To determine the relationship between amyloid burden and neural function in healthy adults at risk for Alzheimer's Disease (AD), we used multimodal imaging with [C-11]Pittsburgh compound B positron emission tomography, [F-18]fluorodeoxyglucose, positron emission tomography, and magnetic resonance imaging, together with cognitive measurement in 201 subjects (mean age, 60.1 years; range, 46–73 years) from the Wisconsin Registry for Alzheimer's Prevention. Using a qualitative rating, 18% of the samples were strongly positive Beta-amyloid (Ab+), 41% indeterminate (Aβi), and 41% negative (Aβ–). Aβ+ was associated with older age, female sex, and showed trends for maternal family history of AD and APOE4. Relative to the Aβ– group, Aβ+ and Aβi participants had increased glucose metabolism in the bilateral thalamus; Aβ+ participants also had increased metabolism in the bilateral superior temporal gyrus. Aβ+ participants exhibited increased gray matter in the lateral parietal lobe bilaterally relative to the Aβ– group, and no areas of significant atrophy. Cognitive performance and self report cognitive and affective symptoms did not differ between groups. Amyloid burden can be identified in adults at a mean age of 60 years and is accompanied by glucometabolic increases in specific areas, but not atrophy or cognitive loss. This asymptomatic stage may be an opportune window for intervention to prevent progression to symptomatic AD.

Many solid tumors contain an overabundance of phospholipid ethers relative to normal cells. Capitalizing on this difference, we created cancer-targeted alkylphosphocholine (APC) analogs through structure-activity analyses. Depending on the iodine isotope used, radioiodinated APC analog CLR1404 was used as either a positron emission tomography (PET) imaging (124I) or molecular radiotherapeutic (131I) agent. CLR1404 analogs displayed prolonged tumor-selective retention in 55 in vivo rodent and human cancer and cancer stem cell models. 131I-CLR1404 also displayed efficacy (tumor growth suppression and survival extension) in a wide range of human tumor xenograft models. Human PET/CT (computed tomography) and SPECT (single-photon emission computed tomography)/CT imaging in advanced-cancer patients with 124I-CLR1404 or 131I-CLR1404, respectively, demonstrated selective uptake and prolonged retention in both primary and metastatic malignant tumors. Combined application of these chemically identical APC-based radioisosteres will enable personalized dual modality cancer therapy of using molecular 124I-CLR1404 tumor imaging for planning 131I-CLR1404 therapy.

Background Ictal-interictal continuum (IIC) continuous EEG (cEEG) patterns including periodic discharges and rhythmic delta activity are associated with poor outcome and in the appropriate clinical context, IIC patterns may represent “electroclinical” status epilepticus (SE). To clarify the significance of IIC patterns and their relationship to “electrographic” SE, we investigated FDG-PET imaging as a complementary metabolic biomarker of SE among patients with IIC patterns. Methods A single-center prospective clinical database was ascertained for patients undergoing FDG-PET during cEEG. Following MRI-PET co-registration, the maximum standardized uptake value in cortical and subcortical regions was compared to contralateral homologous and cerebellar regions. Consensus cEEG review and clinical rating of etiology and treatment response were performed retrospectively with blinding. Electrographic SE was classified as discrete seizures without interictal recovery or >3-Hz rhythmic IIC patterns. Electroclinical SE was classified as IIC patterns with electrographic and clinical response to anticonvulsants; clonic activity; or persistent post-ictal encephalopathy. Results Eighteen hospitalized subjects underwent FDG-PET during contemporaneous IIC patterns attributed to structural lesions (44 %), neuroinflammatory/neuroinfectious disease (39 %), or epilepsy (11 %). FDG-PET hypermetabolism was common (61 %) and predicted electrographic or electroclinical SE (sensitivity 79 % [95 % CI 53–93 %] and specificity 100 % [95 % CI 51–100 %]; p = 0.01). Excluding electrographic SE, hypermetabolism also predicted electroclinical SE (sensitivity 80 % [95 % CI 44–94 %] and specificity 100 % [95 % CI 51–100 %]; p = 0.01). Conclusions In hospitalized patients with IIC EEG patterns, FDG-PET hypermetabolism is common and is a candidate metabolic biomarker of electrographic SE or electroclinical SE.

