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Josh M. Rowe, Sue Kanaly, Yan Hai, Jinsong Ni; MALDI-MS Imaging of a Peptide Drug Candidate in Rabbit and Monkey Eyes following Intravitreal Injection. Invest. Ophthalmol. Vis. Sci. 2011;52(14):1349.
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Matrix-assisted laser desorption ionization-mass spectrometry imaging (MALDI-MS imaging) is an emerging technique that is being used to study the distribution of biological molecules and xenobiotics in tissue samples. To our knowledge, MALDI-MS imaging has never been used to study the distribution of xenobiotics in fixed, paraffin embedded ocular tissue samples. The objective of this study was to utilize MALDI-MS imaging to study the distribution of peptide drug candidate (Peptide A) in fixed paraffin embedded eyes of rabbit and monkey, and to compare drug distribution with pathology findings.
Rabbits and monkeys were treated with a single intravitreal injection of a solution of Peptide A of up to 5 mg on day 1. At day 3 and 14, animals were sacrificed, and eyes were enucleated and treated according to a standard fixation (Davidson’s) and paraffin embedding protocol. Sections from whole fixed paraffin embedded eyes were prepared for MALDI-MS imaging, and analyzed using a Waters Synapt G1 mass spectrometer. Experiments to optimize and evaluate method performance and reproducibility and to evaluate the effects of various sample collection and preparation procedures were performed. Standard pathology evaluation of H&E stained sections was performed.
A representative MALDI-MS image of Peptide A in rabbit eye is shown in Figure 1. Fixation and paraffin embedding procedure did not alter drug levels in the retina compared to frozen. There appeared to be good correlation between drug levels and drug induced lesions in retina of monkey and rabbit.
Our results demonstrated for the first time that MALDI-MS imaging can utilized to study the distribution of a peptide drug in fixed paraffin embedded eyes. There was good correlation between drug levels and pathology findings.
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