Radiosynthesis and assessment of ocular pharmacokinetics of (124)I-labeled chitosan in rabbits using small-animal PET.
OBJECTIVE
The polysaccharide chitosan is a unique material for the design of ocular drug-delivery vehicles. The aim of this study was to radiolabel chitosan with iodine-124 ((124)I) for measurement of ocular pharmacokinetics in rabbits using small-animal positron emission tomography (PET).


METHODS
Crl:CHBB (HM) rabbits received one drop (35 µL) of either a formulation containing chitosan (0.5%, w/v) spiked with (124)I-labeled chitosan ([(124)I]chitosan) (n = 4) or a control solution of sodium [(124)I]iodide in buffer (n = 2) in the conjunctival sac of the right eye. Radioactivity distribution in the head region was measured at five different time points between 0 and 22 h after topical application. Regions of interest were manually defined in the reconstructed PET images, and activity concentration was quantified as percent applied dose (AD) per cubic centimeter tissue.


RESULTS
Clear differences were observed in the ocular pharmacokinetics of the two formulations. At 3 h after application, ocular activity uptake was 0.5 ± 0.1%AD/cc for sodium [(124)I]iodide, compared to 4.7 ± 5.3%AD/cc for the [(124)I]chitosan formulation.


CONCLUSIONS
We were able to show that ocular pharmacokinetics of (124)I-labeled ophthalmic formulations can be measured with small-animal PET and that [(124)I]chitosan had approximately a 2-fold increased ocular retention through the study period compared to sodium [(124)I]iodide.
Kuntner
Claudia
C
Molecular Medicine, AIT Austrian Institute of Technology GmbH, 2444 Seibersdorf, Austria. claudia.kuntner@ait.ac.at
Wanek
Thomas
T
Hoffer
Martin
M
Dangl
Daniel
D
Hornof
Margit
M
Kvaternik
Herbert
H
Langer
Oliver
O
D000818:Animals; D019540:Area Under Curve; D048271:Chitosan / Q000138:chemical synthesis* / Q000493:pharmacokinetics*; D005123:Eye / Q000000981:diagnostic imaging*; D005260:Female; D007457:Iodine Radioisotopes; D007553:Isotope Labeling; D049268:Positron-Emission Tomography; D011817:Rabbits; D013997:Time Factors
D007457:Iodine Radioisotopes; D048271:Chitosan