Automated radiosynthesis of [18F]PBR111 and [18F]PBR102 using the Tracerlab FXFN and Tracerlab MXFDG module for imaging the peripheral benzodiazepine receptor with PET

doi:10.1016/j.apradiso.2011.07.014

Applied Radiation and Isotopes

Volume 70, Issue 1, January 2012, Pages 176-183

https://doi.org/10.1016/j.apradiso.2011.07.014 Get rights and content

Abstract

[¹⁸F]PBR111 and [¹⁸F]PBR102 are selective radioligands for imaging of the Peripheral Benzodiazepine Receptor (PBR). We have developed a fully automated method for the radiosynthesis of [¹⁸F]PBR111 and [¹⁸F]PBR102 in the Tracerlab FX_FN (30±2% radiochemical yield non-decay-corrected for both tracers) and Tracerlab MX_FDG (25±2% radiochemical yield non-decay-corrected for both tracers) from the corresponding p-toluenesulfonyl precursors. For all tracers, radiochemical purity was >99% and specific activity was >150 GBq/μmol after less than 60 min of preparation time.

Highlights

► Radiosynthesis of novel ligands PBR111 and PBR102 with fluorine-18. ► Fully automated synthesis undertaken using the GE Tracerlab FX_FN and MX_FDG modules. ► Reproducible high yields suitable for clinical applications. ► Radiosynthesis and formulation achieved in less than 60 mins. ► PBR111 and PBR102 prepared in high radiochemical yield and specific activity.

Introduction

The Peripheral Benzodiazepine Receptor (PBR), also known as the translocator protein (18 kDa) or TSPO, is a trans-membrane multimeric protein complex primarily located in the outer mitochondrial membrane of cells. The PBR is predominantly expressed in the peripheral organs such as kidney, heart, adrenal, cortex, testis and ovaries and has low expression in the brain (Anholt et al., 1985). The increase in PBR density in a number of pathological conditions such as neurodegeneration (Benavides et al., 1987), inflammation (Vowinckel et al., 1997), Alzheimer′s (McGeer et al., 1988a, McGeer et al., 1988b, Diorio et al., 1991), Parkinson′s (McGeer et al., 1988b, Ouchi, 2005) and Huntington′s disease (Messmer and Reynolds, 1998) and multiple sclerosis (Vowinckel et al., 1997, Banati et al., 2000) suggest that the PBR could be a clinically useful marker for the detection of such disorders using positron emission tomography (PET). For this purpose, radiolabelled PBR ligands particulary [¹¹C]PK11195 (Benavides et al., 1983, Award and Gavish, 1987, Vowinckel et al., 1997) have been extensively used in PET imaging. However, the short half-life of carbon-11 (t_1/2=20 min) limits the wide-spread application of these tracers. Moreover, [¹¹C]PK11195 displays low brain uptake and extensive binding to plasma proteins, which complicates the quantitative analysis of the receptor density in this organ (Pappata et al., 1991, Pappata et al., 2000). This has prompted the development of [¹⁸F]labelled PBR ligands (t_1/2=110 min) such as a series of imidazo[1,2-a]pyridineacetamides including [¹⁸F]PBR111 ([¹⁸F]1) and [¹⁸F]PBR102 ([¹⁸F]2) (Katsifis et al., 2007, Fookes et al., 2008). The evaluation of [¹⁸F]PBR111 (2-(6-chloro-2-(4-(3-[¹⁸F]fluoropropoxy)phenyl)imidazo[1,2-a]pyridin-3-yl)-N,N-diethylacetamide) ([¹⁸F]1) and [¹⁸F]PBR102 (2-(6-chloro-2-(4-(2-[¹⁸F]fluoroethoxy)phenyl)imidazo[1,2-a]pyridin-3-yl)-N,N-diethylacetamide) ([¹⁸F]2) in rodents (Fookes et al., 2008) and primates (Eberl et al., 2009, Verschuer et al., 2009) have shown promising results for further investigation in the clinic and have suggested that these two radioligands have a good profile for brain imaging PBR expression in neurodegenerative disorders. Recently, the radiosynthesis of [¹⁸F]PBR111 ([¹⁸F]1) using a Zymate-XP robotic system has been reported (Dolle et al., 2008). However, this system is not a common PET production equipment in routine use and therefore reduces its usefulness for widespread evaluation and pre-clinical studies of [¹⁸F]PBR111 ([¹⁸F]1) and [¹⁸F]PBR102 ([¹⁸F]2).

