Photodynamic therapy with PhotoPoint photosensitiser MV6401, indium chloride methyl pyropheophorbide, achieves selective closure of rat corneal neovascularisation and rabbit choriocapillaris.
OBJECTIVE
The new photosensitiser PhotoPoint MV6401, indium chloride methyl pyropheophorbide, was assessed as a possible ocular photodynamic therapy agent in a rat model of experimentally induced corneal neovascularisation and in choriocapillaris closure in the rabbit. Optimal drug and light activation parameters were determined.


METHODS
MV6401 (Miravant Pharmaceuticals, Inc, Santa Barbara, CA, USA) was activated at 664 nm using a DD3-0665 (Miravant Systems Inc) 0.5 W diode laser. Corneal neovascularisation in rats was induced using an N-heptanol technique. The evaluated drug dosages, light dosages, and post-injection activation times ranged from 0.01-0.1 micromol/kg, 5-25 J/cm(2), and 10-60 minutes, respectively. The efficacy of MV6401 on normal choriocapillaris and choroidal vessels was evaluated in rabbits with indirect ophthalmoscopy, fundus photography, fluorescein angiography, and histology. In rabbits, the evaluated drug dosages, light dosages, and post-injection activation times ranged from 0.025-0.25 micromol/kg, 3.3-20 J/cm(2), and 10 minutes, respectively.


RESULTS
In the rat corneal neovascularisation model, an optimal intravenous drug dosage of 0.075 micromol/kg was activated by a 20 J/cm(2) light dose at 10 minutes after drug administration, the results of which demonstrated early evidence of efficacy in ocular neovascularisation. In rabbits, closure of the normal choriocapillaris was selectively achieved at a drug dosage of 0.15 micromol/kg using light doses from 3.3 to 20 J/cm(2).


CONCLUSIONS
PhotoPoint MV6401 is a potent photosensitiser that demonstrates both efficacy and selectivity in experimental ocular models.
Ciulla
T A
TA
Department of Ophthalmology, Indiana University School of Medicine, Indianapolis, IN, USA. thomasciulla@yahoo.com
Criswell
M H
MH
Snyder
W J
WJ
Small
W
W
D000818:Animals; D002196:Capillaries / Q000187:drug effects; D002829:Choroid / Q000098:blood supply* / Q000187:drug effects / Q000473:pathology; D016510:Corneal Neovascularization / Q000188:drug therapy* / Q000473:pathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D005451:Fluorescein Angiography / Q000379:methods; D007204:Indium; D007275:Injections, Intravenous; D008297:Male; D009942:Organometallic Compounds / Q000008:administration & dosage*; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000008:administration & dosage*; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley
C453421:MV6401; D009942:Organometallic Compounds; D017319:Photosensitizing Agents; D007204:Indium; C020758:indium trichloride