Imaging targeted at tumor with ¹⁸⁸Re-labeled VEGF₁₈₉ exon 6-encoded peptide and effects of the transfecting truncated KDR gene in tumor-bearing nude mice☆

Abstract 

Introduction

Planar imaging of ¹⁸⁸Re-labeled vascular endothelial growth factor (VEGF)₁₈₉ exon 6-encoded peptide (QKRKRKKSRYKS) with single photon emission computed tomography (SPECT) in tumor-bearing nude mice and effects of the transfecting truncated KDR gene on its imaging were investigated, so as to provide a basis for further applying the peptide to tumor-targeted radionuclide treatment.

Methods

QKRKRKKSRYKS, coupling with mercaptoacetyltriglycine (MAG₃) chelator was labeled with ¹⁸⁸Re; then in vivo distribution, planar imaging with SPECT and blocking experiment in tumor-bearing nude mice were analyzed. Recombinant adenovirus vectors carrying the truncated KDR gene were constructed to transfect tumor tissues to evaluate the effects of truncated KDR on the in vivo distribution and tumor planar imaging of ¹⁸⁸Re-MAG₃–QKRKRKKSRYKS in tumor-bearing nude mice.

Results

The labeled peptide exhibited a sound receptor binding activity. Planar imaging with SPECT demonstrated significant radioactivity accumulation in tumor 1 h after injection of the labeled peptide and disappearance of radioactivity 3 h later. Significant radioactivity accumulation was also observed in the liver, intestines and kidneys but was not obvious in other tissues. An hour after injection of the labeled peptide, the percentage of the injected radioactive dose per gram (%ID/g) of tumor and tumor/contralateral muscle tissues ratio were 1.98±0.38 and 2.53±0.33, respectively, and increased to 3.08±0.84 and 3.61±0.59 in the group transfected with the truncated KDR gene, respectively, and radioactivity accumulation in tumor with planar imaging also increased significantly in the transfection group.

Conclusion

¹⁸⁸Re-MAG₃–QKRKRKKSRYKS can accumulate in tumor tissues, which could be increased by the transfection of truncated KDR gene. This study provides a basis for further applying the peptide to tumor targeted radionuclide imaging and treatment.

Keywords: ¹⁸⁸Re, Radiolabeled proteins, Peptides, Radionuclide therapy, Receptor imaging, Tumor imaging