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CRC Laboratories, Department of Clinical Oncology, Royal Free Hospital School of Medicine, London, United Kingdom
University Hospital Utrecht, The Netherlands
Department of Clinical Oncology and MRC Center, Cambridge, United Kingdom
Correspondence: For correspondence or reprints contact: Kerry Chester, PhD, CRC Laboratories, Department of Clinical Oncology, Royal Free Hospital School of Medicine, Rowland Hill St., London, NW3 2PF United Kingdom.
ABSTRACT
Single-chain Fv (scFv) antibody fragments have potential for clinical imaging studies because of their rapid tumor penetration and high tumor-to-tissue ratios at early time points. ScFvs clear rapidly from the circulation so radiolabels such as 99mTc which have short half-lives are desirable, but the free thiol groups necessary for labeling with 99mTc are not normally found on these molecules. Methods: We constructed a vector which enabled a free cysteine to be linked to the C-terminus of scFvs. MFE-23, a scFv directed against carcinoembryonic antigen (CEA), was cloned into this vector and cys-tagged MFE-23 was labeled with 99mTc using a D-glucarate transfer method. Results: The radiolabeled product was stable in vivo and in vitro and showed favorable tumor-to-blood ratios in vivo at early time points (4:1 at 24 hr and 8:1 at 48 hr), although high kidney levels were also detected. Conclusion: Our study demonstrates an effective method to enable scFvs radiolabeling with 99mTc and also shows the potential of using a 99mTc-labeled scFv for clinical imaging studies.
Key Words: single-chain Fv antibody fragments • technetium-99m
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