Synthesis, biological and autoradiographic evaluation of a novel Tc-99m radioligand derived from WAY 100635 with high affinity for the 5-HT1A receptor and the alpha1-adrenergic receptor

Heimbold, I.; Drews, A.; Kretzschmar, Marion; Varnäs, Katarina; Hall, Håkan; Halldin, Christer; Syhre, R.; Kraus, Werner; Pietzsch, Hans‐Jürgen; Seifert, Stefan; Brust, Peter; Johannsen, B.

doi:10.1016/s0969-8051(01)00313-4

Cited by 31 publications

(23 citation statements)

References 36 publications

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“…The successful development of 99m Tc‐TRODAT as a radioligand for the dopamine transporter has shown the feasibility of imaging specific transporters in the brain with radiotracers based on 99m Tc . Accordingly, many various radioligands have been made by several groups to develop 99m Tc complex for 5HT 1A receptor imaging, but there is no ideal 99m Tc agent for imaging central nervous system receptors . Over the last years, the radiochemistry of 99m Tc‐tricarbonyl complexes has been extended to find useful applications in radiochemistry and nuclear medicine.…”

Section: Introductionmentioning

confidence: 99%

2‐Amino‐3‐(1‐(4‐(4‐(2‐methoxyphenyl) piperazine‐1‐yl)butyl)‐1H‐1,2,3‐triazol‐4‐yl) propanoic acid: synthesized, ^99mTc‐tricarbonyl labeled, and bioevaluated as a potential 5HT_1A receptor ligand

Hassanzadeh

Erfani

Ebrahimi

2012

Labelled Comp Radiopharmac

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To develop a novel 5HT1A receptor imaging agent, a new methoxyphenyl piperazine derivative was synthesized and radiolabeled with 99mTc‐tricarbonyl precursor. We used the Cu (I)‐catalyzed cycloaddition of azide and terminal alkynes to synthesize 1, 2, 3 triazole as the metal chelating system. This synthesis provided reliable and reproducible method to attach technetium to the methoxyphenyl piperazine moiety. 99mTc‐tricabonyl labeling of ligand was performed at high radiochemical purity (greater than 95%). The radiolabeled compound was stable at least 24 h in room temperature. In vitro stability study in human serum albumin showed more than 90% stability in 37 °C incubation for 6 h. Biodistribution studies in rat have shown brain hippocampus uptake of 0.31 ± 0.02 %ID/g at 5‐min post‐injection. The favorable in vitro/in vivo stability, lipophilicity, and biodistribution profiles suggest that this radioconjugate is a good candidate for further exploration of its potential clinical application. Copyright © 2012 John Wiley & Sons, Ltd.

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Section: Introductionmentioning

confidence: 99%

2‐Amino‐3‐(1‐(4‐(4‐(2‐methoxyphenyl) piperazine‐1‐yl)butyl)‐1H‐1,2,3‐triazol‐4‐yl) propanoic acid: synthesized, ^99mTc‐tricarbonyl labeled, and bioevaluated as a potential 5HT_1A receptor ligand

Hassanzadeh

Erfani

Ebrahimi

2012

Labelled Comp Radiopharmac

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“…Many 99m Tc labeled complexes carrying MPP moiety with high affinity for the 5-HT 1A receptor have been reported [4][5][6][7][8]. Unfortunately, most of those agents confront with some problems such as low initial brain accumulation and high non-specific uptake.…”

Section: -Htmentioning

confidence: 99%

Synthesis of several MPP derivatives for 99mTc-labelling and evaluated as potential 5-HT1A receptor imaging agents

et al. 2011

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The (2-methoxyphenyl) piperazine (MPP) was selected as the functional group and conjugated to dithiocarbamate through different spacers. A series of new MPP derivatives (MPPnDTC, n = 2-6) were synthesized and radiolabelled with 99m Tc-nitrido core or 99m Tc-tricarboxyl core as potential 5-HT 1A receptor imaging agents. All the six 99m Tc-labelled complexes were lipophilic and neutral. Biodistribution results showed that those radiotracers had moderate initial brain and hippocampus uptake. There have no significant relation was observed between the biological properties of these tracers with the length of its carbon chain. The radioactivity concentrations of hippocampus of 99m TcN-MPP2DTC, 99m TcN-MPP3DTC, 99m TcN-MPP4DTC, 99m TcN-MPP5DTC, 99m TcN-MPP6DTC and 99m Tc(CO) 3 -MPP3DTC at 2 min post-injection time (p.i.) were 0.43, 1.15, 0.99, 1.04, 1.13 and 0.83 %ID/g, respectively.MPP, 99m Tc-nitrido core, 99m Tc-tricarboxyl core, 5-HT 1A receptor

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“…The successful development of 99m Tc-TRODAT as a radioligand for the dopamine transporter has shown the feasibility of imaging specific transporters in the brain with radiotracers based on 99m Tc [23,24] . Accordingly, many attempts have been made by several groups to develop 99m Tc complexes for 5-HT 1A receptor imaging [25][26][27][28][29][30] . Once again, fragments of WAY100635 was selected as prototype structure for developing 99m Tc labeled potential 5-HT 1A receptor imaging agent [27,28,31] .…”

