Positron Emission Tomography for the Development and Characterization of Corneal Permanence of Ophthalmic Pharmaceutical Formulations.
This work is aimed at describing the utility of positron emission tomography/computed tomography (PET/CT) as a noninvasive tool for pharmacokinetic studies of biopermanence of topical ocular formulations.



The corneal biopermanence of a topical ophthalmic formulation containing gellan gum and kappa carragenan (0.82% wt/vol) labeled with 18Fluorine (18F) radiotracers (18F-FDG and 18F-NaF) was evaluated by using a dedicated small-animal PET/CT, and compared with the biopermanence of an aqueous solution labeled with the same compounds. Regions of interest (ROIs) were manually drawn on the reconstructed PET images for quantifying the radioactivity concentration in the eye. The biopermanence of the formulations was determined by measuring the radioactivity concentration at different times after topical application. Additionally, cellular and ex vivo safety assays were performed to assess the safety of the performed procedures.



Differences were observed in the ocular pharmacokinetics of the two formulations. After 1.5 hours of contact, 90% of the hydrogel remained in the ocular surface, while only 69% of the control solution remained. Furthermore, it was observed that flickering had a very important role in the approach of the trial. The application of 18F-FDG in the eye was neither irritating nor cytotoxic for human corneal epithelial cells.



