Abstract
Leptomeningeal carcinomatosis (LC) is the third most common metastatic complication of the central nervous system. However, the current modalities to reliably diagnose this condition are not satisfactory. Here, we report a preclinical proof of concept for a metabolomics-based diagnostic strategy using a rat LC model incorporating glioma cells that stably express green fluorescent protein. Cytologic diagnoses gave 66.7% sensitivity for the 7-day LC group and 0% for the 3-day LC group. MR imaging could not diagnose LC at these stages. In contrast, nuclear magnetic resonance-based metabolomics on cerebrospinal fluid detected marked differences between the normal and LC groups. Predictions based on the multivariate model provided sensitivity, specificity, and overall accuracy of 88% to 89% in both groups for LC diagnosis. Further statistical analyses identified lactate, acetate, and creatine as specific for the 7-day LC group, with glucose a specific marker of the normal group. Overall, we showed that the metabolomics approach provided both earlier and more accurate diagnostic results than cytology and MR imaging in current use.
Highlights
Leptomeningeal carcinomatosis (LC) is a disorder caused by the seeding of the leptomeninges, the pia, arachnoid, and cerebrospinal fluid (CSF) within the subarachnoid space, by malignant cells
All implanted rats (n 1⁄4 17) had F-98 cells infiltrating the leptomeninges as evidenced by GFP expression, which confirmed the proper establishment of LC in both 7-day (Fig. 3A) and 3-day (Fig. 3B) groups
Leptomeningeal infiltration of F-98 cells was more prominent in 7-day LC rats than in 3-day LC rats, suggesting that 3-day LC group is in an earlier phase of the LC development
Summary
Leptomeningeal carcinomatosis (LC) is a disorder caused by the seeding of the leptomeninges, the pia, arachnoid, and cerebrospinal fluid (CSF) within the subarachnoid space, by malignant cells. This disorder is the third most common metastatic complication of the central nervous system and increasingly common in cancer patients [1, 2]. Treatment can improve or stabilize a patient's neurological status and maintain their neurological quality of life [3]. An early diagnosis of LC is important to Authors' Affiliations: Departments of 1Radiology, and 2Radiation Applied Life Science, Seoul National University College of Medicine; 3College of Pharmacy, Natural Product Research Institute; 4College of Medicine, Seoul National University, Seoul; and 5Department of Biochemistry, Center for Advanced Medical Education by BK21 project, College of Medicine, Inha University, Incheon, Korea
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