Section: N-(2-(1-(4-(2-methoxyphenyl)piperazinyl)-ethyl))-n-(2-mentioning

confidence: 99%

“…Accordingly, many attempts have been made by several groups to develop 99m Tc complexes for 5-HT 1A receptor imaging [25][26][27][28][29][30] . Once again, fragments of WAY100635 was selected as prototype structure for developing 99m Tc labeled potential 5-HT 1A receptor imaging agent [27,28,31] . So far, there has no ideal 99m Tc agent for imaging CNS receptors [31] .…”

Section: N-(2-(1-(4-(2-methoxyphenyl)piperazinyl)-ethyl))-n-(2-mentioning

confidence: 99%

Synthesis and biological evaluation of 99mTc-HEDTA/HYNIC-MPP4 complex for 5-HT1A receptor imaging

Fan

Yan

Zhang

et al. 2009

Sci. China Ser. B-Chem.

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5-HT 1A receptor is associated with a variety of pathophysiology of neuropsychiatric disorders. Accordingly, we have synthesized a new 5-HT 1A receptor ligand (HYNIC-MPP4) and labeled it with 99m Tc using N-(2-hydroxyethyl)ethylenediaminetriacetic acid (HEDTA) as coligand. 99m Tc-HEDTA/HYNIC-MPP4 was prepared under pH 6 at room temperature. Biodistribution of 99m Tc-HEDTA/HYNIC-MPP4 in normal mice showed that this complex had moderate brain uptake (0.60% ID·g −1 at 2 min p.i.) and good retention. The hippocampus had the highest radioactivity uptake at 2 min p.i. (1.84% ID·g −1 ). The ratio of Hipp/CB was 3.1 at 2 min p.i. and increased to 4.4 at 60 min p.i. After blocking with 8-hydroxy-2-(dipropylamino) tetralin, the uptake of hippocampus was decreased significantly from 1.84% ID·g −1 to 0.53% ID·g −1 at 2 min p.i., while the cerebellum had no significant decrease. This 99m Tc complex could be a potent agent for 5-HT 1A receptor imaging. 5-HT1A receptor, 99m Tc, N-{4-[4-(2-methoxyphenyl)piperazin-1-yl]butyl}-3-(6-hydrazinyl) pyridyl carboxamide (HYNIC-MPP4), biodistribution

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Synthesis, biological and autoradiographic evaluation of a novel Tc-99m radioligand derived from WAY 100635 with high affinity for the 5-HT1A receptor and the alpha1-adrenergic receptor

Cited by 31 publications

References 36 publications

2‐Amino‐3‐(1‐(4‐(4‐(2‐methoxyphenyl) piperazine‐1‐yl)butyl)‐1H‐1,2,3‐triazol‐4‐yl) propanoic acid: synthesized, ^99mTc‐tricarbonyl labeled, and bioevaluated as a potential 5HT_1A receptor ligand

2‐Amino‐3‐(1‐(4‐(4‐(2‐methoxyphenyl) piperazine‐1‐yl)butyl)‐1H‐1,2,3‐triazol‐4‐yl) propanoic acid: synthesized, ^99mTc‐tricarbonyl labeled, and bioevaluated as a potential 5HT_1A receptor ligand

Synthesis of several MPP derivatives for 99mTc-labelling and evaluated as potential 5-HT1A receptor imaging agents

Synthesis and biological evaluation of 99mTc-HEDTA/HYNIC-MPP4 complex for 5-HT1A receptor imaging

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Synthesis, biological and autoradiographic evaluation of a novel Tc-99m radioligand derived from WAY 100635 with high affinity for the 5-HT1A receptor and the alpha1-adrenergic receptor

Cited by 31 publications

References 36 publications

2‐Amino‐3‐(1‐(4‐(4‐(2‐methoxyphenyl) piperazine‐1‐yl)butyl)‐1H‐1,2,3‐triazol‐4‐yl) propanoic acid: synthesized, 99mTc‐tricarbonyl labeled, and bioevaluated as a potential 5HT1A receptor ligand

2‐Amino‐3‐(1‐(4‐(4‐(2‐methoxyphenyl) piperazine‐1‐yl)butyl)‐1H‐1,2,3‐triazol‐4‐yl) propanoic acid: synthesized, 99mTc‐tricarbonyl labeled, and bioevaluated as a potential 5HT1A receptor ligand

Synthesis of several MPP derivatives for 99mTc-labelling and evaluated as potential 5-HT1A receptor imaging agents

Synthesis and biological evaluation of 99mTc-HEDTA/HYNIC-MPP4 complex for 5-HT1A receptor imaging

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Product

Resources

About

2‐Amino‐3‐(1‐(4‐(4‐(2‐methoxyphenyl) piperazine‐1‐yl)butyl)‐1H‐1,2,3‐triazol‐4‐yl) propanoic acid: synthesized, ^99mTc‐tricarbonyl labeled, and bioevaluated as a potential 5HT_1A receptor ligand

2‐Amino‐3‐(1‐(4‐(4‐(2‐methoxyphenyl) piperazine‐1‐yl)butyl)‐1H‐1,2,3‐triazol‐4‐yl) propanoic acid: synthesized, ^99mTc‐tricarbonyl labeled, and bioevaluated as a potential 5HT_1A receptor ligand