September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
A novel rabbit model of intraarterial chemotherapy / ophthalmic artery chemosurgery
Author Affiliations & Notes
  • Anthony B Daniels
    Ophthalmology and Visual Sciences, Cancer Biology, and Radiation Oncology, Vanderbilt University Medical Center, Nashville, Tennessee, United States
    Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, Tennessee, United States
  • Michael T. Froehler
    Cerebrovascular Program, Vanderbilt University Medical Center, Nashville, Tennessee, United States
  • Janene M. Pierce
    Ophthalmology and Visual Sciences, Vanderbilt Eye Institute, Nashville, Tennessee, United States
  • Amy Nunnally
    Surgical Research, Vanderbilt University Medical Center, Nashville, Tennessee, United States
  • Thomas M. Bridges
    Pharmacology, Vanderbilt University, Nashville, Tennessee, United States
  • Debra L. Friedman
    Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee, United States
    Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, Tennessee, United States
  • Ann Richmond
    Tennessee Valley Healthcare System, Department of Veterans Affairs, Nashville, Tennessee, United States
    Cancer Biology, Vanderbilt University, Nashville, Tennessee, United States
  • Footnotes
    Commercial Relationships   Anthony Daniels, None; Michael Froehler, None; Janene Pierce, None; Amy Nunnally, None; Thomas Bridges, None; Debra Friedman, None; Ann Richmond, None
  • Footnotes
    Support  Knights Templar Eye Foundation Career Starter Grant; In addition, the project described was supported by the National Center for Research Resources, Grant UL1 RR024975-01, and is now at the National Center for Advancing Translational Sciences, Grant 2 UL1 TR000445-06.
Investigative Ophthalmology & Visual Science September 2016, Vol.57, 3667. doi:
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      Anthony B Daniels, Michael T. Froehler, Janene M. Pierce, Amy Nunnally, Thomas M. Bridges, Debra L. Friedman, Ann Richmond; A novel rabbit model of intraarterial chemotherapy / ophthalmic artery chemosurgery. Invest. Ophthalmol. Vis. Sci. 2016;57(12):3667.

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

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Abstract

Purpose : No small animal models of ophthalmic artery chemosurgery (OAC) exist. We have developed a rabbit model of OAC in order to be able to test the efficacy and toxicity of various drugs in a preclinical model system.

Methods : Femoral cut down was performed and the artery accessed and sheath placed. A microcatheter was advanced under fluoroscopic guidance and internal carotid artery (ICA) and external carotid artery (ECA) vasculature were interrogated angiographically to determine whether the ocular supply was via the internal or the external ophthalmic artery (OA). Ocular vascular supply was also confirmed by selective intraarterial fluorescein injection with retinal angiography as well as by selective vascular casting followed by ex vivo microCT. For chemotherapy treatments, the microcatheter was advanced up to the os of the dominant OA and 0.4 mg/kg melphalan was injected in a pulsatile fashion. For PK studies, following melphalan infusion, serial vitreous taps were obtained from both the treated and contralateral eye as well as from plasma up to 6 hours post treatment, and drug concentrations were measured by mass spectrometry. Eyes were subsequently harvested and in situ imaging mass spectrometry (IMS) was performed to measure intraretinal melphalan levels.

Results : Angiography demonstrated several vascular variations, with ocular blood supply arising from either the internal OA off the ICA, from the external OA off the ECA, or from both, but was consistent between the two eyes of a given rabbit. This was confirmed by selective arterial fluorescein angiography as well as vascular casting followed by ex vivo microCT. Eye histopathology did not demonstrate retinal emboli or vascular damage. PK studies demonstrated a rapid rise in vitreous melphalan levels with a peak between 30-60 minutes post injection, followed by first order elimination with a half life of 1.6 hours. This was prolonged compared to the plasma half life of 1.1 hours, consistent with intraocular accumulation. In situ IMS demonstrated intraretinal as well as vitreous melphalan accumulation in the treated eyes.

Conclusions : OAC can be safely and reliably performed in a rabbit model system. There are several variations in rabbit ocular vascular supply, but ophthalmic arteries could be successfully accessed in all rabbits. PK studies and IMS demonstrate vitreous and retinal accumulation of melphalan in this model.

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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