Evaluation of <sup>11</sup>C-Methionine PET and Anatomic MRI Associations in Diffuse Intrinsic Pontine Glioma.

Tinkle, Christopher L; Duncan, Elizabeth C; Doubrovin, Mikhail; Han, Yuanyuan; Li, Yimei; Kim, Hyun; Broniscer, Alberto; Snyder, Scott E et al. · J Nucl Med · 2019

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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 <sup>11</sup>C-methionine in pediatric patients with newly diagnosed DIPG and evaluated the associations of <sup>11</sup>C-methionine PET metrics with conventional MRI indices and survival outcomes. <b>Methods:</b> Twenty-two patients with newly diagnosed DIPG were prospectively enrolled on an institutional review board-approved investigational study of <sup>11</sup>C-methionine PET. All patients underwent baseline <sup>11</sup>C-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 <sup>11</sup>C-methionine uptake intensity and uniformity with survival, along with associations between <sup>11</sup>C-methionine uptake and conventional MRI tumor indices over time, were evaluated. <sup>11</sup>C-methionine PET voxel values within regions of interest were assessed as threshold values across proportions of the study population, and <sup>11</sup>C-methionine uptake at baseline was assessed relative to MRI-defined tumor progression. <b>Results:</b><sup>11</sup>C-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%). <sup>11</sup>C-methionine avidity within MRI-defined tumor was limited in extent, with 11 of 18 positive baseline <sup>11</sup>C-methionine PET scans (61%) showing less than 25% <sup>11</sup>C-methionine-avid tumor. The increase in total tumor volume with <sup>11</sup>C-methionine PET was relatively limited (17.2%; interquartile range, 6.53%-38.90%), as was the extent of <sup>11</sup>C-methionine uptake beyond the MRI-defined tumor (2.2%; interquartile range, 0.55%-10.88%). Although baseline <sup>11</sup>C-methionine PET intensity and uniformity metrics did not correlate with survival outcomes, initial <sup>11</sup>C-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 (<i>P</i>  =  0.07), yet <sup>11</sup>C-methionine PET indices at diagnosis did not differ significantly between atypical and typical DIPGs. <b>Conclusion:</b> Most newly diagnosed DIPGs are successfully visualized by <sup>11</sup>C-methionine PET. Baseline <sup>11</sup>C-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.

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