title: ⁶⁸Ga-NODAGA-VEGF₁₂₁ for in vivo imaging of VEGF receptor expression.
abstract: OBJECTIVE
  Vascular endothelial growth factor (VEGF) is a crucial regulator of angiogenesis. In this study, we labeled VEGF₁₂₁ with (68)Ga using a hydrophilic chelating agent, NODAGA and evaluated the resulting (68)Ga-NODAGA-VEGF₁₂₁ for in vivo imaging of VEGF receptor (VEGFR) expression.
  
  
  METHODS
  NODAGA-VEGF₁₂₁ was prepared and its binding affinity for VEGFR2 was measured using (125)I-VEGF₁₂₁. (68)Ga-NODAGA-VEGF₁₂₁ was prepared by labeling NODAGA-VEGF₁₂₁ with (68)GaCl3 followed by purification using a PD-10 column. Human aortic endothelial cell (HAEC) binding studies of (68)Ga-NODAGA-VEGF₁₂₁ were performed at 37°C for 4 h. MicroPET imaging followed by biodistribution studies were performed in U87MG tumor-bearing mice injected with (68)Ga-NODAGA-VEGF₁₂₁. Immunofluorescence staining of the tumor tissues was performed to verify VEGFR2 expression.
  
  
  RESULTS
  Binding affinity of NODAGA-VEGF₁₂₁ for VEGFR2 was found to be comparable to that of VEGF₁₂₁. (68)Ga-NODAGA-VEGF₁₂₁ was prepared in 47.8% yield with specific activity of 3.4 GBq/mg. (68)Ga-NODAGA-VEGF₁₂₁ was avidly taken up by HAECs with a time-dependent increase from 9.88 %ID at 1 h to 20.86 %ID at 4h. MicroPET imaging of mice demonstrated high liver and spleen uptake with clear visualization of tumor at 1h after injection. ROI analysis of tumors revealed 2.53 ± 0.11 %ID/g at 4 h after injection. In the blocking study, tumor uptake was inhibited by 29% at 4 h. Subsequent biodistribution studies demonstrated tumor uptake of 2.38 ± 0.15 %ID/g. Immunofluorescence staining of the tumor tissues displayed high level of VEGFR2 expression.
  
  
  CONCLUSIONS
  These results demonstrate that (68)Ga-NODAGA-VEGF₁₂₁ led to VEGFR-specific distribution in U87MG tumor-bearing mice. This study also suggests that altered physicochemical properties of VEGF₁₂₁ after radiolabeling may affect biodistribution of the radiolabeled VEGF₁₂₁.
authors.affiliation: Department of Nuclear Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Ilwon-dong, Kangnam-ku, Seoul 135-710, Korea; Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul 135-710, Korea.
authors.forename: Choong Mo
authors.initials: CM
authors.lastname: Kang
authors.forename: Hyun-Jung
authors.initials: HJ
authors.lastname: Koo
authors.forename: Yearn Seong
authors.initials: YS
authors.lastname: Choe
authors.forename: Joon Young
authors.initials: JY
authors.lastname: Choi
authors.forename: Kyung-Han
authors.initials: KH
authors.lastname: Lee
authors.forename: Byung-Tae
authors.initials: BT
authors.lastname: Kim
mesh_terms: D000085:Acetates / Q000737:chemistry*; D000818:Animals; D045744:Cell Line, Tumor; D002614:Chelating Agents / Q000737:chemistry*; D004355:Drug Stability; D005710:Gallium Radioisotopes; D005786:Gene Expression Regulation; D006573:Heterocyclic Compounds, 1-Ring / Q000737:chemistry*; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D051379:Mice; D049268:Positron-Emission Tomography / Q000379:methods*; D040262:Receptors, Vascular Endothelial Growth Factor / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000097:blood / Q000737:chemistry* / Q000493:pharmacokinetics
chemical_list: C572723:1-(1,3-carboxypropyl)-4,7-carboxymethyl-1,4,7-triazacyclononane; D000085:Acetates; D002614:Chelating Agents; D005710:Gallium Radioisotopes; D006573:Heterocyclic Compounds, 1-Ring; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D040262:Receptors, Vascular Endothelial Growth Factor
keywords: (68)Ga-NODAGA-VEGF(121); Angiogenesis; MicroPET; VEGFR