In this work, we have developed a fully automated method for the radiosynthesis of [¹⁸F]PBR111 ([¹⁸F]1) and [¹⁸F]PBR102 ([¹⁸F]2) using the more common commercial synthesis modules, Tracerlab FX_FN and Tracerlab MX_FDG, from the corresponding p-toluenesulfonyl precursors.

Section snippets

Results and discussion

The synthesis of the two target compounds PBR111 (1) and PBR102 (2) and their corresponding p-toluenesulfonyl precursors 3 and 4, required for fluorine-18 labelling, have been described by Fookes et al., (2008) (Scheme 1). The radiolabelling of [¹⁸F]PBR111 ([¹⁸F]1) and [¹⁸F]PBR102 ([¹⁸F]2) on the Tracerlab FX_FN and Tracerlab MX_FDG synthesis module was achieved in one step synthesis by classical [¹⁸F]fluoride nucleophilic substitution of the p-toluenesulfonyl precursors 3 and 4 using potassium

General

Acetonitrile (DNA-quality) was purchased from Merck (Kilsyth, VIC, Australia). PBR111 (1) (2-(6-chloro-2-(4-(3-fluoropropoxy)phenyl)imidazo[1,2-a]pyridin-3-yl)-N,N-diethylacetamide), PBR102 (2) (2-(6-chloro-2-(4-(2-fluoroethoxy)phenyl)imidazo[1,2-a]pyridin-3-yl)-N,N-diethylacetamide) and the p-toluenesulfonyl precursors 3 (2-(6-chloro-2-(4-(3-tosyloxypropoxy)phenyl)imidazo[1,2-a]pyridin-3-yl)-N,N-diethylacetamide), 4 (2-(6-chloro-2-(4-(2-tosyloxyethoxy)phenyl)imidazo[1,2-a]pyridin-3-yl)-N,N

Conclusion

PBR111 (1) and PBR102 (2) have been labelled with [¹⁸F]fluorine using the Tracerlab FX_FN and Tracerlab MX_FDG synthesis module from the p-toluenesulfonyl precursors 3 and 4. This one step procedure is a convenient and reliable method to prepare [¹⁸F]PBR111 ([¹⁸F]1) or [¹⁸F]PBR102 ([¹⁸F]2) in an equivalent, reproducible, non-decay-corrected radiochemical yield of 30±2% (n=25 for [¹⁸F]1 and n=23 for [¹⁸F]2) in the Tracerlab FX_FN synthesis module and 25±2% (n=7 for [¹⁸F]1 and n=8 for [¹⁸F]2) in the

Acknowledgements

The authors wish to thank Ms. Cathy D. Jiang who contributed to the quality control analysis.

