期刊
CLINICAL CANCER RESEARCH
卷 19, 期 24, 页码 6820-6829出版社
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/1078-0432.CCR-13-0626
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资金
- National Cancer Institute grant support [ICMIC P50CA114747]
Purpose: The aim of this article was to evaluate the use of a novel engineered anti-CD20 protein based on the 10 kDa human fibronectin type 3 domain (FN3) and subsequently compare with Cu-64-rituximab for positron emission tomography (PET) imaging of CD20. Experimental Design: The engineered FN3(CD20) and FN3(WT) were produced in Escherichia coli cells at 2 to 5 mg/L, conjugated to DOTA, labeled with 64 Cu, and used for PET imaging of huCD20 expression in B cells. Humanized transgenic mice and subcutaneously xenografted mice each received intravenous Cu-64-FN3(CD20) or FN3(WT) (3.7 MBq/4 mg Do-FN3 in 200 mL PBS). Control group received a blocking dose (50-fold excess) of unconjugated FN3(CD20) two hours before radiotracer injection. PET imaging was carried out at 1 to 24 hours postinjections. Results: In vitro assay demonstrated FN3 binds CD20 with 20 nmol/L affinity on CD20-expressing cells. Cu-64-FN3(CD20) showed clear, high-contrast visualization of huCD20-expressing B cells in the spleen of transgenic mice as early as 1 hour postinjection [38 +/- 3% injected dose (ID)/g] and exhibited a spleen-toblood ratio of 13 by 4 hours. This is higher uptake (P = 0.04) and 10-fold greater signal-to-background (P = 0.04) than the Cu-64-rituximab antibody radiotracer. Tumor uptake (16.8 +/- 1.6 vs. 5.6 +/- 1.4% ID/g) and tumor: background ratios were superior for FN3(CD20) relative to rituximab in xenograft studies as well. Conclusions: The Cu-64-Do-FN3(CD20) radiotracer represents a novel small, high-affinity binder for imaging human CD20, which may be well suited for B-cell non-Hodgkin's lymphoma imaging in patients at early time points. (C) 2013 AACR.
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