title: Evaluation of 99mTc-peptide-ZHER2:342 Affibody® molecule for in vivo molecular imaging.
abstract: OBJECTIVE
  The aim of this study was to develop an improved method for labelling ZHER2:342 with Technetium-99m ((99m)Tc) using Gly-(d) Ala-Gly-Gly as a chelator and to evaluate the feasibility of its use for visualization of HER2 expression in vivo.
  
  
  METHODS
  The Affibody® molecule ZHER2:342 was synthesized by Fmoc/tBu solid phase synthesis. The chelator, Gly-(d) Ala-Gly-Gly, was introduced by manual synthesis as the N-terminal extensions of ZHER2:342. ZHER2:342 was labelled with (99m)Tc. The labelling efficiency, radiochemical purity and in vitro stability of the labelled molecular probe were analysed by reversed-phase high performance liquid chromatography. Biodistribution and molecular imaging using (99m)Tc-peptide-ZHER2:342 were performed.
  
  
  RESULTS
  The molecular probe was successfully synthesized and labelled with (99m)Tc with the labelling efficiency of 98.10 ± 1.73% (n=5). The radiolabelled molecular probe remained highly stable in vitro. The molecular imaging showed high uptake in HER2-expressing SKOV-3 xenografts, whereas the MDA-MB-231 xenografts with low HER2 expression were not clearly imaged at any time after the injection of (99m)Tc-peptide-ZHER2:342. The predominant clearance pathway for (99m)Tc-peptide-ZHER2:342 was through the kidneys. Conculsion: (99m)Tc-peptide-ZHER2:342 using Gly-(d) Ala-Gly-Gly as a chelator is a promising tracer agent with favourable biodistribution and imaging properties that may be developed as a radiopharmaceutical for the detection of HER2-positive malignant tumours.
  
  
  CONCLUSIONS
  The (99m)Tc-peptide-ZHER2:342 molecular probe is a promising tracer agent, and the results in this study provide a foundation for future development of protocols for earlier visual detection of cancer in the clinical setting.
authors.affiliation: Department of Nuclear Medicine, The Fourth Affiliated Hospital of Hebei Medical University, Shijiazhuang, China.
authors.forename: J-M
authors.initials: JM
authors.lastname: Zhang
authors.forename: X-M
authors.initials: XM
authors.lastname: Zhao
authors.forename: S-J
authors.initials: SJ
authors.lastname: Wang
authors.forename: X-C
authors.initials: XC
authors.lastname: Ren
authors.forename: N
authors.initials: N
authors.lastname: Wang
authors.forename: J-Y
authors.initials: JY
authors.lastname: Han
authors.forename: L-Z
authors.initials: LZ
authors.lastname: Jia
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D008819:Mice, Nude; D057054:Molecular Imaging / Q000379:methods*; D009842:Oligopeptides; D010051:Ovarian Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism*; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000737:chemistry; D011897:Random Allocation; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics; D013667:Technetium / Q000737:chemistry / Q000493:pharmacokinetics; D014018:Tissue Distribution; D014407:Tumor Cells, Cultured
chemical_list: D009842:Oligopeptides; D019275:Radiopharmaceuticals; D018719:Erb-b2 Receptor Tyrosine Kinases; D011993:Recombinant Fusion Proteins; D013667:Technetium; C533351:affibody (ZHER2-342)2; C516501:alanyl-glycyl-glycine