Three-step two-pot automated production of NCA [F]FDOPA with FlexLab module.

Automated three-step two-pot production of no-carrier-added (NCA) [F]FDOPA was first implemented in the iPHASE FlexLab module. Decay-corrected radiochemical yield (RCY) of [F]FDOPA synthesized by this method was 10~14% (n = 7) with a synthesis time of ~110 min [F]FDOPA was obtained in > 95% of radiochemical purity with a molar activity of ~431 GBq/μmol. With the method successfully implementing on the commercial FlexLab module and its built-in step-by-step activity monitoring, further processes optimization would be achieved.

Fluorine-18 radiolabeling of a nitrophenyl sulfoxide and its evaluation in an SK-RC-52 model of tumor hypoxia.

The significance of imaging hypoxia with the positron emission tomography ligand [(18) F]FMISO has been demonstrated in a variety of cancers. However, the slow kinetics of [(18) F]FMISO require a 2-h delay between tracer administration and patient scanning. Labeled chloroethyl sulfoxides have shown faster kinetics and higher contrast than [(18) F]FMISO in a rat model of ischemic stroke.

A versatile approach for the site-specific modification of recombinant antibodies using a combination of enzyme-mediated bioconjugation and click chemistry.

A unique two-step modular system for site-specific antibody modification and conjugation is reported. The first step of this approach uses enzymatic bioconjugation with the transpeptidase Sortase A for incorporation of strained cyclooctyne functional groups. The second step of this modular approach involves the azide-alkyne cycloaddition click reaction.

Single-chain antibody conjugated to a cage amine chelator and labeled with positron-emitting copper-64 for diagnostic imaging of activated platelets.

Imaging of activated platelets using an activation specific anti-GPIIb/IIIa integrin single-chain antibody (scFvanti-LIBS) conjugated to a positron emitting copper-64 complex of a cage amine sarcophagine chelator (MeCOSar) is reported. This tracer was compared in vitro to a (64)Cu(II) complex of the scFv conjugated to another commonly used macrocycle, DOTA. The scFvanti-LIBS-MeCOSar conjugate was radiolabeled with (64)Cu(II) rapidly under mild conditions and with higher specific activity than scFvanti-LIBS-DOTA.

Radiolabelling and evaluation of a novel sulfoxide as a PET imaging agent for tumor hypoxia.

[¹⁸F]FMISO is the most widely validated PET radiotracer for imaging hypoxic tissue. However, as a result of the pharmacokinetics of [¹⁸F]FMISO a 2h wait between tracer administration and patient scanning is required for optimal image acquisition. In order to develop hypoxia imaging agents with faster kinetics, we have synthesised and evaluated several F-18 labelled anilino sulfoxides.

Fully automated synthesis and coupling of [(18) F]FBEM to glutathione using the iPHASE FlexLab module.

Site-specific radiolabelling of peptides or antibodies using [(18) F]FBEM is often preferred over non-site-specific radiolabelling with [(18) F]SFB because it does not affect the affinity of the antibody to its target. Unfortunately, the synthesis of [(18) F]FBEM and its conjugation to thiol containing macromolecules requires some manual intervention, which leads to radiation exposure of the radiochemist. In this publication, we report on the complete automation of [(18) F]FBEM production and its subsequent conjugation to glutathione using a slightly modified iPHASE FlexLab module.

Rhenium and technetium tricarbonyl complexes of 1,4-Substituted pyridyl-1,2,3-triazole bidentate 'click' ligands conjugated to a targeting RGD peptide.

New 1,4-substituted pyridyl-1,2,3-triazole ligands with pendent phenyl isothiocyanate functional groups linked to the heterocycle through a short methylene or longer polyethylene glycol spacers were prepared and conjugated to a peptide containing the arginine-glycine-aspartic acid peptide motif. Rhenium and technetium carbonyl complexes, [M(CO)3 L(x) (py)](+) (where M = Re(I) or (99m) Tc(I) ; L(x)  = 1,4-substituted pyridyl-1,2,3-triazole ligands and py = pyridine) were prepared. One rhenium complex has been characterized by X-ray crystallography, and the luminescent properties of [M(CO)3 L(x) (py)](+) are reported.

Radiolabelling and evaluation of novel haloethylsulfoxides as PET imaging agents for tumor hypoxia.

The significance of imaging hypoxia with the PET ligand [(18)F]FMISO has been demonstrated in a variety of cancers. However, the slow kinetics of [(18)F]FMISO require a 2-h delay between tracer administration and patient scanning. Labelled chloroethyl sulfoxides have shown faster kinetics and higher contrast than [(18)F]FMISO in a rat model of ischemic stroke.

Dopamine D(1) receptor binding in the anterior cingulate cortex of patients with obsessive-compulsive disorder.

