Purchase this article with an account.
S. Li, X. Liu, S. A. Molokhia, E.-K. Jeong; 19F MR Study of Ocular Clearance of a Corticosteroid After Subconjunctival and Intravitreal Injections. Invest. Ophthalmol. Vis. Sci. 2010;51(13):2449.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Corticosteroids such as triamcinolone acetonide have been used in the treatment of macular edema and uveitis. Understanding the clearance of these drugs after subconjunctival and intravitreal injections can help clinicians improve the dosing regimen for effective therapy. In the present study, 19F MR (fluorine magnetic resonance) was used to noninvasively monitor the clearance of triamcinolone acetonide phosphate (TAP) in the rabbit eye after subconjunctival and intravitreal injections in vivo and postmortem with a clinical scanner.
MR experiments were performed on a Siemens 3T Trio clinical MRI system with New Zealand white rabbits in vivo and postmortem. A homebuilt 1.5-inch diameter surface coil was tuned to 115.93 MHz to acquire the 19F signal. After the subconjunctival and intravitreal injections of 0.1 mL 0.09 M TAP (mixed with manganese ethylenediaminetetraacetate, MnEDTA), dynamic 19F spectra were obtained using a FID pulse sequence. The MR data were acquired at 0, 0.5, 1, 2, 4, 8, 12 and 24 hr after the injection. The injection site in the vitreous was determined using the MnEDTA and 1H MRI.
The 19F MR results show that the elimination half-lives of TAP in the eye after subconjunctival injection were 0.5 hr in vivo and 6.0 hr postmortem. The half-lives of TAP after intravitreal injection were 8 hr in vivo and 17 hr postmortem. The shorter in vivo half-life after subconjunctival injection relative to that of intravitreal injection was believed to be due to the distance of the injection site from the clearance site. The difference in the elimination half-lives of TAP in vivo and postmortem suggests the importance of fluid dynamics in the eye and blood circulation around the eyes to TAP clearance, particularly after subconjunctival injection. By comparing the in vivo and postmortem data, the elimination rate constants associated with clearance were estimated to be 0.05/hr for intravitreal injection and 1.3/hr for subconjunctival injection, corresponding to half-lives of 14 and 0.5 hr, respectively.
A whole-body clinical MRI system was modified to perform 19F MR with a FID pulse sequence for noninvasive ocular pharmacokinetic studies. The present animal study has demonstrated the feasibility of noninvasively monitoring the clearance of fluorine-containing drugs after ocular delivery using 19F MR, which may allow the eventual use of this method to study ocular pharmacokinetics in human.
This PDF is available to Subscribers Only