Synthesis and in vivo evaluation of novel radiotracers for the in vivo imaging of the norepinephrine transporter

Wilson, Alan A.; Johnson, David; Mozley, David; Hussey, Doug; Ginovart, Nathalie; Nóbrega, José N.; García, Armando; Meyer, Jeffery H.; Houle, Sylvain

doi:10.1016/s0969-8051(02)00420-1

Cited by 83 publications

(74 citation statements)

References 25 publications

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“…The ratio of hypothalamus to striatum, representing the target to non-target ratio, was about 2.1 ( Table 2). This value is slightly higher than the ratio reported previously for [ 125 I]INXT 7 [8] and it is comparable to the ratio reported for 11 C-MeNER, 2, a reboxetine derivative [9]. Despite the lower in vitro binding affinity of [21].…”

Section: Biological Evaluationssupporting

confidence: 74%

“…(S,S)-[ 11 C]MeNER 2 showed the highest hypothalamus to striatum (target to non-target) ratio of 2.5 at 60 min post-iv injection in rats. In vitro autoradiography of rat brain slices indicated that its localization correlated well with the known distribution of NET [9]. Imaging studies in nonhuman primates using (S,S)-[ 11 C]MeNER 2 exhibited a reasonable midbrain to striatum ratio of 1.4-1.6 [10].…”

Section: Introductionmentioning

confidence: 64%

“…Up to this point, the most promising NET specific radiotracer has been a methyl derivative of reboxetine, (S,S)-[ 11 C]-(α-(2-methoxyphenoxy)benzyl)morpholine (MeNER) 2 ( Fig.1), which is a PET imaging agent [9][10][11]. (S,S)-[ 11 C]MeNER 2 showed the highest hypothalamus to striatum (target to non-target) ratio of 2.5 at 60 min post-iv injection in rats.…”

Section: Introductionmentioning

confidence: 99%

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(R)-N-Methyl-3-(3-125I-pyridin-2-yloxy)-3-phenylpropan-1-amine: a novel probe for norepinephrine transporters

Balagopal¹,

Kung²,

Lieberman³

et al. 2008

Nuclear Medicine and Biology

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Alterations in the serotonin and norepinephrine neuronal functions have been observed in patients with major depression. Several antidepressants bind to both serotonin transporters (SERT) and norepinephrine transporters (NET). The ability to image NET in the human brain would be a useful step toward understanding how alterations in NET relate to disease. In this study, we report the synthesis and characterization of a new series of derivatives of iodo-nisoxetine (INXT), a known radioiodinated probe. The most promising, (R)-N-methyl-3-(3-iodopyridin-2-yloxy)-3-phenylpropylamine (PYINXT) 9, displayed a high and saturable binding to NET with a K d value of 0.53 ± 0.03 nM. Biodistribution studies of [ 125 I]PYINXT in rats showed moderate initial brain uptake (0.54 %dose/organ at 2 min) with a relatively fast washout from the brain (0.16 %dose/organ at 2 hr) as compared to [ 125 I]INXT, 7. The hypothalamus (a NET rich region) to striatum (a region devoid of NET) ratio was found to be 2.14 at 4 hr post i.v. injection. The preliminary results suggest that this improved iodinated ligand, when labeled with 123 I, may be useful for mapping NET binding sites with SPECT in the living human brain.

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Section: Biological Evaluationssupporting

confidence: 74%

Section: Introductionmentioning

confidence: 64%

Section: Introductionmentioning

confidence: 99%

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(R)-N-Methyl-3-(3-125I-pyridin-2-yloxy)-3-phenylpropan-1-amine: a novel probe for norepinephrine transporters

Balagopal¹,

Kung²,

Lieberman³

et al. 2008

Nuclear Medicine and Biology

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“…Yield: 82%, yellow resin, (ppm) 2.3, 35.3, 57.0, 108.8, 108.9, 115.5, 115.9, 121.6, 122.0, 126.0, 127.7, 128.5, 129.1, 129.3, 129.4, 134.0, 134.1, 134.3 (23). Yield: 76%, yellow crystals, mp.…”

Section: General Procedures For the Synthesis Of 22-24mentioning

confidence: 99%

“…So far, radiolabeled NET binding reboxetine analogs [ ]methoxyphenoxy)benzyl)morpholine) have been described, which however display certain limitations such as metabolic instability, complex radiosyntheses, or late equilibria [22][23][24][25][26].…”

Section: Introductionmentioning

confidence: 99%

Synthesis and in Silico Evaluation of Novel Compounds for PET-Based Investigations of the Norepinephrine Transporter

et al. 2015

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Since the norepinephrine transporter (NET) is involved in a variety of diseases, the investigation of underlying dysregulation-mechanisms of the norepinephrine (NE) system is of major interest. Based on the previously described highly potent and selective NET ligand 1-(3-(methylamino)-1-phenylpropyl)-3-phenyl-1,3-dihydro-2H-benzimidaz-ol-2-one (Me@APPI), this paper aims at the development of several fluorinated methylaminebased analogs of this compound. The newly synthesized compounds were computationally

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Association of Posttraumatic Stress Disorder With Reduced In Vivo Norepinephrine Transporter Availability in the Locus Coeruleus

et al. 2013

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Synthesis and in vivo evaluation of novel radiotracers for the in vivo imaging of the norepinephrine transporter

Cited by 83 publications

References 25 publications

(R)-N-Methyl-3-(3-125I-pyridin-2-yloxy)-3-phenylpropan-1-amine: a novel probe for norepinephrine transporters

(R)-N-Methyl-3-(3-125I-pyridin-2-yloxy)-3-phenylpropan-1-amine: a novel probe for norepinephrine transporters

Synthesis and in Silico Evaluation of Novel Compounds for PET-Based Investigations of the Norepinephrine Transporter

Association of Posttraumatic Stress Disorder With Reduced In Vivo Norepinephrine Transporter Availability in the Locus Coeruleus

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