Abstract 3929: Orthotopic human choroidal melanoma model characterization with bioluminescence and magnetic resonance imaging for therapeutic efficacy evaluation
Authors: Chunta John L. , Baugher Meridith , Lister Deanne , Trachet Erin , Guley Kevin P. , Bull Chris , Wise Scott , Leopold Wilbur R. , McConville Patrick 
Published: May 2015

BACKGROUND: Intraocular melanomas in the West represents 70% of all primary eye cancers with a mortality rate greater than 50%. Current treatment options include enucleation, plaque radiotherapy, and proton beam radiotherapy. While enucleation is a highly invasive surgical procedure that removes the eye, the side effects of the two different radiotherapies include cataracts, retinopathy, cystoid macular edema, and secondary retinal detachment. Due to the relatively protected nature of the eye within the orbit, most topical treatment applications are precluded and systemic treatments increases the chance and incidence of off-target side effects. Up and coming targeted therapies that may not be constrained by such limitations require a non-invasive, imaging-relevant model in order to evaluate their efficacy. Therefore, the aim of this study was to characterize the imaging of orthotopic luc-enabled OCM-1 human choroidal melanoma tumors using bioluminescence imaging (BLI) and magnetic resonance imaging (MRI) for future use in anti-cancer drug efficacy testing.

MATERIALS & METHODS: Human choroidal melanoma cells were modified to express luciferase. 8-12 week old female NIH-Foxn1rnu rats were implanted in the suprachoroidal space with OCM-1-luc tumor spheroids on Day 0. BLI and MRI imaging was performed every 5-7 days starting at Day 7 after implantation of the OCM-1-luc spheroids until animals reached a moribund state to monitor disease progression. For BLI, animals were injected with 150mg/kg luciferin, anesthetized with isoflurane in air and imaged at 10 minutes following luciferin administration. Anatomical MRI was performed using a gradient-echo pulse sequence on a 7T MRI system. After euthanasia, eyes were removed and preserved in formalin for histological analysis.

RESULTS & CONCLUSIONS: Animals tolerated the ocular tumor implant well. As a result of these efforts, we have successfully characterized the growth of orthotopic luc-enabled OCM-1 choroidal melanomas using both bioluminescence and magnetic resonance imaging. This provides a simple approach with which to monitor tumor growth and treatment response in a highly efficient way which should allow a high daily animal throughput. These promising results will serve as a solid foundation with which dose routes and levels of anti-cancer drugs can be optimized and their efficacy evaluated with noninvasive imaging.

Citation Format: John L. Chunta, Meridith Baugher, Deanne Lister, Erin Trachet, Kevin P. Guley, Chris Bull, Scott Wise, Wilbur R. Leopold, Patrick McConville. Orthotopic human choroidal melanoma model characterization with bioluminescence and magnetic resonance imaging for therapeutic efficacy evaluation. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3929. doi:10.1158/1538-7445.AM2014-3929