Relatively Decreased 11C-Methionine Uptake within the Anaplastic Component of a Mixed-Grade Oligodendroglioma

SUMMARY: A 56-year-old woman presented with a mixed-grade oligodendroglioma. On 11C-methionine [MET]-positron-emission tomography images, heterogeneous uptake of MET was demonstrated in the mass lesion. The part of the lesion with higher MET uptake was identified as an ordinary oligodendroglioma, whereas the part of the lesion with lower MET uptake was an anaplastic component of oligodendroglioma. With oligodendrogliomas, we should be aware of the possibility that MET uptake decreases paradoxically with an increased anaplastic component of oligodendroglioma cells.


Case Report
A 56-year-old woman was admitted to our hospital with a 2-month history of headache. CT demonstrated a cystic right frontal mass with calcification. A 1.5T MR imaging system (Signa Horizon LX; GE Healthcare, Waukesha, Wis) was used to obtain transaxial T1weighted images. For contrast enhancement studies, 0.1 mmol/kg of body weight of gadolinium was injected intravenously. On MR imaging with gadolinium, an enhanced mass lesion with a large cyst was demonstrated in the right frontal lobe (Fig 1A). PET was carried out with an Advance NXi Imaging System (GE Medical Systems, Tokyo, Japan). After a 7-minute transmission scan was obtained, a dose of 370 MBq of MET was intravenously injected into a cubital vein within 1 minute. A 10-minute static PET scan was begun 20 minutes after MET injection. With MET-PET, high uptake of MET was demonstrated in the anterior right frontal lobe ( Fig 1B, tumor area A: short arrow), moderate uptake of MET was demonstrated in the anteromedial right frontal lobe (Fig 1B, tumor area B: long arrow), and high uptake of MET was demonstrated in the posteromedial right frontal lobe (Fig 1B, tumor area C: arrowhead). MET uptake ratio was defined as the ratio of radioisotope count of MET in tumor to that in normal gray matter. MET uptake ratio was 3.9 for tumor area A, 2.1 for tumor area B, and 4.1 for tumor area C.
PET and MR imaging datasets were transferred to a SUN workstation (SPARC MP20; Sun Microsystems, Mountain View, Calif). Coregistration of MET-PET and MR imaging data used a commercial software package (Dr. View; Asahi Kasei Joho System, Tokyo, Japan).
On coregistered images, tumor area B demonstrated intensive gadolinium enhancement; however, there was no enhancement in areas A or C (Fig 1C). Tumor area C corresponded largely with the calcified lesion seen on CT scans ( Fig 1D).
With reference to coregistered images, the tumor was totally removed with a neuronavigated surgical system (Brain LAB, Munich, Germany). Histologic examination was done with hematoxylin-eosin (H&E) staining. Within each tumor area, the degree of proliferative activity (Ki-67 index) was estimated. Tumor area A was a low-grade oligodendroglioma (Fig 2A). In tumor area B, histologic features consistent with high-grade (anaplastic) oligodendroglioma were evident ( Fig 2C). Tumor area C was a low-grade oligodendroglioma with abundant calcification (Fig 2E). The Ki-67 index was 1.8% for area A, 7.6% for area B, and 2.2% for area C (Fig 2B, D, F). Histologic and neuroradiologic features for all of the areas are shown in the Table.

Discussion
MET uptake by tumor tissue was first described in 1976 by Comar et al. 6 Previous reports have shown that MET uptake by gliomas depends on histologic grade. 1,3,7,8 Among glial tumors, oligodendrogliomas show high MET uptake. 9 It has been suggested that oligodendroglial tumors have a high rate of cell turnover, 10 which could enhance amino acid uptake and metabolism. High-grade oligodendrogliomas have been shown to have significantly higher MET uptake than lowgrade tumors. 9 However, no sophisticated correlation has been demonstrated between MET uptake and a histologic feature within an individual tumor that has combined low-and highgrade oligodendroglioma. In our patient, an exact local comparison of MET uptake and a histologic feature was performed using the neuronavigation system with reference to coregistered images. The oligodendroglioma in our case was separated in 3 tumor areas defined by different histologic features. We found a paradoxical result between MET uptake and histologic grade compared with previous studies. The lesion with higher MET uptake ratio (tumor areas A and C) had normal oligodendroglial cells, whereas the lesion with lower MET uptake ratio (tumor area B) was composed of anaplastic oligodendroglial cells. The in-  creased Ki-67 index of tumor area B was consistent with the malignant features seen with H&E staining.

Tumor
The reason for such a paradoxical result remains unclear, but we speculate that in a high-grade tumor, the cell is so deranged that its amino acid uptake mechanism no longer works and, hence, no MET uptake. On the other hand, anaplastic area was demonstrated with gadolinium-enhancement on MR imaging, which reflected disruption of the blood-brain barrier. We also suspect that MET uptake ratio does not always correlate with disruption of the blood-brain barrier. Only tumor area C demonstrated remarkable calcification independent of MET uptake ratio.

Conclusions
We demonstrated the case of relatively decreased MET uptake within the anaplastic component of a mixed-grade oligodendroglioma. Our exceptional case is interesting because of its value in elucidating the histologic and metabolic value of oligodendroglioma.