Effects of Focal Radiation on [18 F]-Fluoro-D-Glucose Positron Emission Tomography in the Brains of Miniature Pigs: Preliminary Findings on Local Metabolism.

OBJECTIVES: It would be a medically important advance if durable and focal neuromodulation of the brain could be delivered noninvasively and without ablation. This ongoing study seeks to elucidate the effects of precisely delivered ionizing radiation upon focal brain metabolism and the corresponding cellular integrity at that target. We hypothesize that focally delivered ionizing radiation to the brain can yield focal metabolic changes without lesioning the brain in the process. MATERIALS AND METHODS: We used stereotactic radiosurgery to deliver doses from 10 Gy to 120 Gy to the left primary motor cortex (M1) of Lee Sung miniature pigs (n = 8). One additional animal served as a nonirradiated control. We used positron emission tomography-computed tomography (PET-CT) to quantify radiation dose-dependent effects by calculating the ratio of standard uptake values (SUV) of 2-deoxy-2-[18 F]-fluoro-D-glucose (18 F-FDG) between the radiated (left) and irradiated (right) hemispheres across nine months. RESULTS: We found that the FDG-PET SUV ratio at the targeted M1 was significantly lowered from the pre-radiation baseline measurements for animals receiving 60 Gy or higher, with the effect persisting at nine months after radiosurgery. Only at 120 Gy was a lesion suggesting ablation visible at the M1 target. Animals treated at 60-100 Gy showed a reduced signal in the absence of an identifiable lesion, a result consistent with the occurrence of neuromodulation. CONCLUSION: Focal, noninvasive, and durable changes in brain activity can be induced without a magnetic resonance imaging (MRI)-visible lesion, a result that may be consistent with the occurrence of neuromodulation. This approach may provide new venues for the investigation of neuromodulatory treatments for disorders involving dysfunctional brain circuits. Postmortem pathological analysis is needed to elucidate whether there have been morphological changes not detected by MRI.

Impact of residual (18)F-fluoride in (18)F-FDOPA for the diagnosis of neuroblastoma.

OBJECTIVE: PET imaging with (18)F-FDOPA has been successfully applied in the diagnosis and surveillance of neuroblastoma (NB) by targeting the overexpression of aromatic L-amino acid decarboxylase. This study aims to assess the impact of residual (18)F-fluoride on (18)F-FDOPA PET in NB and to implement a method to maintain low (18)F-fluoride content in future studies. METHODS: Automatic synthesis of (18)F-FDOPA was based on the electrophilic method using TRACERlab FXFE module. Radio-TLC was employed to determine residual (18)F-fluoride levels. We analyzed the impact of residual (18)F-fluoride on the images of 35 patients undergoing (18)F-FDOPA PET at initial diagnosis and/or follow-ups of NB. RESULTS: In 35 batches of (18)F-FDOPA products from 9/28/2010 to 07/27/2011, the mean residual (18)F-fluoride level was 4.4 % (range 0.2-19.1 %). Residual (18)F-fluoride level ≥4.0 % was associated with dense uptake in the growth plates, skull, and pelvis on PET scans, which may interfere with the interpretation of (18)F-FDOPA imaging in NB. By applying stringent restraints in (18)F-FDOPA production, including regular renewal of reagents, exclusive use  of NH4OH, and timely replacement of HPLC column, the incidence of (18)F-FDOPA batches with residual (18)F-fluoride level ≥4.0 % was reduced from 33 to 4 % (P < 0.0001) during 7/30/2011-4/29/2013. CONCLUSION: By monitoring residual (18)F-fluoride levels and keeping stringent restraint procedures, low (18)F-fluoride content was achieved in most batches of (18)F-FDOPA, which diminished false-positive skeletal uptake. An appropriate upper limit of (18)F-fluoride level is suggested to be included in the criteria of routine quality control of (18)F-FDOPA productions.