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Peripheral type benzodiazepine binding sites are a sensitive indirect index of neuronal damage
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Binding of [³H]Ro 5-4864 and [³H]PK11195 to cerebral cortex and peripheral tissues of various species: species differences and heterogeneity in peripheral benzodiazepine binding sites
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Quantitative comparison of the peripheral benzodiazepine receptor ligands [¹⁸F]PBR102 and [¹⁸F]PBR111 in baboons with PET
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A longitudinal MRI and TSPO PET-based investigation of brain region-specific neuroprotection by diazepam versus midazolam following organophosphate-induced seizures
2024, Neuropharmacology
Acute poisoning with organophosphorus cholinesterase inhibitors (OPs), such as OP nerve agents and pesticides, can cause life threatening cholinergic crisis and status epilepticus (SE). Survivors often experience significant morbidity, including brain injury, acquired epilepsy, and cognitive deficits. Current medical countermeasures for acute OP poisoning include a benzodiazepine to mitigate seizures. Diazepam was long the benzodiazepine included in autoinjectors used to treat OP-induced seizures, but it is now being replaced in many guidelines by midazolam, which terminates seizures more quickly, particularly when administered intramuscularly. While a direct correlation between seizure duration and the extent of brain injury has been widely reported, there are limited data comparing the neuroprotective efficacy of diazepam versus midazolam following acute OP intoxication. To address this data gap, we used non-invasive imaging techniques to longitudinally quantify neuropathology in a rat model of acute intoxication with the OP diisopropylfluorophosphate (DFP) with and without post-exposure intervention with diazepam or midazolam. Magnetic resonance imaging (MRI) was used to monitor neuropathology and brain atrophy, while positron emission tomography (PET) with a radiotracer targeting translocator protein (TSPO) was utilized to assess neuroinflammation. Animals were scanned at 3, 7, 28, 65, 91, and 168 days post-DFP and imaging metrics were quantitated for the hippocampus, amygdala, piriform cortex, thalamus, cerebral cortex and lateral ventricles. In the DFP-intoxicated rat, neuroinflammation persisted for the duration of the study coincident with progressive atrophy and ongoing tissue remodeling. Benzodiazepines attenuated neuropathology in a region-dependent manner, but neither benzodiazepine was effective in attenuating long-term neuroinflammation as detected by TSPO PET. Diffusion MRI and TSPO PET metrics were highly correlated with seizure severity, and early MRI and PET metrics were positively correlated with long-term brain atrophy. Collectively, these results suggest that anti-seizure therapy alone is insufficient to prevent long-lasting neuroinflammation and tissue remodeling.
Strain differences in the extent of brain injury in mice after tetramethylenedisulfotetramine-induced status epilepticus
2021, NeuroToxicology
Citation Excerpt :
PET imaging was performed using a radiolabeled ligand ([18F]PBR111) that targets TSPO 18 kDa, a validated marker of neuroinflammation (Ottoy et al., 2018; Van Camp et al., 2010). Automated synthesis of [18F]PBR111 was performed as previously described (Bourdier et al., 2012). PET scans were performed at the CMGI at the University of California, Davis, using a Siemens Inveon DPET small animal scanner (Siemens Corporation; Munich, Germany) or a microPET Focus 120 (Siemens Corporation), as previously described (Hobson et al., 2019).
