PET studies with biomarkers of regional neuronal activity (cerebral glucose metabolism or blood flow [CBF]) and amyloid-b (Ab) depositions provide complementary information for the early diagnosis of dementia and follow-up of patients with dementia. We investigated the validity of relative regional CBF estimates (R 1 ) gained from pharmacokinetic analyses of 11 Clabeled Pittsburgh compound B ( 11 C-PIB) PET studies as a marker of neuronal activity and neurodegeneration. Methods: Twenty-two patients with cognitive impairment (16 patients with early Alzheimer disease) underwent 18 F-FDG and 11 C-PIB PET studies for the assessment of regional glucose metabolism and Ab load. Parametric images of R 1 (relative CBF) and binding potential (BP ND ; Ab load) were generated by 2-step simplified reference tissue model (SRTM2) analyses of dynamic 11 C-PIB data. Volume-of-interest and voxel-based statistical analyses were performed to investigate the association between normalized 18 F-FDG uptake and 11 C-PIB R 1 and the correlation of these measures with symptom severity (Mini-Mental State Examination [MMSE] scores) in patients with Alzheimer disease. Results: SRTM2 analyses provided high-quality 11 C-PIB R 1 images that were comparable to 18 F-FDG PET images. Regional 11 C-PIB R 1 values strongly correlated with normalized regional 18 F-FDG uptake when correlations were calculated separately for each patient (R 2 [mean 6 SD], 0.73 6 0.11) or across all regions of all patients (R 2 , 0.62). A regression model including 18 F-FDG uptake, subject identification, and region grouping (into cortical, subcortical, and limbic regions to allow for possible differences in flow/metabolism coupling) accounted for 86% of total 11 C-PIB R 1 variability. Voxel-based correlation analyses of 18 F-FDG uptake and 11 C-PIB R 1 with MMSE scores revealed similar core findings of positive correlations in the posterior cingulate gyrus/precuneus and negative correlations (preserved activity) in the bilateral sensorimotor cortex. There was no correlation between Ab load (BP ND ) and MMSE scores. Conclusion: These results strongly suggest that 11 C-PIB R 1 can serve as a complementary biomarker of neuronal activity and, thus, neurodegeneration in addition to Ab load given by 11 C-PIB BP ND . Further studies are needed to validate the diagnostic value of dual-biomarker 11 C-PIB PET studies in comparison with combined 18 F-FDG and 11 C-PIB PET studies. Compared with the latter, dual-biomarker 11 C-PIB PET greatly reduces costs and burden for patients.
Nine patients with neuroblastoma stage IV were treated with the murine monoclonal antibody 14.G2a, directed against disialoganglioside GD2. The antibody was injected daily for 5-10 days and the total applied dosage ranged between 100 mg/m2 and 400 mg/m2. The peak serum levels of mAb 14.G2a ranged from 28 micrograms/ml to 61 micrograms/ml. Pharmacokinetic data obtained in three patients indicated that the serum elimination of mAb 14.G2a fits a two-compartment model, with an alpha-half-time (t1/2 alpha) between 0.66 h and 1.98 h and a beta-half-time (t1/2 beta) between 30.13 h and 53.33 h. All patients presented with a human anti-(mouse IgG) antibody response either during or shortly after therapy. Eight patients showed a continuous decrease in complement component C4 during therapy, as well as an initial decrease in C3c and an initial increase in C3a, all suggesting an activation of the complement cascade. Side-effects consisted of allergic reactions like pruritus, exanthema, urticaria and of severe pain, predominantly located in the abdomen and lower extremities, which required the use of continuous intravenous morphine. Four patients additionally developed a transient hypertension and one patient experienced a transient nephrotic syndrome. Three patients were treated in an adjuvant setting and are not evaluable for tumor response. Of the remaining six patients, two had a complete remission, two showed a partial remission, and two patients did not respond to treatment.
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