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.