting CD20 is a new concept of SLN technique, and rituximab-based imaging agents are optimal agents for SLNB