Positron-emitting radioligands for studies in vivo-probes for human psychopharmacology

Pike, Victor W.

doi:10.1177/026988119300700202

Cited by 80 publications

(78 citation statements)

References 78 publications

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“…The LogD values for these radioligands were then determined experimentally and were in quite close agreement with those predicted by computation, again showing ligand 10 to have lower lipophilicity than 3, with a value lying in the range that is generally considered desirable for achieving good brain entry. 47,48 The formulated radioligands were radiochemically stable and also stable in monkey plasma for at least 30 min. In monkey blood, each radioligand was found to be distributed similarly and heavily into cells (Table 1), consistent with the known cellular presence of PBR.…”

Section: Discussionmentioning

confidence: 99%

Synthesis and Evaluation in Monkey of Two Sensitive ¹¹C-Labeled Aryloxyanilide Ligands for Imaging Brain Peripheral Benzodiazepine Receptors In Vivo

et al. 2007

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We sought to develop (11)C-labeled ligands for sensitive imaging of brain peripheral benzodiazepine receptors (PBR) in vivo. Two aryloxyanilides with high affinity for PBR were identified and synthesized, namely, N-acetyl- N-(2-methoxycarbonylbenzyl)-2-phenoxyaniline ( 3, PBR01) and N-(2-methoxybenzyl)- N-(4-phenoxypyridin-3-yl)acetamide ( 10, PBR28). 3 was hydrolyzed to 4, which was esterified with [ (11)C]iodomethane to provide [ (11)C] 3. The O-desmethyl analogue of 10 was converted into [ (11)C] 10 with [ (11)C]iodomethane. [ (11)C] 3 and [ (11)C] 10 were each injected into monkey to assess their brain kinetics with positron emission tomography (PET). After administration of either radioligand there was moderately high brain uptake of radioactivity. Receptor blocking and displacement experiments showed that a high proportion of this radioactivity was bound specifically to PBR. In monkey and rat, 3 and 10 were rapidly metabolized by ester hydrolysis and N-debenzylation, respectively, each to a single polar radiometabolite. [ (11)C] 3 and [ (11)C] 10 are effective for imaging PBR in monkey brain. [ (11)C] 10 especially warrants further evaluation in human subjects.

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Section: Discussionmentioning

confidence: 99%

Synthesis and Evaluation in Monkey of Two Sensitive ¹¹C-Labeled Aryloxyanilide Ligands for Imaging Brain Peripheral Benzodiazepine Receptors In Vivo

et al. 2007

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“…Although it is not easy to predict the extent of in vivo nonspecific binding, it is generally believed that the lipophilicity of an imaging agent is somewhat proportional to the degree of nonspecific binding (335). Therefore, lipophilicity is an important aspect to consider whilst designing an imaging agent.…”

Section: Molecular Imaging Agentsmentioning

confidence: 99%

A Molecular Imaging Primer: Modalities, Imaging Agents, and Applications

James

Gambhir

2012

Physiological Reviews

967

954

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Molecular imaging is revolutionizing the way we study the inner workings of the human body, diagnose diseases, approach drug design, and assess therapies. The field as a whole is making possible the visualization of complex biochemical processes involved in normal physiology and disease states, in real time, in living cells, tissues, and intact subjects. In this review, we focus specifically on molecular imaging of intact living subjects. We provide a basic primer for those who are new to molecular imaging, and a resource for those involved in the field. We begin by describing classical molecular imaging techniques together with their key strengths and limitations, after which we introduce some of the latest emerging imaging modalities. We provide an overview of the main classes of molecular imaging agents (i.e., small molecules, peptides, aptamers, engineered proteins, and nanoparticles) and cite examples of how molecular imaging is being applied in oncology, neuroscience, cardiology, gene therapy, cell tracking, and theranostics (therapy combined with diagnostics). A step-by-step guide to answering biological and/or clinical questions using the tools of molecular imaging is also provided. We conclude by discussing the grand challenges of the field, its future directions, and enormous potential for further impacting how we approach research and medicine.

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“…However, this lack of rationale for tracer selection was beginning to be addressed and some essential criteria were being established. 65 This of course still represents a major stumbling block in PET radiochemistry and efforts to overcome it by clarifying the physiochemical requirements for good tracers have continued. A computational approach was initiated at the MRC CU by setting up a database of PET radiotracers and associated physicochemical properties and attempts begun to correlate these with in vivo usefulness of the tracers concerned with a view to predicting efficacy based on physicochemical properties.…”

Section: -64mentioning

confidence: 99%

Building on a 50‐year legacy of the MRC Cyclotron Unit: the Hammersmith radiochemistry pioneering journey

Brady¹,

Clark²,

Luthra³

2007

Labelled Comp Radiopharmac

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The Medical Research Council Cyclotron Unit (MRC CU) situated at Hammersmith Hospital, London, is widely recognised for its pioneering developments in radiochemistry. The MRC CU became one of the largest and most comprehensive PET centres in the world. More recently, under the umbrella of a public/private partnership between the MRC and Amersham Health (now part of GE Healthcare) this centre has continued to advance PET research.This article reviews the 50-year history of radiochemistry development and application for medical research at Hammersmith.

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Positron-emitting radioligands for studies in vivo-probes for human psychopharmacology

Cited by 80 publications

References 78 publications

Synthesis and Evaluation in Monkey of Two Sensitive ¹¹C-Labeled Aryloxyanilide Ligands for Imaging Brain Peripheral Benzodiazepine Receptors In Vivo

Synthesis and Evaluation in Monkey of Two Sensitive ¹¹C-Labeled Aryloxyanilide Ligands for Imaging Brain Peripheral Benzodiazepine Receptors In Vivo

A Molecular Imaging Primer: Modalities, Imaging Agents, and Applications

Building on a 50‐year legacy of the MRC Cyclotron Unit: the Hammersmith radiochemistry pioneering journey

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Positron-emitting radioligands for studies in vivo-probes for human psychopharmacology

Cited by 80 publications

References 78 publications

Synthesis and Evaluation in Monkey of Two Sensitive 11C-Labeled Aryloxyanilide Ligands for Imaging Brain Peripheral Benzodiazepine Receptors In Vivo

Synthesis and Evaluation in Monkey of Two Sensitive 11C-Labeled Aryloxyanilide Ligands for Imaging Brain Peripheral Benzodiazepine Receptors In Vivo

A Molecular Imaging Primer: Modalities, Imaging Agents, and Applications

Building on a 50‐year legacy of the MRC Cyclotron Unit: the Hammersmith radiochemistry pioneering journey

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Synthesis and Evaluation in Monkey of Two Sensitive ¹¹C-Labeled Aryloxyanilide Ligands for Imaging Brain Peripheral Benzodiazepine Receptors In Vivo

Synthesis and Evaluation in Monkey of Two Sensitive ¹¹C-Labeled Aryloxyanilide Ligands for Imaging Brain Peripheral Benzodiazepine Receptors In Vivo