Angiography of fluoresceinated anti-vascular endothelial growth factor antibody and dextrans in experimental choroidal neovascularization.
OBJECTIVE
To determine if anti-vascular endothelial growth factor antibody and a range of dextrans with varying diffusion radii and molecular weights are permeable through experimental choroidal neovascularization (CNV).


METHODS
Choroidal neovascularization was induced in 10 cynomolgus monkey retinas by means of argon laser injury. Digital fundus fluorescein angiograms were performed with fluorescein sodium, fluoresceinated IgG antibodies (anti-vascular endothelial growth factor and a control antibody), and fluoresceinated dextrans with molecular weights of 4, 20, 40, 70 and 150 kd. The 40- and 70-kd dextrans straddle the effective diffusion radius of IgG. For each reagent, early and late angiograms were performed in a standardized fashion, with follow-up images obtained to monitor residual fluorescence.


RESULTS
Perfusion of retinal vessels and choroidal vasculature was seen with all reagents. Fluorescein and 4- and 20-kd dextran leaked rapidly from the CNV within the first minute. Angiography with the use of 40-kd dextran and fluoresceinated antibody, either anti-vascular endothelial growth factor or control IgG, showed fluorescence within the CNV that increased during the first 1 to 5 hours, with mild leakage from the CNV. By 24 hours, fluorescence in the CNV was minimal, although in some cases persistent fluorescence in the surrounding tissue was evident up to 2 weeks. The 70-kd dextran showed fluorescence within the CNV and leakage in 1 of 3 eyes. The 150-kd dextran showed fluorescence within the CNV but did not demonstrate leakage.


CONCLUSIONS
Fluoresceinated antibodies and dextran with smaller effective diffusion radii showed CNV perfusion and leakage. Dextrans with larger effective diffusion radii (70 kd and 150 kd) perfused into CNV but did not show leakage consistently.


CONCLUSIONS
Determining the permeablity of antibodies and molecules of similar size through CNV can help ascertain the feasibility of using intravenously administered antibodies against angiogenic growth factors as a future treatment for choroidal neovascularization.
Tolentino
M J
MJ
Retina Service, Massachusetts Eye and Ear Infirmary, Boston 02114, USA.
Husain
D
D
Theodosiadis
P
P
Gragoudas
E S
ES
Connolly
E
E
Kahn
J
J
Cleland
J
J
Adamis
A P
AP
Cuthbertson
A
A
Miller
J W
JW
D000818:Animals; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics*; D002199:Capillary Permeability; D002829:Choroid / Q000098:blood supply / Q000473:pathology; D020256:Choroidal Neovascularization / Q000378:metabolism* / Q000473:pathology; D003911:Dextrans / Q000493:pharmacokinetics*; D004195:Disease Models, Animal; D016228:Endothelial Growth Factors / Q000276:immunology*; D005451:Fluorescein Angiography; D016650:Fluorescein-5-isothiocyanate / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D007275:Injections, Intravenous; D008222:Lymphokines / Q000276:immunology*; D008252:Macaca fascicularis; D008863:Microspheres; D008970:Molecular Weight; D012171:Retinal Vessels / Q000378:metabolism / Q000473:pathology; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D000911:Antibodies, Monoclonal; D003911:Dextrans; D016228:Endothelial Growth Factors; D008222:Lymphokines; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; C015219:fluorescein isothiocyanate dextran; D016650:Fluorescein-5-isothiocyanate