A Ga-68 labeled peptide for imaging of αvβ6 positive tumor

Objectives The α_vβ₆ integrin has been reported as a promising target to develop imaging agents for cancers. A 7-mer peptide sequence derived from phage display that specifically targets the α_vβ₆ integrin was identified. To evaluate its potential for α_vβ₆ targetedimaging, the PEGylated peptide was conjugated with a NOTA-based bifunctional chelator and labeled with ⁶⁸Ga.

Methods The 7-mer-PEG conjugate was synthesized by Fmoc solid-phase chemistry, followed by the coupling of a NOTA derivative to the N-terminus. The NOTA-7-mer-PEG conjugate was labeled with ⁶⁸Ga under a mild condition. The PET scans were performed in nude or SCID mice bearing U87MG, H460, H2009, or T47D xenografts. Western blot and flow cytometry were performed to verify the correlation of the α_vβ₆ expression in these cell lines with the imaging findings.

Results The peptide conjugate was prepared and characterized by HPLC and MALDI-Mass spectroscopy. The specific activity of the ⁶⁸Ga labeled peptide conjugate was up to 7.4 ´ 10⁵ Ci/mol with radiochemical purity > 99%. Rapid uptake (< 30 min) and selective retention (> 1.5 h) in H2009 and T47D tumors were observed on the PET images. The ratio of tumor-to-muscle was 5.3 for H2009 tumor at 1.5 h p.i. and 3.8 for T47D tumor at 2 h p.i. based on PET imaging quantification. The α_vβ₆ expression determined by the western blot and flow cytometry assays was well correlated with the imaging data varying with the tested cell lines.

Conclusions We have shown the potential of this 7-mer peptide conjugate for PET imaging of α_vβ₆ positive tumors. Further studies to quantify the in vivo α_vβ₆ expression are in progress.

Research Support 2006 SNM Bradley-Alavi FellowshipNIH 1RO1CA106646The Welch Foundation (I1622)