Choong Mo Kang1, Hyun-Jung Koo, Yearn Seong Choe, Joon Young Choi, Kyung-Han Lee, Byung-Tae Kim. 1. 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.
Abstract
PURPOSE: 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.
PURPOSE: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: Florian C Maier; Julia Schmitt; Andreas Maurer; Walter Ehrlichmann; Gerald Reischl; Konstantin Nikolaou; Rupert Handgretinger; Bernd J Pichler; Wolfgang M Thaiss Journal: Oncotarget Date: 2016-10-11
Authors: Eva Rainer; Hao Wang; Tatjana Traub-Weidinger; Georg Widhalm; Barbara Fueger; Jingling Chang; Zhaohui Zhu; Christine Marosi; Alexander Haug; Marcus Hacker; Shuren Li Journal: Eur J Nucl Med Mol Imaging Date: 2018-07-30 Impact factor: 9.236
Authors: Bogdan Mitran; Rezan Güler; Francis P Roche; Elin Lindström; Ram Kumar Selvaraju; Filippa Fleetwood; Sara S Rinne; Lena Claesson-Welsh; Vladimir Tolmachev; Stefan Ståhl; Anna Orlova; John Löfblom Journal: Theranostics Date: 2018-08-07 Impact factor: 11.556