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Manganese-Enhanced MRI of Human Choroidal Melanoma Xenografts

¹From the Department of Anatomy and Cell Biology, Wayne State University School of Medicine, the ²Barbara Ann Karmanos Cancer Institute, and the ³Kresge Eye Institute, Wayne State University, Detroit, Michigan.

PURPOSE. To test the hypothesis that the structure and function of an experimental human choroidal melanoma xenograft and neighboring non–tumor-bearing retina can be simultaneously assessed by using manganese-enhanced MRI (MEMRI).

METHODS. Spheroids grown from the human choroidal melanoma cell line C918 were implanted in the superior suprachoroidal space of 11 WAG/Nij-rnu nude rats. Two weeks later, MRI data were collected 4 hours after intraperitoneal injection of saline or MnCl₂, an MRI contrast agent that can act as a biomarker of cellular demand for ions, such as calcium. The following parameters were measured: (1) tumor signal intensity, (2) inner and outer retinal signal intensity in non–tumor-bearing inferior retina, and (3) whole and inner retinal thickness of inferior retina. Separate MEMRI experiments were performed on spheroids in vitro after MnCl₂ exposure and washing.

RESULTS. In vitro, spheroids exposed to MnCl₂ retained sufficient Mn²⁺ to demonstrate contrast enhancement during MEMRI. In vivo, injection of MnCl₂ resulted in a 30% increase in tumor signal intensity compared with tumors in rats injected with saline (P < 0.05). In inferior retina of tumor-bearing eyes, outer retinal signal intensity increased by 17% relative to a similar region in control eyes (P < 0.05), but there was no change in the inferior inner retinal intensity. Total retinal thickness of the inferior retina in the tumor-bearing eyes increased by 8%, compared with that in the non–tumor-bearing eyes (P < 0.05).

CONCLUSIONS. The present identification of regions of enhanced Mn²⁺ uptake in choroidal melanoma and a somewhat unexpected edema and increased outer retinal ion demand in neighboring non–tumor-bearing retina highlights MEMRI as a potentially powerful method for noninvasively monitoring tumor progression and treatment response and efficacy.

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