(99m)Tc-labeled monomeric and dimeric NGR peptides for SPECT imaging of CD13 receptor in tumor-bearing mice.

Abstract

CD13 receptor plays a critical role in tumor angiogenesis and metastasis. We therefore aimed to develop (99m)Tc-labeled monomeric and dimeric NGR-containing peptides, namely, NGR1 and NGR2, for SPECT imaging of CD13 expression in HepG2 hepatoma xenografts. Both NGR-containing monomer and dimer were synthesized and labeled with (99m)Tc. In vivo receptor specificity was demonstrated by successful blocking of tumor uptake of (99m)Tc-NGR dimer in the presence of 20 mg/kg NGR2 peptide. Western blot and immunofluorescence staining confirmed the CD13 expression in HepG2 cells. The NGR dimer showed higher binding affinity and cell uptake in vitro than the NGR-containing monomer, presumably due to a multivalency effect. (99m)Tc-Labeled monomeric and dimeric NGR-containing peptides were subjected to SPECT imaging and biodistribution studies. SPECT scans were performed in HepG2 tumor-bearing mice at 1, 4, 12, and 24 h post-injection of ~7.4 MBq tracers. The metabolism of tracers was determined in major organs at different time points after injection which demonstrated rapid, significant tumor uptake and slow tumor washout for both traces. Predominant clearance from renal and hepatic system was also observed in (99m)Tc-NGR1 and (99m)Tc-NGR2. In conclusion, monomeric and dimeric NGR peptide were developed and labeled with (99m)Tc successfully, while the high integrin avidity and long retention in tumor make (99m)Tc-NGR dimer a promising agent for tumor angiogenesis imaging.

• Authors: Wenhui Ma, Fei Kang, Zhe Wang, Weidong Yang, Guiyu Li, Xiaowei Ma, Guoquan Li, Kai Chen, Yingqi Zhang, Jing Wang
• Journal: Amino acids (Amino Acids) Vol. 44 Issue 5 Pg. 1337-45 (May 2013) ISSN: 1438-2199 [Electronic] Austria
• PMID: 23456486 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Oligopeptides
• Organotechnetium Compounds
• Peptides
• Radiopharmaceuticals
• technetium 99m bis(glycyl-aspargyl-glycyl-arginyl-glycine)lysyl-glycyl-lysine
• technetium 99m glycyl-asparagyl-glycyl-arginyl-glycine
• CD13 Antigens

Topics

• Animals
• CD13 Antigens (metabolism)
• Carcinoma, Hepatocellular (diagnostic imaging, metabolism)
• Drug Stability
• HT29 Cells
• Hep G2 Cells
• Humans
• Liver Neoplasms, Experimental (diagnostic imaging, metabolism)
• Mice
• Neoplasm Transplantation
• Oligopeptides (metabolism, pharmacokinetics)
• Organotechnetium Compounds (metabolism, pharmacokinetics)
• Peptides (metabolism, pharmacokinetics)
• Radiopharmaceuticals (metabolism, pharmacokinetics)
• Tissue Distribution
• Tomography, Emission-Computed, Single-Photon