[11C]MET and [11C]PBR28 PET Imaging

Dosing and tolerability were previously established separately for the PET tracers [¹¹C]MET and [¹¹C]PBR28.^22,23 Imaging was performed using a high-resolution research tomograph (HRRT) PET scanner and combined with event-by-event head motion correction,²⁴ using MOLAR (Motion-compensation OSEM List-mode Algorithm for Resolution-recovery reconstruction) and the Vicra system (NDI, Waterloo, Canada).²⁵ For [¹¹C]MET studies, 517 ± 203 MBq of radiotracer was intravenously injected, and a 60-min dynamic scan was acquired. For [¹¹C]PBR28 studies, 670 ± 89 MBq of radiotracer was injected, and a 120-min dynamic scan was acquired. Frame duration was 6 × 30 sec, 3 × 1 min, 2 × 2 min, then 10 × 5 min for [¹¹C]MET and 22 × 5 min for [¹¹C]PBR28 scans. Arterial sampling was performed in 4/5 subjects to measure the input function used in kinetic modeling of PET data. The fifth patient was on long-term anticoagulation and could not safely undergo arterial sampling. Blood was assayed using a cross-calibrated gamma counter and by HPLC to measure the fraction of unmetabolized parent radiotracer.

Summed images (0–10 min post-injection) were created from the motion-corrected PET and registered to the subject’s MPRAGE image. Three regions of interest (ROIs) were defined on MRI and co-registered to the PET for tumor and normal brain: ROI over the lesion’s gadolinium enhancement, over normal/contralateral cortical tissue, and over normal cerebellum. ROI time-activity curves were generated, and kinetic analysis was applied. For [¹¹C]MET, the uptake rate constant K _i was estimated using Patlak analysis^26,27 when the blood input functions were available. For [¹¹C]PBR28, the volume of distribution V _T was estimated using multilinear analysis-1 (MA1)²⁸ when the blood input functions were available, and the distribution volume ratio (DVR) was estimated using the multilinear reference tissue method (MRTM),²⁹ with normal, contralateral cortical tissue as a reference region. In addition to regional kinetic parameters, parametric images of the kinetic parameters were obtained. SUV values were computed at 20-60 min post-injection for [¹¹C]MET and 40-60 min post-injection for [¹¹C]PBR28. In all cases, tumor-to-normal (benign/contralateral tissue) brain ratios of kinetic parameters (K _i ratio or distribution volume ratio: DVR) and SUV (SUVR: SUV ratio) were determined. Given the nature of the study, image analysis results were not blinded to the final diagnosis of TR or RN.