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KMID : 1145520190050010054
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Journal of Radiopharmaceuticals and Molecular Probes
2019 Volume.5 No. 1 p.54 ~ p.60
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Synthesis and evaluation of 64Cu-labeled avidin for lymph node imaging
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Kang Choong-Mo
Kim Hyun-Jung
Lee Yong-Jin
Choe Yearn-Seong
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Abstract
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Sentinel lymph node (SLN) imaging plays an important role in surgery of patients with breast cancer and melanoma. In this study, avidin (Av), a tetrameric protein glycosylated with mannose and N-acetylglucosamine molecules, was labeled with 64Cu and then evaluated for LN imaging. 64Cu-Labeled NeutrAvidinTM (NAv), a nonglycosylated form of Av, was used for comparison. 1,4,7,10-Tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid (DOTA)-conjugated Av and NAv were prepared from the corresponding proteins and DOTA-NHS ester, which were then labeled with copper-64 and purified using PD-10 columns. The numbers of DOTA molecules conjugated to Av and NAv were 4.9 and 3.3, respectively. [64Cu]Cu-DOTA-conjugated Av and NAv were prepared in 93% and 73% radiochemical yields, respectively. In vitro serum stability study showed that copper-64 remained stable on all radiotracers for 24 h (>97%). MicroPET/CT images showed that high radioactivity was accumulated in LNs within 15 min after footpad-injection of radiotracers. Tissue distribution data of mice demonstrated significantly higher uptake in the popliteal (PO) LN than lumbar (LU) LN for 64Culabeled Av (relative % ID/g excluding the injection sites: 66.2% and 26.0%, respectively) compared with those of 64Cu-labeled NAv (43.0% and 49.2%, respectively). The results of this study suggest that mannose molecules on Av enabled the radiotracer to retain in the first LN after mouse footpad-injection.
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KEYWORD
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Sentinel lymph node, Avidin, NeutrAvidin, Copper-64, Mannose, PET/CT
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