This work describes the development and validation of a patient-specific Monte Carlo internal dosimetry platform called RAPID (Radiopharmaceutical Assessment Platform for Internal Dosimetry). RAPID utilizes serial PET/CT or SPECT/CT images to calculate voxelized three-dimensional (3D) internal dose distributions with the Monte Carlo code Geant4. RAPID's dosimetry calculations were benchmarked against previously published S-values and specific absorbed fractions (SAFs) calculated for monoenergetic photon and electron sources within the Zubal phantom and for S-values calculated for a variety of radionuclides within spherical tumor phantoms with sizes ranging from 1 to 1000 g. The majority of the S-values and SAFs calculated in the Zubal Phantom were within 5% of the previously published values with the exception of a few 10 keV photon SAFs that agreed within 10%, and one value within 16%. The S-values calculated in the spherical tumor phantoms agreed within 2% for Lu,I, I,F, and Cu, within 3.5% forAt and Bi, within 6.5% forSm, In,Zr, and Ra, and within 9% forY, Ga, andI. In conclusion, RAPID is capable of calculating accurate internal dosimetry at the voxel-level for a wide variety of radionuclides and could be a useful tool for calculating patient-specific 3D dose distributions.

Purpose: Highly constrained backprojection-local reconstruction (HYPR-LR) has made a dramatic impact on magnetic resonance angiography (MRA) and shows promise for positron emission tomography (PET) because of the improvements in the signal-to-noise ratio (SNR) it provides dynamic images. For PET in particular, HYPR-LR could improve kinetic analysis methods that are sensitive to noise. In this work, the authors closely examine the performance of HYPR-LR in the context of kinetic analysis, they develop an implementation of the algorithm that can be tailored to specific PET imaging tasks to minimize bias and maximize improvement in variance, and they provide a framework for validating the use of HYPR-LR processing for a particular imaging task. Methods: HYPR-LR can introduce errors into non sparse PET studies that might bias kinetic parameter estimates. An implementation of HYPR-LR is proposed that uses multiple temporally summed composite images that are formed based on the kinetics of the tracer being studied (HYPR-LR-MC). The effects of HYPR-LR-MC and of HYPR-LR using a full composite formed with all the frames in the study (HYPR-LR-FC) on the kinetic analysis of Pittsburgh compound-B ([11C]-PIB) are studied. HYPR-LR processing is compared to spatial smoothing. HYPR-LR processing was evaluated using both simulated and human studies. Nondisplaceable binding potential (BP ND ) parametric images were generated from fifty noise realizations of the same numerical phantom and eight [ 11 C]-PIB positive human scans before and after HYPR-LR processing or smoothing using the reference region Logan graphical method and receptor parametric mapping (RPM2). The bias and coefficient of variation in the frontal and parietal cortex in the simulated parametric images were calculated to evaluate the absolute performance of HYPR-LR processing. Bias in the human data was evaluated by comparing parametric image BP ND values averaged over large regions of interest (ROIs) to Logan estimates of the BP ND from TACs averaged over the same ROIs. Variance was assessed qualitatively in the parametric images and semiquantitatively by studying the correlation between voxel BP ND estimates from Logan analysis and RPM2. Results: Both the simulated and human data show that HYPR-LR-FC overestimates BP ND values in regions of high [ 11

