Luis Michel Alonso Martinez1, François Harel2, Quang T Nguyen3, Myriam Létourneau4, Caroline D'Oliviera-Sousa3, Bernard Meloche3, Vincent Finnerty3, Alain Fournier5, Jocelyn Dupuis6, Jean N DaSilva7. 1. University of Montreal Hospital Research Centre, 900 rue Saint-Denis, Montréal, Québec H2X 3H8, Canada; Department of Biomedical Engineering, Faculty of Medicine, Université de Montréal, Pavillon Paul-G. Desmarais, 2960 chemin de la Tour, Montréal, Québec H3T 1J4, Canada; Research Center of the Montreal Heart Institute, 5000 Rue Bélanger, Montréal, Québec H1T 1C8, Canada. 2. Department of Biomedical Engineering, Faculty of Medicine, Université de Montréal, Pavillon Paul-G. Desmarais, 2960 chemin de la Tour, Montréal, Québec H3T 1J4, Canada; Research Center of the Montreal Heart Institute, 5000 Rue Bélanger, Montréal, Québec H1T 1C8, Canada; Department of Radiology, Radio-oncology and Nuclear Medicine, Université de Montréal, Pavillon Roger-Gaudry, 2900 Boulevard Edouard Montpetit, Montréal, Québec H3T 1J4, Canada. 3. Research Center of the Montreal Heart Institute, 5000 Rue Bélanger, Montréal, Québec H1T 1C8, Canada. 4. Laboratoire D'études Moléculaires et Pharmacologiques des Peptides, INRS-Institut Armand-Frappier, 531 boulevard des Prairies, Laval, Québec H7V 1B7, Canada. 5. Department of Radiology, Radio-oncology and Nuclear Medicine, Université de Montréal, Pavillon Roger-Gaudry, 2900 Boulevard Edouard Montpetit, Montréal, Québec H3T 1J4, Canada. 6. Research Center of the Montreal Heart Institute, 5000 Rue Bélanger, Montréal, Québec H1T 1C8, Canada; Department of Medicine, Université de Montréal, 2900 boulevard Edouard Montpetit, Montréal, Québec H3T 1J4, Canada. 7. University of Montreal Hospital Research Centre, 900 rue Saint-Denis, Montréal, Québec H2X 3H8, Canada; Department of Biomedical Engineering, Faculty of Medicine, Université de Montréal, Pavillon Paul-G. Desmarais, 2960 chemin de la Tour, Montréal, Québec H3T 1J4, Canada; Department of Radiology, Radio-oncology and Nuclear Medicine, Université de Montréal, Pavillon Roger-Gaudry, 2900 Boulevard Edouard Montpetit, Montréal, Québec H3T 1J4, Canada. Electronic address: jean.dasilva@umontreal.ca.
Abstract
INTRODUCTION: Adrenomedullin receptors are highly expressed in human alveolar capillaries and provide a molecular target for imaging the integrity of pulmonary microcirculation. In this work, we aimed to develop a NOTA-derivatized adrenomedullin analog (DFH17), radiolabeled with [18F]AlF, for PET imaging of pulmonary microcirculation. METHODS: Highly concentrated [18F](AlF)2+ (15 μL) was produced from purified fluorine-18 in NaCl 0.9%. Various complexation experiments were carried out at Al-to-NOTA molar ratios ranging from 1:1 to 1:40 to assess optimal radiolabeling conditions before using the peptide. DFH17 peptide (2 mM, pH 4) was radiolabeled with [18F](AlF)2+ for 15 min at 100 °C in a total volume of 60 μL. As part of the radiolabeling process, parameters such as fluorine-18 activity (~37 and 1480 MBq), concentration of AlCl3 (0.75, 2, 3, 6 or 10 mM) and the effects of hydrophilic organic solvent (aqueous vs ethanol 50%) were studied. The final formulation was tested for purity, identity and stability in saline. Initial in vivo evaluation of [18F]AlF-DFH17 was performed in normal rats by PET/CT. RESULTS: The scaled-up production of [18F]AlF-DFH17 was performed in high radiochemical and chemical purities in an overall radiochemical yield of 22-38% (at end-of-synthesis) within 60 min. The final formulation was stable in saline at different radioactive concentrations for 8 h. PET evaluation in rats revealed high lung-to-background ratios and no defluorination in vivo up to 1 h post-injection. CONCLUSION: The novel radioconjugate [18F]AlF-DFH17 appears to be a promising PET ligand for pulmonary microcirculation imaging.
INTRODUCTION:Adrenomedullin receptors are highly expressed in humanalveolar capillaries and provide a molecular target for imaging the integrity of pulmonary microcirculation. In this work, we aimed to develop a NOTA-derivatized adrenomedullin analog (DFH17), radiolabeled with [18F]AlF, for PET imaging of pulmonary microcirculation. METHODS: Highly concentrated [18F](AlF)2+ (15 μL) was produced from purified fluorine-18 in NaCl 0.9%. Various complexation experiments were carried out at Al-to-NOTA molar ratios ranging from 1:1 to 1:40 to assess optimal radiolabeling conditions before using the peptide. DFH17 peptide (2 mM, pH 4) was radiolabeled with [18F](AlF)2+ for 15 min at 100 °C in a total volume of 60 μL. As part of the radiolabeling process, parameters such as fluorine-18 activity (~37 and 1480 MBq), concentration of AlCl3 (0.75, 2, 3, 6 or 10 mM) and the effects of hydrophilic organic solvent (aqueous vs ethanol 50%) were studied. The final formulation was tested for purity, identity and stability in saline. Initial in vivo evaluation of [18F]AlF-DFH17 was performed in normal rats by PET/CT. RESULTS: The scaled-up production of [18F]AlF-DFH17 was performed in high radiochemical and chemical purities in an overall radiochemical yield of 22-38% (at end-of-synthesis) within 60 min. The final formulation was stable in saline at different radioactive concentrations for 8 h. PET evaluation in rats revealed high lung-to-background ratios and no defluorination in vivo up to 1 h post-injection. CONCLUSION: The novel radioconjugate [18F]AlF-DFH17 appears to be a promising PET ligand for pulmonary microcirculation imaging.
Authors: Luis Michel Alonso Martinez; François Harel; Myriam Létourneau; Vincent Finnerty; Alain Fournier; Jocelyn Dupuis; Jean N DaSilva Journal: Am J Nucl Med Mol Imaging Date: 2019-10-15
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