September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
Non-invasive in vivo fluorescence imaging method enables ocular pharmacokinetics assessment of intravitreally administered biologics in rabbits
Author Affiliations & Notes
  • Viral Kansara
    Novartis Institutes for Biomedical Research, Cambridge, Massachusetts, United States
  • Debby Long
    Novartis Institutes for Biomedical Research, Cambridge, Massachusetts, United States
  • Timothy Drew
    Novartis Institutes for Biomedical Research, Cambridge, Massachusetts, United States
  • Farid Sari-Sarraf
    Novartis Institutes for Biomedical Research, Cambridge, Massachusetts, United States
  • Radhika Sharma
    Novartis Institutes for Biomedical Research, Cambridge, Massachusetts, United States
  • Hidetomo Imase
    Novartis Institutes for Biomedical Research, Cambridge, Massachusetts, United States
  • Qiying Hu
    Novartis Institutes for Biomedical Research, Cambridge, Massachusetts, United States
  • Bruce D Jaffee
    Novartis Institutes for Biomedical Research, Cambridge, Massachusetts, United States
  • Footnotes
    Commercial Relationships   Viral Kansara, None; Debby Long, None; Timothy Drew, None; Farid Sari-Sarraf, None; Radhika Sharma, None; Hidetomo Imase, None; Qiying Hu, None; Bruce Jaffee, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science September 2016, Vol.57, 2209. doi:
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    • Get Citation

      Viral Kansara, Debby Long, Timothy Drew, Farid Sari-Sarraf, Radhika Sharma, Hidetomo Imase, Qiying Hu, Bruce D Jaffee; Non-invasive in vivo fluorescence imaging method enables ocular pharmacokinetics assessment of intravitreally administered biologics in rabbits. Invest. Ophthalmol. Vis. Sci. 2016;57(12):2209.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : The objective of this work was to develop and validate a non-invasive imaging method for studying the ocular pharmacokinetics (PK) of intravitreally administered drugs in rabbits. Traditional methods require sacrifice of rabbits to harvest and dissect eyes at each timepoint. We explored whether the non-invasive Maestro imaging system could reduce the number of rabbits required to obtain PK profiles of potential therapeutics.

Methods : Full length monoclonal antibody (150kD) or antigen-binding fragment (Fab) antibody (48kD) labeled with Alexa Fluor 750, were injected into the mid-vitreous of both eyes of Dutch belted rabbits under deep anesthesia (n=3 rabbits/ group). Eyes were imaged using the Maestro imaging system (which allows repetitive monitoring of fluorophore-tagged drugs in live rabbits) at 2, 4, 6, 8, 14, 17, and 21 days. The ocular terminal half-lives were calculated from the time-signal profile of fluorescence. The ocular pharmacokinetics of labeled antibodies was compared with in house, as well as, published literature obtained by traditional methods.

Results : The in vivo fluorescence imaging technique using the Maestro system enabled the detection of labeled antibodies up to 3 weeks after single doses of 5ug and 15ug, respectively. A monoexponential decay of the signals was observed for both injected biologics. The rate of ocular elimination of full length antibody was higher than that of Fab. The terminal half-life values were calculated to be 2.59 + 0.47 days and 3.81 + 1.03 days for full length antibody and Fab, respectively. These values are within a range of published half-life values using traditional method.

Conclusions : We have developed and validated a non-invasive fluorescence imaging method using the Maestro imaging system for assessing ocular PK in rabbits. This non-invasive technique is an effective way to measure the pharmacokinetics of biologics while greatly reducing the number of rabbits needed for ocular PK studies.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.

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