Imaging targeted at tumor with
6-encoded peptide and effects of the transfecting truncated
KDR gene in tumor-bearing nude mice
Zhe-xue Qin, Qian-wei Li, Guang-yuan Liu, Chao-xue Luo, Gan-feng Xie,
Lei Zheng, Ding-de Huang
Department of Nuclear Medicine, Southwest Hospital, Third Military Medical University, Chongqing 400038, China
Received 12 August 2008; received in revised form 17 January 2009; accepted 6 February 2009
Introduction: Planar imaging of
Re-labeled vascular endothelial growth factor (VEGF)
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 (MAG
) chelator was labeled with
Re; 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
–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.
–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.
© 2009 Elsevier Inc. All rights reserved.
Re; Radiolabeled proteins; Peptides; Radionuclide therapy; Receptor imaging; Tumor imaging
Vascular endothelial growth factor (VEGF), a major
angiogenesis-promoting factor, plays a pivotal role in tumor
angiogenesis, which exerts its biological actions through
VEGF receptors (VEGFRs) on the surface of target cells
[1–4]. Among the alternative splicing isoforms, VEGF
is thought to be the most potent for angiogenesis in
various tumors , and for VEGF
, the short-peptide
QKRKRKKSRYKS encoded by exon 6 comparatively has a
higher binding affinity than any other exon of it, without
activating the tyrosine kinase activity of VEGFRs; thus, the
peptide can antagonize the proangiogenesis action of VEGF
in a competitive manner [6–7].
VEGF receptors include VEGFR-1 (Flt-1), VEGFR-2
[kinase insert domain-containing receptor (KDR)/flk-1],
VEGFR-3 (Flt-4), Neuropilin-1 and Neuropilin-2 .Of
them, KDR plays a key role in tumor angiogenesis. KDR
comprises an extracellular ligand binding domain, a trans-
membrane domain and an intracellular tyrosine kinase
domain. The KDR expression is up-regulated under patholo-
gical conditions such as tumor cells, vascular endothelial cells
in tumors and prenatal development, while it is extremely
Available online at www.sciencedirect.com
Nuclear Medicine and Biology 36 (2009) 535 – 543
This study was supported by the National Natural Science
Foundation of China(30400114) and the Science Research Fund of Third
Military Medicine University 2004.
Corresponding author. Tel.: +86 023 68765432; fax: +86 023
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0969-8051/$ – see front matter © 2009 Elsevier Inc. All rights reserved.