Evaluation of 11C-Methionine PET and Anatomic MRI Associations in Diffuse Intrinsic Pontine Glioma

Abstract

The role of metabolic imaging in the diagnosis, treatment, and response assessment of diffuse intrinsic pontine glioma (DIPG) is poorly defined. We investigated the uptake of ¹¹C-methionine in pediatric patients with newly diagnosed DIPG and evaluated the associations of ¹¹C-methionine PET metrics with conventional MRI indices and survival outcomes. Methods: Twenty-two patients with newly diagnosed DIPG were prospectively enrolled on an institutional review board-approved investigational study of ¹¹C-methionine PET. All patients underwent baseline ¹¹C-methionine PET/CT, and initial treatment-response scans after chemotherapy or radiation therapy were obtained for 17 patients. Typical and atypical DIPGs were assessed clinically and radiographically and defined by multidisciplinary consensus. Three-dimensional regions of interest, reviewed by consensus between a nuclear medicine physician and a radiation oncologist, were delineated after coregistration of PET and MR images. Associations of ¹¹C-methionine uptake intensity and uniformity with survival, along with associations between ¹¹C-methionine uptake and conventional MRI tumor indices over time, were evaluated. ¹¹C-methionine PET voxel values within regions of interest were assessed as threshold values across proportions of the study population, and ¹¹C-methionine uptake at baseline was assessed relative to MRI-defined tumor progression. Results:¹¹C-methionine uptake above that of uninvolved brain tissue was observed in 18 of 22 baseline scans (82%) and 15 of 17 initial response scans (88%). ¹¹C-methionine avidity within MRI-defined tumor was limited in extent, with 11 of 18 positive baseline ¹¹C-methionine PET scans (61%) showing less than 25% ¹¹C-methionine-avid tumor. The increase in total tumor volume with ¹¹C-methionine PET was relatively limited (17.2%; interquartile range, 6.53%-38.90%), as was the extent of ¹¹C-methionine uptake beyond the MRI-defined tumor (2.2%; interquartile range, 0.55%-10.88%). Although baseline ¹¹C-methionine PET intensity and uniformity metrics did not correlate with survival outcomes, initial ¹¹C-methionine avidity overlapped with recurrent tumor in 100% of cases. A clinical diagnosis of atypical DIPG was associated with borderline significantly prolonged progression-free survival (P = 0.07), yet ¹¹C-methionine PET indices at diagnosis did not differ significantly between atypical and typical DIPGs. Conclusion: Most newly diagnosed DIPGs are successfully visualized by ¹¹C-methionine PET. Baseline ¹¹C-methionine uptake delineates regions at increased risk for recurrence, yet intensity and uniformity metrics did not correlate with treatment outcomes in children with DIPG in this study.

Keywords: 11C-methionine PET; DIPG; MRI; brainstem glioma; diffuse midline glioma; pediatric.

FIGURE 1.

PFS (A) and OS (B) estimates for total cohort, patients with typical DIPG, and patients with atypical DIPG, showing trend toward significant difference in PFS by DIPG type. CI = confidence interval.

FIGURE 2.

Box-and-whisker plots of imaging modality–defined tumor-volume change over time in patients with imaging abnormalities noted at both time points. Significant volume reductions were observed after RT for T2FLAIR MRI–defined tumor and for ¹¹C-methionine PET–defined tumor. Included are medians (connecting horizontal lines), means (diamonds), interquartile ranges (boxes), minimum and maximum values (whiskers), and outliers, that is, values beyond 1.5 interquartile ranges (circles).

FIGURE 3.

Example of concordant and discordant segmented tumor volumes based on T2FLAIR (magenta) and T1post (red) abnormalities on MR images and ¹¹C-methionine abnormality (yellow) on ¹¹C-methionine PET. (A) Concordance volumes with coregistered MRI- and ¹¹C-methionine PET–defined tumor (upper left) and indicated concordance volumes (blue = ¹¹C-methionine PET $\cap$ T2FLAIR; purple = ¹¹C-methionine PET $\cap$ T1post; green = T1post $\cap$ T2FLAIR). (B) Indicated discordance volumes (light green = ¹¹C-methionine PET − T2FLAIR; aqua = ¹¹C-methionine PET − T1post; dark blue = T1post − T2FLAIR) and concordant total tumor volume delineated on MRI and ¹¹C-methionine PET (red-orange, bottom right). *Physiologic uptake in exocrine glands.

FIGURE 4.

Waterfall plot of concordance and discordance of imaging modality–defined tumor volumes at diagnosis (A) and first surveillance (B) and contribution of ¹¹C-methionine PET volume to T2FLAIR-defined tumor volume at defined time points (C). Blue = typical DIPG; red = atypical DIPG; MET = methionine.

FIGURE 5.

Descriptive analysis of tumor volume–SUV proportions over indicated time points. Percentage of tumor volume in quartiles with SUV greater than or equal to specified SUV range is displayed with percentage of patients within each SUV range who had indicated volume–SUV relationships. Matrix subtraction of volume–SUV proportions between first surveillance and diagnosis are displayed on bottom row. Colorimetric scale (far right) uses progressively darker red values to indicate relative increase in percentage of patients’ specified volume–SUV metrics, whereas progressively darker green values indicate decrease.