Browsing by Subject "radiosynthesis"

Now showing 1 - 10 of 14
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    Radiosynthesis of a carbon-11 labeled tetrahydrobenzisoxazole derivative as a new PET probe for γ-secretase imaging in Alzheimer's disease
    (Elsevier, 2020-01) Xu, Zhidong; Miao, Caihong; Dong, Fugui; Jia, Limeng; Li, Wei; Wang, Min; Liu, Wenqing; Zheng, Qi-Huang; Radiology and Imaging Sciences, School of Medicine
    To develop PET radiotracers for imaging of Alzheimer's disease, a new carbon-11 labeled potent and selective γ-secretase modulator (GSM) has been synthesized. The reference standard tetrahydrobenzisoxazole derivative 8 and its desmethylated precursor 9 were synthesized from cyclohex-2-en-1-one and 3-hydroxy-4-nitrobenzaldehyde in eight and nine steps with 11% and 5% overall chemical yield, respectively. The radiotracer [11C]8 was prepared from its corresponding precursor 9 with [11C]CH3OTf through O–11C-methylation and isolated by RP-HPLC combined with SPE in 45–50% radiochemical yield, based on [11C]CO2 and decay corrected to EOB. The radiochemical purity was >99%, and the molar activity (Am) at EOB was 555–740 GBq/μmol.
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    Radiosynthesis of a carbon-11-labeled AMPAR allosteric modulator as a new PET radioligand candidate for imaging of Alzheimer’s disease
    (Elsevier, 2019-05) Miao, Caihong; Dong, Fugui; Jia, Limeng; Li, Wei; Wang, Min; Zheng, Qi-Huang; Xu, Zhidong; Radiology and Imaging Sciences, School of Medicine
    To develop PET tracers for imaging of Alzheimer’s disease, a new carbon-11-labeled AMPAR allosteric modulator 4-cyclopropyl-7-(3-[11C]methoxyphenoxy)-3,4-dihydro-2H-benzo[e][1,2,4]thiadiazine 1,1-dioxide ([11C]8) has been synthesized. The reference standard 4-cyclopropyl-7-(3-methoxyphenoxy)-3,4-dihydro-2H-benzo[e][1,2,4]thiadiazine 1,1-dioxide (8) and its corresponding desmethylated precursor 4-cyclopropyl-7-(3-hydroxyphenoxy)-3,4-dihydro-2H-benzo[e][1,2,4]thiadiazine 1,1-dioxide (9) were synthesized from 4-methoxyabiline and chlorosulfonyl isocyanate in eight and nine steps with 3% and 1% overall chemical yield, respectively. The target tracer [11C]8 was prepared from the precursor 9 with [11C]CH3OTf through O-[11C]methylation and isolated by HPLC combined with SPE in 10–15% radiochemical yield, based on [11C]CO2 and decay corrected to end of bombardment (EOB). The radiochemical purity was >99%, and the molar activity (AM) at EOB was 370–740 GBq/μmol with a total synthesis time of 35–40-minutes from EOB.
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    Radiosynthesis of carbon-11 labeled PDE5 inhibitors as new potential PET radiotracers for imaging of Alzheimer's disease
    (Elsevier, 2019-12) Dong, Fugui; Du, Jie; Miao, Caihong; Jia, Limeng; Li, Wei; Wang, Min; