title: Intravitreal injection of (99)Tc-MDP inhibits the development of laser-induced choroidal neovascularization in rhesus monkeys.
abstract: BACKGROUND
  The aim of this study was to investigate the safety and efficacy of intravitreal injection of (99)Tc-MDP, a decay product of (99m)Tc-MDP, on the development of laser-induced choroidal neovascularization (CNV) in rhesus monkeys.
  
  
  METHODS
  Experimental CNV was induced by argon laser with a small high-energy laser spot. Monkeys were given 50 μL of (99)Tc-MDP at a concentration of 0.005 μg/mL (n = 6) or 0.01 μg/mL (n = 6) by intravitreal injection once a week immediately after laser injury for a period of 56 days. Control animals were treated with the same volume of PBS (n = 6) in the same way. Eyes were monitored by ophthalmic examination, color fundus photography, fluorescence fundus angiography (FFA), optical coherence tomography (OCT) and histology. Incidences of grade 4 CNV lesions as well as the leakage areas of grade 4 CNVs on the late-phase of fluorescein angiograms were measured in a standardized, randomized and masked fashion fortnightly. The maximum widths and heights of grade 4 CNVs were also calculated by histology at the end of the experiment. Toxicity of (99)Tc-MDP on the retina was evaluated by electroretinogram (ERG) and histologic analysis.
  
  
  RESULTS
  (99)Tc-MDP reduced the incidences of grade 4 CNVs by 33.33 % and 39.40 % in the 0.005 μg/mL and 0.01 μg/mL groups, respectively, compared with the PBS group on day 28 (P < 0.05; n = 6). The leakage areas of grade 4 CNVs were smaller in the 0.005 μg/mL (0.7136 ± 0.0283 mm(2), p <0.01; n = 6) and 0.01 μg/mL (0.4351 ± 0.0349 mm(2), p < 0.01; n = 6) groups than those in the PBS control group (0.9373 ± 0.0455 mm(2); n = 6) in a dose-dependent manner on day 28. OCT and histology also showed that the sizes of CNVs were smaller in the (99)Tc-MDP treated groups than those in the PBS group. Although intravitreal injection of (99)Tc-MDP led to mild inflammatory reaction in the anterior chamber, histology and ERG findings demonstrated that (99)Tc-MDP did not cause any change in histological structure or function of the retina (p>0.05).
  
  
  CONCLUSIONS
  Intravitreal injection of (99)Tc-MDP can inhibit the development of laser-induced CNV without toxic effect on retina, suggesting that (99)Tc-MDP has therapeutic potential for CNV related diseases.
authors.affiliation: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, 54 South Xianlie Road, Guangzhou, 510060, China.
authors.forename: Kunbei
authors.initials: K
authors.lastname: Lai
authors.forename: Chenjin
authors.initials: C
authors.lastname: Jin
authors.forename: Shu
authors.initials: S
authors.lastname: Tu
authors.forename: Yunfan
authors.initials: Y
authors.lastname: Xiong
authors.forename: Rui
authors.initials: R
authors.lastname: Huang
authors.forename: Jian
authors.initials: J
authors.lastname: Ge
mesh_terms: D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects; D020256:Choroidal Neovascularization / Q000145:classification / Q000473:pathology / Q000517:prevention & control*; D004195:Disease Models, Animal; D004596:Electroretinography; D005260:Female; D005451:Fluorescein Angiography; D058449:Intravitreal Injections; D053685:Laser Therapy; D054018:Lasers, Excimer; D008253:Macaca mulatta; D008297:Male; D019275:Radiopharmaceuticals / Q000008:administration & dosage / Q000627:therapeutic use*; D013669:Technetium Tc 99m Medronate / Q000008:administration & dosage / Q000627:therapeutic use*; D041623:Tomography, Optical Coherence
chemical_list: D019275:Radiopharmaceuticals; D013669:Technetium Tc 99m Medronate