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Nucl Med Biol. 2011 Apr;38(3):331-7. doi: 10.1016/j.nucmedbio.2010.10.005. Epub 2010 Dec 3.

Development of positron emission tomography probe of 64Cu-labeled anti-C-kit 12A8 Fab to measure protooncogene C-kit expression.

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Diagnostic Imaging Group, Molecular Imaging Center, National Institute of Radiological Sciences, Inage-ku, Chiba 263-8555, Japan.



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 (64)Cu-labeled Fab of anti-c-kit antibody 12A8 as a positron emission tomography (PET) imaging probe.


(111)In- or (125)I-Labeled 12A8 Fab was 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 (64)Cu and evaluated by PET.


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 [(111)In]Fab was lower than that of [(111)In]IgG, the faster blood clearance of [(111)In]Fab provided higher tumor-to-blood ratio at 6 h postinjection onwards. Blood clearance of (64)Cu-labeled 12A8 Fab was slower than that of [(111)In]Fab, but PET using [(64)Cu]Fab clearly visualized the tumor at 6 h postinjection onwards.


The (64)Cu-labeled 12A8 Fab could be used for c-kit-specific PET imaging and might help in selecting appropriate patients for c-kit-targeted treatments.

[Indexed for MEDLINE]

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