Anterior cingulate activation during Stroop task performance: a PET to MRI coregistration study of individual patients with schizophrenia

Objective: The authors used single-subject functional imaging analyses to 1) corroborate the findings of anterior cingulate hypoperfusion during an attentional task in schizophrenia and 2) examine whether anterior cingulate activation is associated with underlying morphology. Method: Five healthy subjects and six patients with schizophrenia underwent positron emission tomography scanning while they performed the Stroop task. The medial-frontal lobes were masked out for analysis, and activation peaks were individually coregistered to each subject's magnetic resonance imaging scan. Results: Healthy subjects showed activations in both limbic and paralimbic anterior cingulate regions. Patients with schizophrenia showed only paralimbic activations, and these were apparent only in patients having a paracingulate sulcus. Conclusions: These findings suggest that 1) patients with schizophrenia have limbic-anterior cingulate hypoperfusion during attentional tasks and 2) paralimbic activation is associated with underlying morphology

Toward Hypoxia-Selective Rhenium and Technetium Tricarbonyl Complexes

With the aim of preparing hypoxia-selective imaging and therapeutic agents, technetium­(I) and rhenium­(I) tricarbonyl complexes with pyridylhydrazone, dipyridylamine, and pyridylaminocarboxylate ligands containing nitrobenzyl or nitroimidazole functional groups have been prepared. The rhenium tricarbonyl complexes were synthesized with short reaction times using microwave irradiation. Rhenium tricarbonyl complexes with deprotonated <i>p</i>-nitrophenyl pyridylhydrazone ligands are luminescent, and this has been used to track their uptake in HeLa cells using confocal fluorescent microscopy. Selected rhenium tricarbonyl complexes displayed higher uptake in hypoxic cells when compared to normoxic cells. A ^99mTc tricarbonyl complex with a dipyridylamine ligand bearing a nitroimidazole functional group is stable in human serum and was shown to localize in a human renal cell carcinoma (RCC; SK-RC-52) tumor in a mouse

l-Tyrosine Confers Residualizing Properties to a d-Amino Acid-Rich Residualizing Peptide for Radioiodination of Internalizing Antibodies

Purpose: The aims of the study were to develop and evaluate a novel residualizing peptide for labeling internalizing antibodies with 124I to support clinical development using immuno-positron emission tomography (PET). Methods: The anti-epidermal growth factor receptor antibody ch806 was radiolabeled directly or indirectly with isotopes and various residualizing peptides. Azido-derivatized radiolabeled peptides were conjugated to dibenzylcyclooctyne-derivatized ch806 antibody via click chemistry. The radiochemical purities, antigen-expressing U87MG.de2-7 human glioblastoma cell-binding properties, and targeting of xenografts at 72 hours post injection of all radioconjugates were compared. Biodistribution of 124I-PEG4-tptddYddtpt-ch806 and immuno-PET imaging were evaluated in tumor-bearing mice. Results: Biodistribution studies using xenografts at 72 hours post injection showed that 131I-PEG4-tptddYddtpt-ch806 tumor uptake was similar to 111In-CHX-A″-DTPA-ch806. 125I-PEG4-tptddyddtpt-ch806 showed a lower tumor uptake value but higher than directly labeled 125I-ch806. 124I-PEG4-tptddYddtpt-ch806 was produced at 23% labeling efficiency, 98% radiochemical purity, 25.9 MBq/mg specific activity, and 64% cell binding in the presence of antigen excess. Tumor uptake for 124I-PEG4-tptddYddtpt-ch806 was similar to 111In-CHX-A″-DTPA-ch806. High-resolution immuno-PET/magnetic resonance imaging of tumors showed good correlation with biodistribution data. Conclusions: The mixed d/l-enantiomeric peptide, dThr-dPro-dThr-dAsp-dAsp-Tyr-dAsp-dAsp-dThr-dPro-dThr, is suitable for radiolabeling antibodies with radiohalogens such as 124I for high-resolution immuno-PET imaging of tumors and for evaluation in early-phase clinical trials