Detecting hepatic metastases from ocular melanoma using MRI with a novel designed contrast agent

Abstract

 

Purpose

 

Despite successful local tumor control, one half of patients with ocular melanoma will die from hepatic metastases. The 10-year mortality rate in patients with undetected metastatic tumors is approximately 30%. Metastases-related deaths occur as long as 35 years after diagnosis of primary tumor. The mean survival time is around 12 to 14 months once the hepatic metastasis is diagnosed. The purpose of this study is to develop a novel contrast agent to detect early stage hepatic metastases from ocular melanoma.

 

Methods

 

The novel protein-based MRI contrast agent (ProCA) was designed and generated. ProCAs has more than 10 times high relaxivity than that of clinical MRI contrast agents. ProCAs also enhance liver with high dose efficiency and specificity. One eye of PEDF deficient homozygote mice (n=6) was inoculated with mouse melanoma cell B16LS9. At the 10th day after inoculation, the mice were injected with the novel contrast agent ProCA or a control protein through the tail vein, and imaged using a 4.7 T small animal MRI at 30 minutes post injection of the contrast agent. After imaging, the mice were sacrificed with their eyes and livers processed for histology and IHC staining for S100A and Ki67.

 

Results

 

Hepatic metastases could be detected with the novel protein-based contrast agent ProCA, but not with the control protein or without a contrast agent using MRI. Histology confirmed that the sizes of hepatic metastases which had been detected with MRI were less than 1 mm diameter. IHC identified that the melanoma marker S100A was expressed in the hepatic metastases. Hepatic metastases showed hypo-intensity with the T1 weighted spin echo sequence in vivo. The hypo-intense tumors also had been verified the lack of ProCA in tumors and strong fluorescence of fluorescently labeled ProCA in hepatic tissues using the Leicamz16FA microsystem in vitro.

 

Conclusions

 

The novel contrast agent, ProCA, is able to detect the <1 mm diameter metastatic ocular melanomas in the mouse liver with MRI. This provides the possibility and a noninvasive method to detect small, early stage hepatic metastases.

 

 

Keywords: 744 tumors • 552 imaging methods (CT, FA, ICG, MRI, OCT, RTA, SLO, ultrasound) • 452 choroid