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P. T. Khaw, H. Fadda, A. Khalili, H. G. Parkes, J. S. Ellis, D. J. Paull, S. Brocchini; Magnetic Resonance Imaging of the Rabbit Eye to Determine the Presence of Bevacizumab (Avastin) Tablet in the Posterior Sclera. Invest. Ophthalmol. Vis. Sci. 2010;51(13):2450.
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© ARVO (1962-2015); The Authors (2016-present)
Angiogenesis underlies the pathogenesis of many blinding diseases. However, anti-angiogenic medicines (eg. bevacizumab and ranibizumab) would clear rapidly if injected into the subconjunctiva. We are developing a bevacizumab tissue tablet to provide a more sustained release profile (ARVO2009 #5992). We have begun to evaluate the potential to use magnetic resonance imaging (MRI) to determine the real time pharmacokinetics of our bevacizumab tissue tablet in an ex-vivo experiment with rabbit eyes.
A tissue tablet incorporating bevacizumab (Avastin, 1.25mg) was fabricated. Rabbit eyes were obtained within 24 hours of sacrifice. In the first group (n=4), a 2-3 mm incision was made at the limbus, a conjunctival pocket formed and a bevacizumab tablet implanted 5-7 mm behind the limbus, followed by incision closure with 2 stitches (Vicryl 6.0). In the second group (n=4), bevacizumab (1.25mg, 50µL) was injected at a similar position. Images of the eyes were obtained 24 hours post injection/implantation using a Varian 9.4 Tesla VNMRS MRI scanner (Varian Inc, Palo Alto, USA).
The bevacizumab injection disappeared within 24 hours and could not be detected at the site of injection. The bevacizumab tablet, however, was still readily detectable at the 24 hour time point. MRI using a gradient echo multi slice experiment TR 1500 ms and TE 16 ms was carried out (see figure) with a field of view 90x45 mm and a matrix size of 512x256, giving an in-plane resolution of 175 µm and a slice thickness of 500 µm.
MRI is potentially an ideal method for the non-invasive detection and monitoring of our bevacizumab tablets located within the rabbit eye. Labeling work is ongoing so that the released bevacizumab can be monitored as it flows from the tablet into the ocular tissue.
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