The use of small-animal PET and 18F radiotracers in ocular pharmacokinetics of ophthalmic formulations is feasible and could be a safe method for future ocular pharmacokinetic studies in humans.
Pharmacy and Pharmaceutical Technology Department and Industrial Pharmacy Institute, Faculty of Pharmacy, University of Santiago de Compostela (USC), Campus Vida, Santiago de Compostela, Spain 2Pharmacy Department, Xerencia de Xestión Integrada de Santiago de Compostela (SERGAS), Travesía Choupana s/n Santiago de Compostela, Spain 3Molecular Imaging Group, Radiology Deptartment, Universidade de Santiago de Compostela (USC) and Health Research Institute of Santiago de Compostela (IDIS), R/ San Francisco s/n, Santiago de Compostela, Spain 4Clinical Pharmacology Group, University Hospital, Santiago de Compostela (CHUS), Universidade de Santiago de Compostela, Health Research Institute of Santiago de Compostela (IDIS), Travesía da Choupana s/n Santiago de Compostela, Spain.
Anxo
A
Fernández-Ferreiro
Molecular Imaging Group, Radiology Deptartment, Universidade de Santiago de Compostela (USC) and Health Research Institute of Santiago de Compostela (IDIS), R/ San Francisco s/n, Santiago de Compostela, Spain.
Jesús
J
Silva-Rodríguez
Pharmacy and Pharmaceutical Technology Department and Industrial Pharmacy Institute, Faculty of Pharmacy, University of Santiago de Compostela (USC), Campus Vida, Santiago de Compostela, Spain.
Francisco Javier
FJ
Otero-Espinar
Pharmacy Department, Xerencia de Xestión Integrada de Santiago de Compostela (SERGAS), Travesía Choupana s/n Santiago de Compostela, Spain 4Clinical Pharmacology Group, University Hospital, Santiago de Compostela (CHUS), Universidade de Santiago de Compostela, Health Research Institute of Santiago de Compostela (IDIS), Travesía da Choupana s/n Santiago de Compostela, Spain.
Miguel
M
González-Barcia
Pharmacy Department, Xerencia de Xestión Integrada de Santiago de Compostela (SERGAS), Travesía Choupana s/n Santiago de Compostela, Spain 4Clinical Pharmacology Group, University Hospital, Santiago de Compostela (CHUS), Universidade de Santiago de Compostela, Health Research Institute of Santiago de Compostela (IDIS), Travesía da Choupana s/n Santiago de Compostela, Spain.
María Jesús
MJ
Lamas
Molecular Imaging Group, Radiology Deptartment, Universidade de Santiago de Compostela (USC) and Health Research Institute of Santiago de Compostela (IDIS), R/ San Francisco s/n, Santiago de Compostela, Spain 5Nuclear Medicine Department and Molecular Imaging Group, University Hospital, Santiago de Compostela (CHUS), Universidade de Santiago de Compostela (USC), Health Research Institute of Santiago de Compostela (IDIS), Travesía da Choupana s/n Santiago de Compostela, Spain.
Alvaro
A
Ruibal
Pharmacy and Pharmaceutical Technology Department and Industrial Pharmacy Institute, Faculty of Pharmacy, University of Santiago de Compostela (USC), Campus Vida, Santiago de Compostela, Spain.
Andrea
A
Luaces-Rodriguez
Clinical Neurosciences Research Laboratory, University Hospital, Santiago de Compostela (CHUS), Universidade de Santiago de Compostela, Health Research Institute of Santiago de Compostela (IDIS), Travesía da Choupana s/n Santiago de Compostela, Spain.
Alba
A
Vieites-Prado
Clinical Neurosciences Research Laboratory, University Hospital, Santiago de Compostela (CHUS), Universidade de Santiago de Compostela, Health Research Institute of Santiago de Compostela (IDIS), Travesía da Choupana s/n Santiago de Compostela, Spain.
Tomas
T
Sobrino
Molecular Imaging Group, Radiology Deptartment, Universidade de Santiago de Compostela (USC) and Health Research Institute of Santiago de Compostela (IDIS), R/ San Francisco s/n, Santiago de Compostela, Spain 5Nuclear Medicine Department and Molecular Imaging Group, University Hospital, Santiago de Compostela (CHUS), Universidade de Santiago de Compostela (USC), Health Research Institute of Santiago de Compostela (IDIS), Travesía da Choupana s/n Santiago de Compostela, Spain.
Michel
M
Herranz
Molecular Imaging Group, Radiology Deptartment, Universidade de Santiago de Compostela (USC) and Health Research Institute of Santiago de Compostela (IDIS), R/ San Francisco s/n, Santiago de Compostela, Spain.
Lara
L
García-Varela
Pharmacy and Pharmaceutical Technology Department and Industrial Pharmacy Institute, Faculty of Pharmacy, University of Santiago de Compostela (USC), Campus Vida, Santiago de Compostela, Spain.
José
J
Blanco-Mendez
Ophthalmology Department, Xerencia de Xestión Integrada de Santiago de Compostela (SERGAS), Travesía Choupana s/n Santiago de Compostela, Spain.
María
M
Gil-Martínez
Obesidomic Group, Health Research Institute of Santiago de Compostela (IDIS), Travesía da Choupana s/n Santiago de Compostela, Spain.
María
M
Pardo
Molecular Imaging Group, Radiology Deptartment, Universidade de Santiago de Compostela (USC) and Health Research Institute of Santiago de Compostela (IDIS), R/ San Francisco s/n, Santiago de Compostela, Spain.
Alexis
A
Moscoso
Galician PET Radiopharmacy Unit, Galaria, University Hospital, Santiago de Compostela (CHUS), Travesía Choupana s/n Santiago de Compostela, Spain.
Santiago
S
Medín-Aguerre
Molecular Imaging Group, Radiology Deptartment, Universidade de Santiago de Compostela (USC) and Health Research Institute of Santiago de Compostela (IDIS), R/ San Francisco s/n, Santiago de Compostela, Spain 10Medical Physics Department, University Hospital, Santiago de Compostela (CHUS), Travesía Choupana s/n Santiago de Compostela, Spain.
Juan
J
Pardo-Montero
Molecular Imaging Group, Radiology Deptartment, Universidade de Santiago de Compostela (USC) and Health Research Institute of Santiago de Compostela (IDIS), R/ San Francisco s/n, Santiago de Compostela, Spain 5Nuclear Medicine Department and Molecular Imaging Group, University Hospital, Santiago de Compostela (CHUS), Universidade de Santiago de Compostela (USC), Health Research Institute of Santiago de Compostela (IDIS), Travesía da Choupana s/n Santiago de Compostela, Spain.
Pablo
P
Aguiar
D000818:Animals; D002351:Carrageenan / Q000493:pharmacokinetics; D003315:Cornea / Q000187:drug effects / Q000378:metabolism*; D016503:Drug Delivery Systems / Q000379:methods; D019788:Fluorodeoxyglucose F18 / Q000008:administration & dosage / Q000633:toxicity; D006801:Humans; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000737:chemistry / Q000493:pharmacokinetics*; D008297:Male; D009883:Ophthalmic Solutions / Q000493:pharmacokinetics*; D011135:Polysaccharides, Bacterial / Q000493:pharmacokinetics; D000072078:Positron Emission Tomography Computed Tomography; D019275:Radiopharmaceuticals / Q000008:administration & dosage / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley
D009883:Ophthalmic Solutions; D011135:Polysaccharides, Bacterial; D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; C048288:gellan gum; D002351:Carrageenan