Manganese-enhanced MRI of human choroidal melanoma xenografts

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).

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 MnCl(2), 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 MnCl(2) exposure and washing.

In vitro, spheroids exposed to MnCl(2) retained sufficient Mn(2+) to demonstrate contrast enhancement during MEMRI. In vivo, injection of MnCl(2) 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).

The present identification of regions of enhanced Mn(2+) 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.