Quantitative immuno-positron emission tomography imaging of HER2-positlve tumor xenografts with an iodine-124 labeled anti-HER2 diabody

Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA.
Cancer Research (Impact Factor: 9.28). 03/2005; 65(4):1471-8. DOI: 10.1158/0008-5472.CAN-04-2008
Source: PubMed

ABSTRACT Positron emission tomography (PET) provides an effective means of both diagnosing/staging several types of cancer and evaluating efficacy of treatment. To date, the only U.S. Food and Drug Administration-approved radiotracer for oncologic PET is (18)F-fluoro-deoxyglucose, which measures glucose accumulation as a surrogate for malignant activity. Engineered antibody fragments have been developed with the appropriate targeting specificity and systemic elimination properties predicted to allow for effective imaging of cancer based on expression of tumor associated antigens. We evaluated a small engineered antibody fragment specific for the HER2 receptor tyrosine kinase (C6.5 diabody) for its ability to function as a PET radiotracer when labeled with iodine-124. Our studies revealed HER2-dependent imaging of mouse tumor xenografts with a time-dependent increase in tumor-to-background signal over the course of the experiments. Radioiodination via an indirect method attenuated uptake of radioiodine in tissues that express the Na/I symporter without affecting the ability to image the tumor xenografts. In addition, we validated a method for using a clinical PET/computed tomography scanner to quantify tumor uptake in small-animal model systems; quantitation of the tumor targeting by PET correlated with traditional necropsy-based analysis at all time points analyzed. Thus, diabodies may represent an effective molecular structure for development of novel PET radiotracers.

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Available from: Calvin Shaller, Jan 27, 2014
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    • "However, decreased immunogenicity and univalent antigen binding of scFvs have limited its application [17] [18] [19]. To overcome these limitations, both covalent dimeric scFv (di-scFv) and noncovalent diabody constructs have been studied; as bivalent molecules, they exhibit greater avidity than the smaller univalent scFv fragments [20] [21] [22] [23]. "
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    • "Bispecific - scFvs were expressed in Escherichia coli and purified by sequential IMAC and size - exclusion chromatography essentially as described ( Robinson et al , 2005 ) . Binding of the A5 and the ALM bs - scFv to ErbB2 and ErbB3 ECDs was characterized by SPR using ErbB2 and ErbB3 ECDs ( Horak et al , 2005 ) as target antigens and "
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