Acute intoxication with tetramethylenedisulfotetramine (TETS) can trigger status epilepticus (SE) in humans. Survivors often exhibit long-term neurological effects, including electrographic abnormalities and cognitive deficits, but the pathogenic mechanisms linking the acute toxic effects of TETS to chronic outcomes are not known. Here, we use advanced in vivo imaging techniques to longitudinally monitor the neuropathological consequences of TETS-induced SE in two different mouse strains. Adult male NIH Swiss and C57BL/6J mice were injected with riluzole (10 mg/kg, i.p.), followed 10 min later by an acute dose of TETS (0.2 mg/kg in NIH Swiss; 0.3 mg/kg, i.p. in C57BL/6J) or an equal volume of vehicle (10% DMSO in 0.9% sterile saline). Different TETS doses were administered to trigger comparable seizure behavior between strains. Seizure behavior began within minutes of TETS exposure and rapidly progressed to SE that was terminated after 40 min by administration of midazolam (1.8 mg/kg, i.m.). The brains of vehicle and TETS-exposed mice were imaged using in vivo magnetic resonance (MR) and translocator protein (TSPO) positron emission tomography (PET) at 1, 3, 7, and 14 days post-exposure to monitor brain injury and neuroinflammation, respectively. When the brain scans of TETS mice were compared to those of vehicle controls, subtle and transient neuropathology was observed in both mouse strains, but more extensive and persistent TETS-induced neuropathology was observed in C57BL/6J mice. In addition, one NIH Swiss TETS mouse that did not respond to the midazolam therapy, but remained in SE for more than 2 h, displayed robust neuropathology as determined by in vivo imaging and confirmed by FluoroJade C staining and IBA-1 immunohistochemistry as readouts of neurodegeneration and neuroinflammation, respectively. These findings demonstrate that the extent of injury observed in the mouse brain after TETS-induced SE varied according to strain, dose of TETS and/or the duration of SE. These observations suggest that TETS-intoxicated humans who do not respond to antiseizure medication are at increased risk for brain injury.
TSPO PET upregulation predicts epileptic phenotype at disease onset independently from chronic TSPO expression in a rat model of temporal lobe epilepsy
2021, NeuroImage: Clinical
Neuroinflammation is a key component of epileptogenesis, the process leading to acquired epilepsy. In recent years, with the development of non-invasive in vivo positron emission tomography (PET) imaging of translocator protein 18 kDa (TSPO), a marker of neuroinflammation, it has become possible to perform longitudinal studies to characterize neuroinflammation at different disease stages in animal models of epileptogenesis. This study aimed to utilize the prognostic capability of TSPO PET imaging at disease onset (2 weeks post-SE) to categorize epileptic rats with distinct seizure burden based on TSPO levels at disease onset and investigate their association to TSPO expression at the chronic epilepsy stage. Controls (n = 14) and kainic acid-induced status epilepticus (KASE) rats (n = 41) were scanned non-invasively with [¹⁸F]PBR111 PET imaging measuring TSPO expression. Animals were monitored using video-electroencephalography (vEEG) up to chronic disease (12 weeks post-SE), at which TSPO levels ([³H]PK11195) as well as other post-mortem abnormalities (namely synaptic density ([³H]UCB-J), neuronal loss (NeuN), and neurodegeneration (FjC)) were investigated. By applying multivariate analysis, TSPO PET imaging at disease onset identified three KASE groups with significantly different spontaneous recurrent seizures (SRS) burden (defined as rare SRS, sporadic SRS, and frequent SRS) (p = 0.003). Interestingly, TSPO levels were significantly different when comparing the three KASE groups (p < 0.0001), with the frequent SRS group characterized only by a limited focal TSPO increase at disease onset. On the contrary, TSPO measured during chronic epilepsy was found to be the highest in the frequent SRS group and correlated with seizure burden (r = 0.826, p < 0.0001). Importantly, early and chronic TSPO levels did not correlate (r = −0.05). Finally, significant pathological changes in neuronal loss, synaptic density, and neurodegeneration were found not only when compared to control animals (p < 0.01), but also between the three KASE rat categories in the hippocampus (p < 0.05). Early and chronic TSPO upregulation following epileptogenic insult appear to be driven by two superimposed dynamic processes. The former is associated with epileptogenesis as measured at disease onset, while the latter is related to seizure frequency as quantified during chronic epilepsy.
