title: Comparison of biological properties of99mTc-labeled cyclic RGD Peptide trimer and dimer useful as SPECT radiotracers for tumor imaging.
abstract: BACKGROUND
  This study sought to evaluate a99mTc-labeled trimeric cyclic RGD peptide (99mTc-4P-RGD3) as the new radiotracer for tumor imaging. The objective was to compare its biological properties with those of99mTc-3P-RGD2in the same animal model.
  
  
  METHODS
  HYNIC-4P-RGD3was prepared by reacting 4P-RGD3with excess HYNIC-OSu in the presence of diisopropylethylamine.99mTc-4P-RGD3was prepared using a kit formulation, and evaluated for its tumor-targeting capability and biodistribution properties in the BALB/c nude mice with U87MG human glioma xenografts. Planar and SPECT imaging studies were performed in athymic nude mice with U87MG glioma xenografts. For comparison purpose,99mTc-3P-RGD2(a αvβ3-targeted radiotracer currently under clinical evaluation for tumor imaging in cancer patients) was also evaluated in the same animal models. Blocking experiments were used to demonstrate the αvβ3specificity of99mTc-4P-RGD3.
  
  
  RESULTS
  99mTc-4P-RGD3was prepared with >95% RCP and high specific activity (~200GBq/μmol).99mTc-4P-RGD3and99mTc-3P-RGD2shared almost identical tumor uptake and similar biodistribution properties.99mTc-4P-RGD3had higher uptake than99mTc-3P-RGD2in the intestines and kidneys; but it showed better metabolic stability. The U87MG tumors were clearly visualized by SPECT with excellent contrast with99mTc-4P-RGD3and99mTc-3P-RGD2.
  
  
  CONCLUSIONS
  Increasing peptide multiplicity from 3P-RGD2to 4P-RGD3offers no advantages with respect to the tumor-targeting capability.99mTc-4P-RGD3is as good a SPECT radiotracer as99mTc-3P-RGD2for imaging αvβ3-positive tumors.
authors.affiliation: Department of Nuclear Medicine, Fuwai Hospital, the National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Zuo-Quan
authors.initials: ZQ
authors.lastname: Zhao
authors.affiliation: Department of Nuclear Medicine, Fuwai Hospital, the National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China; School of Health Sciences, Purdue University, West Lafayette, USA.
authors.forename: Yong
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Nuclear Medicine, Fuwai Hospital, the National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. Electronic address: nuclearfw@126.com.
authors.forename: Wei
authors.initials: W
authors.lastname: Fang
authors.affiliation: School of Health Sciences, Purdue University, West Lafayette, USA. Electronic address: liu100@purdue.edu.
authors.forename: Shuang
authors.initials: S
authors.lastname: Liu
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D019281:Dimerization; D004355:Drug Stability; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D006834:Hydrazines / Q000737:chemistry; D039302:Integrin alphaVbeta3 / Q000378:metabolism; D007553:Isotope Labeling; D051379:Mice; D009539:Nicotinic Acids / Q000737:chemistry; D010456:Peptides, Cyclic / Q000737:chemistry* / Q000493:pharmacokinetics; D058105:Polymerization; D011849:Radioactive Tracers; D011854:Radiochemistry; D000072098:Single Photon Emission Computed Tomography Computed Tomography / Q000379:methods*; D013667:Technetium / Q000737:chemistry*; D014018:Tissue Distribution
chemical_list: C120392:6-hydrazinopyridine-3-carboxylic acid; D006834:Hydrazines; D039302:Integrin alphaVbeta3; D009539:Nicotinic Acids; D010456:Peptides, Cyclic; D011849:Radioactive Tracers; C507169:cyclic arginine-glycine-aspartic acid peptide; D013667:Technetium
keywords: (99m)Tc-trimeric cyclic RGD peptide; SPECT; integrin α(v)β(3); tumor imaging