Catarina Xavier1, Anneleen Blykers2, Ilse Vaneycken3, Matthias D'Huyvetter2, Jan Heemskerk4, Tony Lahoutte3, Nick Devoogdt5, Vicky Caveliers3. 1. In vivo Cellular and Molecular Imaging Laboratory (ICMI), Vrije Universiteit Brussel, Brussels, Belgium. Electronic address: cxavier@vub.ac.be. 2. In vivo Cellular and Molecular Imaging Laboratory (ICMI), Vrije Universiteit Brussel, Brussels, Belgium. 3. In vivo Cellular and Molecular Imaging Laboratory (ICMI), Vrije Universiteit Brussel, Brussels, Belgium; Nucleaire Geneeskunde, UZ Brussel, Brussels, Belgium. 4. Nucleaire Geneeskunde, UZ Brussel, Brussels, Belgium. 5. In vivo Cellular and Molecular Imaging Laboratory (ICMI), Vrije Universiteit Brussel, Brussels, Belgium; Laboratory of Cellular and Molecular Immunology, Vrije Universiteit Brussel, Brussels, Belgium.
Abstract
INTRODUCTION: Radiolabeled nanobodies are exciting new probes for molecular imaging due to high affinity, high specificity and fast washout from the blood. Here we present the labeling of an anti-HER2 nanobody with (18)F and its validation for in vivo assessment of HER2 overexpression. METHODS: The GMP grade anti-HER2 nanobody was labeled with the prosthetic group, N-succinimidyl-4-[(18)F]fluorobenzoate ([(18)F]-SFB), and its biodistribution, tumor targeting and specificity were evaluated in mouse and rat tumor models. RESULTS: [(18)F]FB-anti-HER2 nanobody was prepared with a 5-15% global yield (decay corrected) and a specific activity of 24.7 ± 8.2 MBq/nmol. In vivo studies demonstrated a high specific uptake for HER2 positive xenografts (5.94 ± 1.17 and 3.74 ± 0.52%IA/g, 1 and 3h p.i.) with high tumor-to-blood and tumor-to-muscle ratios generating high contrast PET imaging. The probe presented fast clearance through the kidneys (4%IA/g at 3h p.i.). [(18)F]FB-anti-HER2 nanobody is able to image HER2 expressing tumors when co-administered with the anti-HER2 therapeutic antibody trastuzumab (Herceptin), indicating the possibility of using the tracer in patients undergoing Herceptin therapy. CONCLUSIONS: The GMP grade anti-HER2 nanobody was labeled with (18)F. This new PET probe for imaging HER2 overexpression in tumors has ample potential for clinical translation.
INTRODUCTION: Radiolabeled nanobodies are exciting new probes for molecular imaging due to high affinity, high specificity and fast washout from the blood. Here we present the labeling of an anti-HER2 nanobody with (18)F and its validation for in vivo assessment of HER2 overexpression. METHODS: The GMP grade anti-HER2 nanobody was labeled with the prosthetic group, N-succinimidyl-4-[(18)F]fluorobenzoate ([(18)F]-SFB), and its biodistribution, tumor targeting and specificity were evaluated in mouse and rattumor models. RESULTS: [(18)F]FB-anti-HER2 nanobody was prepared with a 5-15% global yield (decay corrected) and a specific activity of 24.7 ± 8.2 MBq/nmol. In vivo studies demonstrated a high specific uptake for HER2 positive xenografts (5.94 ± 1.17 and 3.74 ± 0.52%IA/g, 1 and 3h p.i.) with high tumor-to-blood and tumor-to-muscle ratios generating high contrast PET imaging. The probe presented fast clearance through the kidneys (4%IA/g at 3h p.i.). [(18)F]FB-anti-HER2 nanobody is able to image HER2 expressing tumors when co-administered with the anti-HER2 therapeutic antibody trastuzumab (Herceptin), indicating the possibility of using the tracer in patients undergoing Herceptin therapy. CONCLUSIONS: The GMP grade anti-HER2 nanobody was labeled with (18)F. This new PET probe for imaging HER2 overexpression in tumors has ample potential for clinical translation.
Authors: Zhengyuan Zhou; Ganesan Vaidyanathan; Darryl McDougald; Choong Mo Kang; Irina Balyasnikova; Nick Devoogdt; Angeline N Ta; Brian R McNaughton; Michael R Zalutsky Journal: Mol Imaging Biol Date: 2017-12 Impact factor: 3.488
Authors: Matthias D'Huyvetter; Jens De Vos; Catarina Xavier; Marek Pruszynski; Yann G J Sterckx; Sam Massa; Geert Raes; Vicky Caveliers; Michael R Zalutsky; Tony Lahoutte; Nick Devoogdt Journal: Clin Cancer Res Date: 2017-07-27 Impact factor: 12.531
Authors: Zhengyuan Zhou; Satish K Chitneni; Nick Devoogdt; Michael R Zalutsky; Ganesan Vaidyanathan Journal: Bioorg Med Chem Date: 2018-03-15 Impact factor: 3.641