Dose-on-demand production of diverse <sup>18</sup>F-radiotracers for preclinical applications using a continuous flow microfluidic system
2017, Nuclear Medicine and Biology
Citation Excerpt :
For example, Kuhnast et al. [23] reported the optimal [18F]PBR111 radiolabeling conditions included using a 6–7 mg/mL solution of the precursor 3 in DMSO and reacting it with [18F]fluoride for 5 min at 165 °C. In contrast, Bourdier et al. [24] used a 1 mg/mL solution of 3 in CH3CN and performed the radiolabeling for 5 min at 100 °C. Under microfluidic conditions, using a 2 mg/mL solution of the precursor 3 in CH3CN resulted in only 1% of [18F]PBR111 being produced at 90 °C using a total flow rate 40 μL/min.
The production of ¹⁸F-radiotracers using continuous flow microfluidics is under-utilized due to perceived equipment limitations. We describe the dose-on-demand principle, whereby the back-to-back production of multiple, diverse ¹⁸F-radiotracers can be prepared on the same day, on the same microfluidic system using the same batch of [¹⁸F]fluoride, the same microreactor, the same HPLC column and SPE cartridge to obtain a useful production yield.
[¹⁸F]MEL050, [¹⁸F]Fallypride and [¹⁸F]PBR111 were radiolabeled with [¹⁸F]fluoride using the Advion NanoTek Microfluidic Synthesis System. The outlet of the microreactor was connected to an automated HPLC injector and following the collection of the product, SPE reformulation produced the ¹⁸F-radiotracer in <10% ethanolic saline. A thorough automated cleaning procedure was implemented to ensure no cross-contamination between radiotracer synthesis.
The complete productions for [¹⁸F]MEL050 and [¹⁸F]Fallypride were performed at total flow rates of 20 μL/min, resulting in 40 ± 13% and 25 ± 13% RCY respectively. [¹⁸F]PBR111 was performed at 200 μL/min to obtain 27 ± 8% RCY. Molar activities for each ¹⁸F-radiotracer were >100 GBq/μmol and radiochemical purities were >97%, implying that the cleaning procedure was effective.
Using the same initial solution of [¹⁸F]fluoride, microreactor, HPLC column and SPE cartridge, three diverse ¹⁸F-radiotracers could be produced in yields sufficient for preclinical studies in a back-to-back fashion using a microfluidic system with no detectable cross-contamination.
Non-invasive PET imaging of brain inflammation at disease onset predicts spontaneous recurrent seizures and reflects comorbidities
2017, Brain, Behavior, and Immunity
Citation Excerpt :
The duration of SE, the latency to the first SRS, the duration of SRS, the circadian rhythm of SRS, the temporal evolution of SRS, and the total number of SRS (seizure burden) were determined. [18F]-PBR111 radiosynthesis was performed on a Fluorsynton I automated synthesis module (Comecer Netherlands, the Netherlands) according to Bourdier and colleagues (2012). PET scans were performed on an Inveon PET/Computed Tomography (CT) scanner (Siemens Preclinical Solution, USA).
Brain inflammation is an important factor in the conversion of a healthy brain into an epileptic one, a phenomenon known as epileptogenesis, offering a new entry point for prognostic tools. The development of anti-epileptogenic therapies to treat before or at disease onset is hampered by our inability to predict the severity of the disease outcome. In a rat model of temporal lobe epilepsy we aimed to assess whether in vivo non-invasive imaging of brain inflammation at disease onset was predictive of spontaneous recurrent seizures (SRS) frequency and severity of depression-like and sensorimotor-related comorbidities. To this end, translocator protein, a biomarker of inflammation, was imaged by means of positron emission tomography (PET) 2 and 