Purpose (1) Determine the effect of 18Fluorodeoxyglucose Positron Emission Tomography (FDG-PET), magnetic resonance imaging (MRI), and electroencephalogram (EEG) on the decision for temporal lobe epilepsy (TLE) surgery. (2) Determine if FDG-PET, MRI, or EEG predict surgical outcome. Procedures All PET scans ordered (2000–2010) for epilepsy or seizure were tabulated. Medical records were investigated to determine eligibility and collect data. Statistical analysis included odds ratios, kappa statistics, univariate analysis, and logistic regression. Results 186 patients had an FDG-PET, 124 patients had TLE, 50 were surgical candidates, and 27 had operations with > 6 months follow-up. Median length of follow-up was 24 months. MRI, FDG-PET, and EEG were significant predictors of surgical candidacy (p<0.001) with odds ratio of 42.8, 20.4, and 6.3 respectively. PET was the only significant predictor of post-operative outcome. (p<0.01) Conclusion MRI had a trend toward most influence on surgical candidacy, but only FDG-PET predicted the surgical outcome.

ObjectiveTo investigate the correlation between characteristics of lateralized periodic discharges (LPDs) and glucose metabolism measured by 18F-fluorodeoxyglucose (FDG)–PET.MethodsWe retrospectively reviewed medical records to identify patients who underwent FDG-PET during EEG monitoring with LPDs present during the FDG uptake period. Two blinded board-certified neurophysiologists independently interpreted EEGs. FDG uptake was measured using standardized uptake value (SUV). Structural images were fused with PET images to aid with localization of SUV. Two PET readers independently measured maximum SUV. Relative SUV values were obtained by normalization of the maximum SUV to the SUV of pons (SUVRpons). LPD frequency was analyzed both as a categorical variable and as a continuous measure. Other secondary variables included duration, amplitude, presence of structural lesion, and “plus” EEG features such as rhythmic or fast sharp activity.ResultsNine patients were identified and 7 had a structural etiology for LPDs. Analysis using frequency as a categorical variable and continuous variable showed an association between increased LPD frequency and increased ipsilateral SUVRpons (p = 0.02). Metabolism associated with LPDs (0.5 Hz as a baseline) increased by a median of 100% at 1 Hz and for frequencies >1 Hz increased by a median of 309%. There were no statistically significant differences in SUVRpons for other factors including duration (p = 0.10), amplitude (p = 0.80), structural etiology (p = 0.55), or “plus” features such as rhythmic or fast sharp activity (p = 0.84).ConclusionsMetabolic activity increases monotonically with LPD frequency. LPD frequency should be a measure of interest when developing neuroprotection strategies in critical neurologic illness.

External-beam radiotherapy plays a critical role in the treatment of most pediatric solid tumors. Particularly in children, achieving an optimal therapeutic index to avoid damage to normal tissue is extremely important. Consequently, in metastatic disease, the utility of external-beam radiotherapy is limited. Molecular radiotherapy with tumor-targeted radionuclides may overcome some of these challenges, but to date there exists no single cancer-selective agent capable of treating various pediatric malignancies independently of their histopathologic origin. We tested the therapeutic potential of the clinical-grade alkyl-phospholipid ether analog CLR1404, 18-(-iodophenyl)octadecyl phosphocholine, as a scaffold for tumor-targeted radiotherapy of pediatric malignancies. Uptake of CLR1404 by pediatric solid tumor cells was tested in vitro by flow cytometry and in vivo by PET/CT imaging and dosimetry. The therapeutic potential ofI-CLR1404 was evaluated in xenograft models. In vitro, fluorescent CLR1404-BODIPY showed significant selective uptake in a variety of pediatric cancer lines compared with normal controls. In vivo tumor-targeted uptake in mouse xenograft models usingI-CLR1404 was confirmed by imaging. Single-dose intravenous injection of I-CLR1404 significantly delayed tumor growth in all rodent pediatric xenograft models and extended animal survival while demonstrating a favorable side effect profile.I-CLR1404 has the potential to become a tumor-targeted radiotherapeutic drug with broad applicability in pediatric oncology. Because I-CLR1404 has entered clinical trials in adults, our data warrant the development of pediatric clinical trials for this particularly vulnerable patient population.