Highly efficient synthesis of [
            <sup>11</sup>
            C]PE2I, a selective radioligand for the quantification of the dopamine transporter using PET

Dollé, Frédéric; Bottlaender, Michel; Demphel, Stéphane; Emond, Patrick; Fuseau, Chantal; Coulon, Christine; Ottaviani, M.; Valette, Héric; Loc’h, Christian; Halldin, Christer; Mauclaire, Laurent; Guilloteau, Denis; Mazièré, B.; Crouzel, C.

doi:10.1002/1099-1344(200009)43:10<997::aid-jlcr385>3.0.co;2-#

Cited by 35 publications

(16 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This transformation was used to register all dynamic frames of PET images. 8 The volume of interest (VOIs) of the Schiffer template corresponding to the striatum, thalamus, midbrain and cerebellum were used to generate regional timeactivity curves (TACs) on the co-registered images (27). For comparing the striatal For thalamus and cerebellum, the left and right sides were included in the same VOI.…”

Section: Image Analysissupporting

confidence: 65%

See 1 more Smart Citation

PET imaging of dopamine transporters with [ 18 F]FE-PE2I: Effects of anti-Parkinsonian drugs

Bang

Jung

Song

et al. 2016

Nuclear Medicine and Biology

View full text Add to dashboard Cite

show abstract

Section: Image Analysissupporting

confidence: 65%

“…Several animal models and human studies have been performed with 11 C labeled PE2I ( 11 C-PE2I) which showed favorable results (8,9). However, there are potential limitations of 11 C-PE2I in quantifying DAT.…”

mentioning

confidence: 99%

PET imaging of dopamine transporters with [ 18 F]FE-PE2I: Effects of anti-Parkinsonian drugs

Bang

Jung

Song

et al. 2016

Nuclear Medicine and Biology

View full text Add to dashboard Cite

show abstract

“…Rapid uptake in the striatum was observed with high contrast compared to cortical areas, and the striatal accumulation showed a plateau between 30 and 80 min post injection. These results were confirmed using [ 11 C]PE2I in Papio Anubis baboons (Dollé et al 2000). Rapid and high accumulation was found in the caudate nucleus and putamen, reaching a plateau 10 min post injection.…”

Section: In Vivo Evaluation In the Monkey In Physiological Conditionssupporting

confidence: 65%

“…[ 11 C]CO 2 is first trapped and reduced to [ 11 C]methanol by lithium aluminum hydride, followed by iodination in aqueous hydrogen iodide. This synthetic sequence provides [ 11 C]methyl triflate in 80% decay corrected yield 7 to 8 min after the end of the bombardment (Dollé et al 2000). Reaction of the acid precursor 3 (400-600 μg as the free base) with [ 11 C]methyl triflate in acetone containing NaOH in water yields 49-74% [ 11 C]PE2I after decay correction (Fig.…”

Section: Carbon Radiolabelingmentioning

confidence: 99%

PE2I: A Radiopharmaceutical for In vivo Exploration of the Dopamine Transporter

Emond

Guilloteau

Chalon

2008

CNS Neuroscience & Therapeutics

Self Cite

View full text Add to dashboard Cite

The membrane dopamine transporter (DAT) has a pivotal role in the regulation of dopamine (DA) neurotransmission involved in a number of physiological functions and brain disorders. Molecular imaging techniques, such as positron emission tomography (PET) and single photon emission computerized tomography (SPECT), are relevant tools to explore the DAT, and we developed the cocaine derivative N-(3-iodopro-2E-enyl)-2beta-carbomethoxy-3beta-(4'-methylphenyl) nortropane (PE2I) that has proved to be a very potent radiopharmaceutical to image the DAT by these techniques. Several methods are available to obtain PE2I labeled with iodine-123 or -125, carbon-11 and tritium. The pharmacological properties of PE2I have demonstrated that it has good affinity for the DAT (4 nM) and is one of the most selective DAT ligands. [(125)I]PE2I characterized postmortem in human brains has revealed very intense and selective binding in the basal ganglia. Ex vivo autoradiography in rats has shown that high level of [(125)I]PE2I accumulates in the striatum and also in the substantia nigra and ventral tegmental area. [(125)I]PE2I accumulation in the rat striatum is rapid, high, and selective, providing a maximum striatum/cerebellum ratio of 10 during the first 30 min post injection. Using SPECT or PET, rapid, high, and selective accumulation of PE2I was found in the caudate nucleus and putamen in monkeys, whereas rapid wash out from the cerebellum was observed. In vivo investigations in healthy humans have demonstrated that PE2I has high striatal uptake, low nonspecific binding, low radiation exposure, and a fairly short scanning time. A number of findings in various animal models of Parkinson's disease in rats and monkeys have demonstrated the high efficacy of PE2I for detection of reduction in the density of DAT, thus showing the potential value of PE2I for early diagnosis and evaluation of treatment of this disease. The excellent properties of PE2I are basis for the development of new DAT tracers for use in future PET explorations using fluor-18.