4 weeks post-status epilepticus using [¹⁸F]-PBR111. Translocator protein was highly upregulated 2 weeks post-status epilepticus in limbic structures (up to 2.1-fold increase compared to controls in temporal lobe, P < 0.001), whereas 4 weeks post-status epilepticus, upregulation decreased (up to 1.6-fold increase compared to controls in temporal lobe, P < 0.01) and was only apparent in a subset of these regions. Animals were monitored with video-electroencephalography during all stages of disease (acute, latent – first seizures appearing around 2 weeks post-status epilepticus – and chronic phases), for a total of 12 weeks, in order to determine SRS frequency for each subject (range 0.00–0.83 SRS/day). We found that regional PET uptake at 2 and 4 weeks post-status epilepticus correlated with the severity of depression-like and sensorimotor-related comorbidities during chronic epilepsy (P < 0.05 for each test). Regional PET imaging did not correlate with SRS frequency, however, by applying a multivariate data-driven modeling approach based on translocator protein PET imaging at 2 weeks post-status epilepticus, we accurately predicted the frequency of SRS (R = 0.92; R² = 0.86; P < 0.0001) at the onset of epilepsy. This study not only demonstrates non-invasive imaging of translocator protein as a prognostic biomarker to ascertain SRS frequency, but also shows its capability to reflect the severity of depression-like and sensorimotor-related comorbidities. Our results are an encouraging step towards the development of anti-epileptogenic treatments by providing early quantitative assessment of SRS frequency and severity of comorbidities with high clinical relevance.
Synthesis and in vitro characterization of novel fluorinated derivatives of the translocator protein 18 kDa ligand CfO-DPA-714
2017, European Journal of Medicinal Chemistry
The translocator protein 18 kDa (TSPO) is today a validated target for a number of therapeutic applications, but also a well-recognized diagnostic/imaging biomarker for the evaluation of inflammatory related-disease state and progression, prompting the development of specific and dedicated TSPO ligands worldwide. For this purpose, pyrazolo[1,5-a]pyrimidine acetamides constitute a unique class of high affinity and selectivity TSPO ligands; it includes DPA-714, a fluorine-containing derivative that has also been labelled with the positron-emitter fluorine-18, and is nowadays widely used as a Positron Emission Tomography imaging probe. Recently, to prevent defluorination issues encountered in vivo with this tracer, a first series of analogues was reported where the oxygen atom bridging the phenyl ring of the core structure and the fluorinated moiety was replaced with a more robust linkage. Among this new series, CfO-DPA-714 was discovered as a highly promising TSPO ligand. Herein, a novel series of fluorinated analogues of the latter molecule were synthesized and in vitro characterized, where the pharmacomodulation at the amide position of the molecule was explored. Thirteen compounds were thus prepared from a common key-ester intermediate (synthesized in 7 steps from 4-iodobenzoate – 11% overall yield) and a set of commercially available amines and obtained with moderate to good yields (23–81%) and high purities (>95%). With one exception, all derivatives displayed nanomolar to subnanomolar affinity for the TSPO and also high selectivity versus the CBR (K_i (CBR)/K_i (TSPO) > 10³). Within this series, three compounds showed better K_i values (0.25, 0.26 and 0.30 nM) than that of DPA-714 (0.91 nM) and CfO-DPA-714 (0.37 nM), and favorable lipophilicity for brain penetration (3.6 < logD_7.4 < 4.4). Among these three compounds, the N-methyl-N-propyl amide analogue (9) exhibited similar metabolic stability when compared to CfO-DPA-714 in mouse, rat and human microsomes. Therefore, the latter compound stands out as a promising candidate for drug development or for use as a PET probe, once fluorine-18-labelled, for in vivo neuroinflammation imaging.

