量研学術機関リポジトリ「QST-Repository」は、国立研究開発法人 量子科学技術研究開発機構に所属する職員等が生み出した学術成果（学会誌発表論文、学会発表、研究開発報告書、特許等）を集積しインターネット上で広く公開するサービスです。 Welcome to QST-Repository where we accumulates and discloses the academic research results(Journal Publications, Conference presentation, Research and Development Report, Patent, etc.) of the members of National Institutes for Quantum Science and Technology.
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Introduction: C-kit is an important diagnostic and therapeutic target molecule for several malignancies, and c-kit-targeted drugs have been used clinically. Because abundant c-kit expression in tumors is a prerequisite for successful c-kit-targeted therapy, imaging of c-kit expression is expected to play a pivotal role in the therapeutic decision for each patient. We evaluated 64Cu-labeled Fab of anti-c-kit antibody 12A8 as a positron emission tomography (PET) imaging probe. Methods: 111In- or 125I-labeled 12A8 Fab were evaluated in vitro by cell binding, competitive inhibition, and cellular internalization assays and in vivo by biodistribution in mice bearing c-kit-expressing and -non-expressing tumors. Next, Fab fragment was labeled with the positron emitter 64Cu and evaluated by PET. Results: Radiolabeled 12A8 Fab showed specific binding to c-kit-expressing cells with high affinity, and internalized into cells after binding to c-kit on cell surface. Although tumor accumulation of [111In]Fab was lower than that of [111In]IgG, the faster blood clearance of [111In]Fab provided higher tumor-to-blood ratio at 6 h postinjection onwards. Blood clearance of 64Cu-labeled 12A8 Fab was slower than that of [111In]Fab, but PET using [64Cu]Fab clearly visualized the tumor at 6 h postinjection onwards. Conclusion: The 64Cu-labeled 12A8 Fab could be used for c-kit-specific PET imaging and might help in selecting appropriate patients for c-kit-targeted treatments.
Development of Positron Emission Tomography Probe of 64Cu-labeled Anti-c-kit 12A8 Fab to Measure Protooncogene C-kit Expression
