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  • Title: EGF receptor targeted tumor imaging with biotin-PEG-EGF linked to (99m)Tc-HYNIC labeled avidin and streptavidin.
    Author: Jung KH, Park JW, Paik JY, Quach CH, Choe YS, Lee KH.
    Journal: Nucl Med Biol; 2012 Nov; 39(8):1122-7. PubMed ID: 22819251.
    Abstract:
    INTRODUCTION: As direct radiolabeled peptides suffer limitations for in vivo imaging, we investigated the usefulness of radioloabeled avidin and streptavidin as cores to link peptide ligands for targeted tumor imaging. METHODS: Human epidermal growth factor (EGF) was site specifically conjugated with a single PEG-biotin molecule and linked to (99m)Tc-HYNIC labeled avidin-FITC (Av) or streptavidin-Cy5.5 (Sav). Receptor targeting was verified in vitro, and in vivo pharmacokinetic and biodistribution profiles were studied in normal mice. Scintigraphic imaging was performed in MDA-MB-468 breast tumor xenografted nude mice. RESULTS: Whereas both (99m)Tc-Av-EGF and (99m)Tc-Sav-EGF retained receptor-specific binding in vitro, the two probes substantially diverged in pharmacokinetic and biodistribution behavior in vivo. (99m)Tc-Av-EGF was rapidly eliminated from the circulation with a T1/2 of 4.3 min, and showed intense hepatic accumulation but poor tumor uptake (0.6%ID/gm at 4 h). (99m)Tc-Sav-EGF displayed favorable in vivo profiles of longer circulation (T1/2β, 51.5 min) and lower nonspecific uptake that resulted in higher tumor uptake (3.8 %ID/gm) and clear tumor visualization at 15 h. CONCLUSION: (99m)Tc-HYNIC labeled streptavidin linked with growth factor peptides may be useful as a protein-ligand complex for targeted imaging of tumor receptors.
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