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Applied Radiation and Isotopes

Abstract

Highlights

Introduction

Section snippets

Results and discussion

General

Conclusion

Acknowledgements

References (18)

Peripheral type benzodiazepine binding sites are a sensitive indirect index of neuronal damage

Brain Res.

Peripheral benzodiazepine binding sites in Alzheimer′s disease frontal cortex and temporal cortex

Neurobiol. Aging

Peripheral-type benzodiazepine receptors: autoradiographic localization in whole-body sections of neonatal rats

J. Pharmacol. Exp. Ther.

Binding of [³H]Ro 5-4864 and [³H]PK11195 to cerebral cortex and peripheral tissues of various species: species differences and heterogeneity in peripheral benzodiazepine binding sites

J. Neurochem.

The peripheral benzodiazepine binding site in the brain in multiple sclerosis: quantitative in vivo imaging of microglia as a measure of disease activity

Brain

Labelling of peripheral-type benzodiazepine binding sites in the rat brain using PK11195, an isoquinoline carboxamide derivative: kinetic studies and autoradiographic localization

J. Neurochem.

Radiosyntheisis of [¹⁸F]PBR111, a selective radioligand for imaging the translocator protein (18 kDa) with PET

J. Labelled Compd. Radiopharm.

Quantitative comparison of the peripheral benzodiazepine receptor ligands [¹⁸F]PBR102 and [¹⁸F]PBR111 in baboons with PET

J. Nucl. Med.

Synthesis and biological evaluation os substituted [¹⁸F]imidazo[1,2-a]pyridines and [¹⁸F]Pyrazolo[1,5-a]pyrimidines for study of peripheral benzodiazepine receptor using positron emission tomography

J. Med. Chem.

Cited by (18)

A longitudinal MRI and TSPO PET-based investigation of brain region-specific neuroprotection by diazepam versus midazolam following organophosphate-induced seizures

Strain differences in the extent of brain injury in mice after tetramethylenedisulfotetramine-induced status epilepticus

TSPO PET upregulation predicts epileptic phenotype at disease onset independently from chronic TSPO expression in a rat model of temporal lobe epilepsy

Dose-on-demand production of diverse <sup>18</sup>F-radiotracers for preclinical applications using a continuous flow microfluidic system

Non-invasive PET imaging of brain inflammation at disease onset predicts spontaneous recurrent seizures and reflects comorbidities

Synthesis and in vitro characterization of novel fluorinated derivatives of the translocator protein 18 kDa ligand CfO-DPA-714

Automated radiosynthesis of [18F]PBR111 and [18F]PBR102 using the Tracerlab FXFN and Tracerlab MXFDG module for imaging the peripheral benzodiazepine receptor with PET

Abstract

Highlights

Introduction

Section snippets

Results and discussion

General

Conclusion

Acknowledgements

Brain Res.

Neurobiol. Aging

Peripheral-type benzodiazepine receptors: autoradiographic localization in whole-body sections of neonatal rats

J. Pharmacol. Exp. Ther.

Binding of [3H]Ro 5-4864 and [3H]PK11195 to cerebral cortex and peripheral tissues of various species: species differences and heterogeneity in peripheral benzodiazepine binding sites

J. Neurochem.

The peripheral benzodiazepine binding site in the brain in multiple sclerosis: quantitative in vivo imaging of microglia as a measure of disease activity

Brain

Labelling of peripheral-type benzodiazepine binding sites in the rat brain using PK11195, an isoquinoline carboxamide derivative: kinetic studies and autoradiographic localization

J. Neurochem.

Radiosyntheisis of [18F]PBR111, a selective radioligand for imaging the translocator protein (18 kDa) with PET

J. Labelled Compd. Radiopharm.

Quantitative comparison of the peripheral benzodiazepine receptor ligands [18F]PBR102 and [18F]PBR111 in baboons with PET

J. Nucl. Med.

Synthesis and biological evaluation os substituted [18F]imidazo[1,2-a]pyridines and [18F]Pyrazolo[1,5-a]pyrimidines for study of peripheral benzodiazepine receptor using positron emission tomography

J. Med. Chem.

Automated radiosynthesis of [¹⁸F]PBR111 and [¹⁸F]PBR102 using the Tracerlab FX_FN and Tracerlab MX_FDG module for imaging the peripheral benzodiazepine receptor with PET

Binding of [³H]Ro 5-4864 and [³H]PK11195 to cerebral cortex and peripheral tissues of various species: species differences and heterogeneity in peripheral benzodiazepine binding sites

Radiosyntheisis of [¹⁸F]PBR111, a selective radioligand for imaging the translocator protein (18 kDa) with PET

Quantitative comparison of the peripheral benzodiazepine receptor ligands [¹⁸F]PBR102 and [¹⁸F]PBR111 in baboons with PET

Synthesis and biological evaluation os substituted [¹⁸F]imidazo[1,2-a]pyridines and [¹⁸F]Pyrazolo[1,5-a]pyrimidines for study of peripheral benzodiazepine receptor using positron emission tomography