[Interleukin-2 improves the antitumor activity of Rituximab in patients with B-cell lymphoma in vitro].

OBJECTIVE: To establish a method to predict therapeutic effect of Rituximab and explore the feasibility and potential of IL-2 improving antitumor activity of Rituximab with upregulated antibody-dependent cellular cytotoxicity (ADCC) in patients with B-cell lymphoma. METHODS: Eighteen B-cell lymphoma patients and 13 health volunteers entered the study. Peripheral blood mononuclear cells (PBMNC) were isolated as effector cells, and Daudi (Burkitt's lymphoma) cells as target cell, the cytotoxicity and ADCC mediated by Rituximab (10 microg/ml) of PBMNC at different E:T ratios were performed by standard 51Cr-release-assay in vitro with or without IL-2-activation. Flow cytometric analysis was performed to identify PBMNC phenotype with or without IL-2-activation. RESULTS: A marked decrease of cytotoxicity and Rituximab mediated ADCC in the patients as compared with that in health volunteers, the results being (5.80 +/- 1.16)%, (14.32 +/- 1.50)% and (14.29 +/- 1.68)%, (24.14 +/- 1.53)% (t = 3.693, P = 0.001 and t = 3.372, P = 0.003) respectively. The decrease was correlated with the therapeutic effect of Rituximab (r = 0.781, P < 0.05). The cytotoxicity and Rituximab mediated ADCC in the patients could be partly recovered after IL-2 activation from (5.80 +/- 1.16)%, (14.32 +/- 1.50)% to (15.43 +/- 2.62)%, (35.79 +/- 2.58)% (t = 3.35, P = 0.003 and t = 7.17, P < 0.001) respectively. CONCLUSIONS: It may be a useful method for predicting the effect of Rituximab in B-cell lymphoma patients to analyze the cytotoxicity and ADCC of their PBMNC. The impaired activity of PBMNC could be partly recovered when IL-2 was administered before the use of Rituximab.

[Preliminary study on a new sentinel lymphoscintigraphy agent 99mTc-Rituximab for breast patient].

OBJECTIVE: To develop a new imaging agent, (99m)Tc-Rituximab, for sentinel lymphoscinti-graphy and investigate its feasibility in detecting the sentinel lymph node (SLN) for breast cancer patient. METHODS: (99m)Tc-Rituximab was prepared by introducing (99m)Tc directly into the mclecule of Rituximab, thus a new kind of lymphoscintigraphy agent ((99m)Tc-Rituximab) was produced. Five Bal b/c mice and ten breast cancer patients underwent dynamic SLN mapping procedures using (99m)Tc-Rituximab. Axillary lymph node status in breast cancer patients were evaluated with the fusion images, which was processed by computer software. With ROI technique, SLN/background ratio and the rate of SLN uptake were calculated and the dynamic curve of SLN uptake was drawn. The other 61 breast carcinoma patients underwent routine lymphatic mapping. Sentinel lymph node biopsy (SLNB) and axillary lymph node dissection (ALND) were both performed in all 71 patients. Fresh SLNs and all axillary nodes were sent for pathological examination using hematoxylin and eosin (H&E) staining. RESULTS: (99m)Tc-Rituximab, with a yield of about 95.0%, can show SLN status in both mice and patients. The fusion image showed SLNs clearly, even the depth of SLNs in the axilla. The results of dynamic SLN mapping showed visible SLN starting from 10 min, up to 16 h after injecting tracer, however, secondary lymph nodes were not detectable at all. In mice, the ratio of SLN/background was 2.1, the rate of uptake was about 3.0% to 3.5%, and the equation of the curve was produced as: y = 0.036x + 2.7875, r(2) = 0.9787. For breast cancer patients, the uptake rate was different from case to case, but the cure seemed to be consistent with logarithm. The result of SLNB and ALND showed that the sensitivity and accuracy of SLNB was both 100.0%. The average number of SLNs found in each case was 2.6. Of nineteen breast cancer patients (26.8%) with lymph node metastasis, 11 were found to only have SLN metastasis. CONCLUSION: (99m)Tc-Rituximab, as a new tracer to mapping sentinel lymph node for breast cancer patient, is able to show the status of sentinel lymph node reliably. The fusing image is easy to obtain and be interpreted by the clinician.

[Preliminary study of new imaging agent, 99mTc-Rituximab, for sentinel lymph node biopsy of primary breast cancer].

OBJECTIVE: To study the feasibility and effects of new imaging agent, 99mTc-Rituximab, for sentinel lymph nodes biopsy (SLNB) of primary breast cancer. METHODS: SLNB were performed in eighty-five primary breast cancer patients using 99mTc-Rituximab combined with patent blue. Metastases in sentinel lymph nodes were detected with routine pathologic and immunohistochemistry method. RESULTS: The successful rate of SLNB using combining method of 99mTc-Rituximab and patent blue was 96% (82/85). Thirty cases of SLN (37%, 30/82) were metastasis positive, including twenty-four positive cases by HE staining and six by immunohistochemistry method. SLN was the only metastasis lymph nodes in 18/30 cases. One case has false negative SLN metastasis. The sensitivity and accuracy of SLNB were 97% (30/31) and 99% (81/82). The specificity was 100% (51/51). The false negative rate was 3% (1/30) and the negative predictive value was 98% (51/52). The positive predictive value was 100% (31/31). Internal mammary sentinel lymph node lymphoscintigraphy was positive in eleven cases but all of them were confirmed metastases negative by pathologic examination. CONCLUSIONS: 99mTc-Rituximab, as a new imaging agent, can keep SLN imaging durable and can make SLNB more convenient. Through primary clinical manifestation, higher sensitivity and accuracy could obtained by combining method of 99mTc-Rituximab and patent blue for SLNB of primary breast cancer.