show abstract

“…The labeling of LBT-999 with tritium at its methyl ester function was performed as follows: 0.7 mg of nor-LBT-999 diluted in 300 l of N,N-dimethyl formamide was mixed with 150 l of [ 3 H]-methyliodide (370 MBq/ml, specific activity 3.1 TBq/mmol; Amersham, Uppsala, Sweden) and heated for 15 min at 90°C. After cooling to room temperature, 300 l of acetonitrile was added, and the [ 3 H]LBT-999 was purified by HPLC using a C 18 The labeling of LBT-999 with 11 C (t 1/2 : 20.4 min) at its methyl ester function was performed using standard conditions that have so far been used for the routine radiosynthesis of several radiotracers (Langer et al, 1999;Dollé et al, 2000Dollé et al, , 2002Sandell et al, 2000) and the efficient methylation reagent […”

Section: Preparation Of Nonlabeled Lbt-999 and [ 3 H/ 11 C]lbt-999mentioning

confidence: 99%

Pharmacological Characterization of (E)-N-(4-Fluorobut-2-enyl)-2β-carbomethoxy-3β-(4′-tolyl)nortropane (LBT-999) as a Highly Promising Fluorinated Ligand for the Dopamine Transporter

Chalon¹,

Hall²,

Saba³

et al. 2005

J Pharmacol Exp Ther

Self Cite

View full text Add to dashboard Cite

In the aim to develop an efficient fluorinated probe for positron emission tomography (PET) exploration of the dopamine transporter (DAT), we studied several in vitro and in vivo characteristics of the phenyltropane derivative (E)-N-(4-fluorobut-2-enyl)-2␤-carbomethoxy-3␤-(4Ј-tolyl)nortropane (LBT-999). In vitro on rat striatal membrane, [3 H]LBT-999 bound to a single site with a K d of 9 nM, B max of 17 pmol/mg protein, and a very high selectivity for the DAT [IC 50 for 1-{2-[bis-(4-fluorophenyl)-methoxy]ethyl}-4-(3-phenylpropyl)piperazine (GBR 12909) and (E)-N-(3-iodoprop-2-enyl)-2␤-carbomethoxy-3␤-(4Ј-methylphenyl)nortropane (PE2I): 2.4 and 18 nM, respectively; IC 50 for paroxetine, citalopram, N,N-dimethyl-2-(2-amino-4-methylphenyl thio)benzylamine, nisoxetine, and desipramine Ͼ1 M]. In vitro on post-mortem human brain sections, LBT-999 bound with high intensity to the caudate-putamen, weakly to the thalamus, and not in the neocortex and cerebellum. This binding was totally abolished in the presence of PE2I. Ex vivo cerebral biodistribution of [11 C]LBT-999 in rats showed striatum/ cerebellum radioactivity ratios of 18 and 25 at 30 and 60 min postinjection, respectively. This accumulation was strongly prevented by preinjection of GBR 12909, whereas paroxetine and nisoxetine had no effect. An in vivo kinetic PET study in three baboons showed a fast and very high uptake in the striatum, with a plateau at 30 min postinjection and a maximal putamen/ cerebellum ratio of 30. Taken together, these findings demonstrate that LBT-999 is a highly promising agent for in vivo exploration of the DAT. This probe is currently labeled with 18 F for further characterizations.As the membrane dopamine transporter (DAT) is very involved in a number of brain functions, in vivo exploration of this molecular target could become a relevant tool for the knowledge of pathophysiological mechanisms and diagnosis and follow-up of several neurological and psychiatric conditions. In this field, scintigraphic exploration of the DAT could be very useful for the early diagnosis and follow-up of Parkinson's disease. Most of these studies have been performed using single photon emission computerized tomography with radioligands chemically derived from the cocaine structure and labeled with 123 I such as 2␤-carbomethoxy-3␤-(4-iodophenyl)tropane (Innis et al., 1993;Seibyl et al., 1998; Article, publication date, and citation information can be found at http://jpet.aspetjournals.org. doi:10.1124/jpet.105.096792.ABBREVIATIONS: DAT, dopamine transporter; FPCIT,

show abstract

Highly efficient synthesis of [ ¹¹ C]PE2I, a selective radioligand for the quantification of the dopamine transporter using PET

Cited by 35 publications

References 0 publications

PET imaging of dopamine transporters with [ 18 F]FE-PE2I: Effects of anti-Parkinsonian drugs

PET imaging of dopamine transporters with [ 18 F]FE-PE2I: Effects of anti-Parkinsonian drugs

PE2I: A Radiopharmaceutical for In vivo Exploration of the Dopamine Transporter

Pharmacological Characterization of (E)-N-(4-Fluorobut-2-enyl)-2β-carbomethoxy-3β-(4′-tolyl)nortropane (LBT-999) as a Highly Promising Fluorinated Ligand for the Dopamine Transporter

Contact Info

Product

Resources

About

Highly efficient synthesis of [ 11 C]PE2I, a selective radioligand for the quantification of the dopamine transporter using PET

Cited by 35 publications

References 0 publications

PET imaging of dopamine transporters with [ 18 F]FE-PE2I: Effects of anti-Parkinsonian drugs

PET imaging of dopamine transporters with [ 18 F]FE-PE2I: Effects of anti-Parkinsonian drugs

PE2I: A Radiopharmaceutical for In vivo Exploration of the Dopamine Transporter

Pharmacological Characterization of (E)-N-(4-Fluorobut-2-enyl)-2β-carbomethoxy-3β-(4′-tolyl)nortropane (LBT-999) as a Highly Promising Fluorinated Ligand for the Dopamine Transporter

Contact Info

Product

Resources

About

Highly efficient synthesis of [ ¹¹ C]PE2I, a selective radioligand for the quantification of the dopamine transporter using PET