Anxo Fernández-Ferreiro1, Andrea Luaces-Rodríguez2, Pablo Aguiar3, Juan Pardo-Montero4, Miguel González-Barcia5, Lara García-Varela6, Michel Herranz7, Jesús Silva-Rodríguez6, María Gil-Martínez8, María A Bermúdez9, Alba Vieites-Prado10, José Blanco-Méndez2, María Jesús Lamas5, Francisco Gómez-Ulla11, Álvaro Ruibal12, Francisco Javier Otero-Espinar2, Francisco González11. 1. Department of Pharmacology, Pharmacy and Pharmaceutical Technology and Industrial Pharmacy Institute, Faculty of Pharmacy, University of Santiago de Compostela, Santiago de Compostela, Spain 2Pharmacy Department, Complejo Hospitalario Universitario de Santiago (SERGAS), Santiago de Compostela, Spain 3Molecular Imaging Group, Complejo Hospitalario Universitario de Santiago (SERGAS), Health Research Institute of Santiago de Compostela (IDIS), Santiago de Compostela, Spain 4Clinical Pharmacology Group, Complejo Hospitalario Universitario de Santiago (SERGAS), Health Research Institute of Santiago de Compostela (IDIS), Santiago de Compostela, Spain. 2. Department of Pharmacology, Pharmacy and Pharmaceutical Technology and Industrial Pharmacy Institute, Faculty of Pharmacy, University of Santiago de Compostela, Santiago de Compostela, Spain. 3. Molecular Imaging Group, Complejo Hospitalario Universitario de Santiago (SERGAS), Health Research Institute of Santiago de Compostela (IDIS), Santiago de Compostela, Spain 5Molecular Imaging Group, Department of Radiology, Faculty of Medicine, University of Santiago de Compostela, Spain. 4. Molecular Imaging Group, Complejo Hospitalario Universitario de Santiago (SERGAS), Health Research Institute of Santiago de Compostela (IDIS), Santiago de Compostela, Spain 6Medical Physics Department, Complejo Hospitalario Universitario de Santiago (SERGAS), Santiago de Compostela, Spain. 5. Pharmacy Department, Complejo Hospitalario Universitario de Santiago (SERGAS), Santiago de Compostela, Spain 4Clinical Pharmacology Group, Complejo Hospitalario Universitario de Santiago (SERGAS), Health Research Institute of Santiago de Compostela (IDIS), Santiago de Compostela, Spain. 6. Molecular Imaging Group, Complejo Hospitalario Universitario de Santiago (SERGAS), Health Research Institute of Santiago de Compostela (IDIS), Santiago de Compostela, Spain. 7. Molecular Imaging Group, Complejo Hospitalario Universitario de Santiago (SERGAS), Health Research Institute of Santiago de Compostela (IDIS), Santiago de Compostela, Spain 7Galician PET Radiopharmacy Unit, Galaria, Complejo Hospitalario Universitario de Santiago (SERGAS), Santiago de Compostela, Spain. 8. Service of Ophthalmology, Complejo Hospitalario Universitario de Santiago (SERGAS), Health Research Institute of Santiago de Compostela (IDIS), Santiago de Compostela, Spain. 9. Department of Animal Biology, Vegetal Biology and Ecology, Faculty of Biology, University of A Coruña, A Coruña, Spain. 10. Clinical Neurosciences Research Laboratory, Complejo Hospitalario Universitario de Santiago (SERGAS), Health Research Institute of Santiago de Compostela (IDIS), Santiago de Compostela, Spain. 11. Service of Ophthalmology, Complejo Hospitalario Universitario de Santiago (SERGAS), Health Research Institute of Santiago de Compostela (IDIS), Santiago de Compostela, Spain 11Department of Surgery, University of Santiago de Compostela (CIMUS), Spain. 12. Molecular Imaging Group, Complejo Hospitalario Universitario de Santiago (SERGAS), Health Research Institute of Santiago de Compostela (IDIS), Santiago de Compostela, Spain 5Molecular Imaging Group, Department of Radiology, Faculty of Medicine, University of Santiago de Compostela, Spain 12Nuclear Medicine Department, Complejo Hospitalario Universitario de Santiago (SERGAS), Santiago de Compostela, Spain.
Abstract
Purpose: This work aimed at describing the time course of vitreous clearance through the use of positron emission tomography (PET) as a noninvasive tool for pharmacokinetic studies of intravitreal injection. Methods: The pharmacokinetic profile of intravitreal injections of molecules labeled with 18Fluorine (18F) was evaluated in adult Sprague Dawley rats by using a dedicated small-animal PET/computed tomography scanner. Different conditions were studied: three molecules radiolabeled with 18F (18F-FDG, 18F-NaF, and 18F-Choline), three volumes of intravitreal injections (7, 4, and 2 μL), and absence or presence of eye inflammation (uveitis). Results: Our results showed that there are significant pharmacokinetic differences among the radiolabeled molecules studied but not among the injected volumes. The presence or absence of uveitis was an important factor in vitreous clearance, since the elimination of the drug was clearly increased when this condition is present. Conclusions: Intravitreal pharmacokinetic studies based on the use of dedicated PET imaging can be of potential interest as noninvasive tools in ophthalmic drug development in small animals.
Purpose: This work aimed at describing the time course of vitreous clearance through the use of positron emission tomography (PET) as a noninvasive tool for pharmacokinetic studies of intravitreal injection. Methods: The pharmacokinetic profile of intravitreal injections of molecules labeled with 18Fluorine (18F) was evaluated in adult Sprague Dawley rats by using a dedicated small-animal PET/computed tomography scanner. Different conditions were studied: three molecules radiolabeled with 18F (18F-FDG, 18F-NaF, and 18F-Choline), three volumes of intravitreal injections (7, 4, and 2 μL), and absence or presence of eye inflammation (uveitis). Results: Our results showed that there are significant pharmacokinetic differences among the radiolabeled molecules studied but not among the injected volumes. The presence or absence of uveitis was an important factor in vitreous clearance, since the elimination of the drug was clearly increased when this condition is present. Conclusions: Intravitreal pharmacokinetic studies based on the use of dedicated PET imaging can be of potential interest as noninvasive tools in ophthalmic drug development in small animals.
Authors: Andrea Luaces-Rodríguez; Miguel González-Barcia; María José Blanco-Teijeiro; María Gil-Martínez; Francisco Gonzalez; Francisco Gómez-Ulla; María-Jesús Lamas; Francisco-Javier Otero-Espinar; Anxo Fernández-Ferreiro Journal: Pharmaceutics Date: 2018-05-29 Impact factor: 6.321
Authors: Maria Jesus Rodrigo; Amaya Pérez Del Palomar; Alberto Montolío; Silvia Mendez-Martinez; Manuel Subias; Maria Jose Cardiel; Teresa Martinez-Rincon; José Cegoñino; José Maria Fraile; Eugenio Vispe; José Antonio Mayoral; Vicente Polo; Elena Garcia-Martin Journal: Pharmaceutics Date: 2021-02-05 Impact factor: 6.321