Functional neuroimaging studies in patients with obsessive-compulsive disorder (OCD) suggest there is a hyperactivation of the anterior cingulate cortex (ACC) during provocation of symptoms and conflict-inhibition tasks. Since dopamine, acting through D(1) receptors is suggested to modulate ACC activity, we hypothesised that there would be an altered D(1) binding potential (BP) in the ACC of OCD patients. Using [(11)C]-SCH23390 and positron emission tomography, we report significantly reduced D(1) BP in seven drug-free OCD patients compared with matched healthy controls.

Radiation dosimetry of beta-amyloid tracers 11C-PiB and 18F-BAY94-9172.

Unlabelled: Beta-amyloid (Abeta) imaging has great potential to aid in the diagnosis of Alzheimer disease and the development of therapeutics. The radiation dosimetry of Abeta radioligands may influence their application; therefore, we calculated and compared the effective doses (EDs) of 11C-PiB and a new 18F-labeled ligand, 18F-BAY94-9172.

Methods: Attenuation-corrected whole-body scans were performed at 0, 15, 30, 45, and 60 min after injection of 350+/-28 MBq (mean+/-SD) of 11C-PiB in 6 subjects and at 0, 20, 60, 120, and 180 min after injection of 319+/-27 MBq of 18F-BAY94-9172 in 3 subjects.

Dopamine D1 receptor binding in the striatum of patients with obsessive-compulsive disorder.

Background: Obsessive-compulsive disorder (OCD) is a chronic anxiety disorder of unknown aetiology. Psychopharmacological studies have suggested a role for the neurotransmitter serotonin however further evidence for serotonin in the aetiology of OCD is conflicted. The authors used positron emission tomography (PET) to examine the binding of the dopamine D(1) receptor antagonist [(11)C]-SCH23390 to D(1) receptors in the striatum of drug-free OCD patients compared with healthy controls.

Characterization of fluoromisonidazole binding in stroke.

Background And Purpose: [18F]fluoromisonidazole (FMISO) positron emission tomography has been used to image hypoxia early after human stroke. To further study the role of hypoxia in stroke and the binding characteristics of FMISO, we aimed to develop [3H]FMISO autoradiography in an animal stroke model. We hypothesized that [3H]FMISO binding is prolonged, allowing correlation with 24-hour histology, and that there is no FMISO binding after effective reperfusion.

Synthesis, 11C labeling and biological properties of derivatives of the tyrphostin AG957.

Four analogues of AG957, a known inhibitor of the tyrosine kinase p210(bcr-abl), have been synthesized and tested for their growth inhibitory effect against the BCR/ABL-positive FDrv210C cells as well as the epidermal growth factor (EGF) receptor-positive Baf/ERX cells. All compounds that can undergo oxidation to the corresponding quinone demonstrated inhibition of FDrv210C cells and Baf/ERX cells. Compounds that cannot become oxidized showed significantly less inhibition of BCR/ABL- or EGF receptor-mediated cell proliferation.

Imaging the ischemic penumbra with 18F-fluoromisonidazole in a rat model of ischemic stroke.

Background And Purpose: The ischemic penumbra is a major focus of stroke research. 18F-fluoromisonidazole (18F-FMISO), a positron emission tomography (PET) marker of hypoxic cells, has shown promise as a technique to image the penumbra in humans. Our aim was to delineate the pattern of 18F-FMISO binding in a rat middle cerebral artery transient thread-occlusion model, and correlate this with tissue outcome at 24 hours.

Cortical activation associated with the experience of auditory hallucinations and perception of human speech in schizophrenia: a PET correlation study.

A [H(2)(15)O] PET correlation analysis technique was employed to correlate brain activations associated with self-reports of auditory hallucinations in hallucinating patients (n=8) and perception of transient, random human speech in non-hallucinating (n=7) patients and normal control subjects (n=8). Perception of externally generated human speech amongst the non-hallucinating and normal control participants was associated with a consistent pattern of extensive bilateral auditory cortex activation (Brodmann areas 40/41/42/22). Hallucinating participants demonstrated a network of cortical activations including bilateral auditory cortex, left limbic regions, right medial frontal and right prefrontal regions.

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.

Imaging and quantitation of the hypoxic cell fraction of viable tumor in an animal model of intracerebral high grade glioma using [18F]fluoromisonidazole (FMISO).

We have demonstrated that FMISO uptake is significantly higher in tumor tissue in the C6 intracerebral glioma rat model compared to normal brain, and that there is persisting hypoxia in gliomas independent of tumor size. FMISO uptake was observed homogeneously throughout viable glioma tissue in tumor sizes ranging from 2mm to almost 1cm. Quantitation of uptake of FMISO showed a tumor/brain ratio of 1.