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R. D. Braun, K. S. Vistisen; Quantification of Growth of Human Choroidal Melanoma Xenografts Using High-Frequency Ultrasound. Invest. Ophthalmol. Vis. Sci. 2007;48(13):4791.
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In current rodent xenograft models of human uveal melanoma, it is not possible to continuously monitor primary tumor growth, because immunocompromised animals cannot be readily moved to standard imaging equipment outside the housing facility. The development of a hand-held, high-resolution, high-frequency ultrasound (HF-US) system for small animal research (Model MHF-1, E-Technologies, Inc., Bettendorf, IA) has made it feasible to attempt to repeatedly image tumor growth in the eyes of nude rats. The purpose of this study was to test the hypothesis that growth of primary orthotopic human choroidal melanoma xenografts can be quantified noninvasively in the same rat over time using HF-US.
Orthotopic xenografts were grown in 10 eyes by implanting human choroidal melanoma C918 spheroids into the suprachoroidal space of nude, athymic WAG/Nij-rnu rats. Every 5 to 7 days thereafter for up to 3 weeks, rats were anesthetized with ketamine/xylazine in a laminar flow hood. HF-US images of the tumor-bearing eyes were captured at 250 µm intervals. Tumor areas were measured on each image, and the areas were numerically integrated to calculate a tumor volume. Tumor volumes were also estimated from serial sections of the paraffin-embedded eyes of three rats.
Tumors could be visualized as hyperechoic regions in the superior portion of the tumor-bearing eye in the HF-US images from all 10 rats. There were no episodes of infection or death during the study. Tumor volume as determined from the HF-US images increased as a function of time after implantation in all 10 rats, indicative of tumor growth. Volumes determined from histology were 3.13, 4.33, and 7.87 mm3 compared to 3.19, 4.65, and 6.18 mm3 determined from HF-US.
HF-US is a safe, practical method to estimate tumor volume in the same nude rat over time, without removing the animal from the housing facility. This technique can be used to perform standard tumor growth delay studies in this orthotopic xenograft model of human choroidal melanoma, greatly reducing the number of animals required to test new therapies.
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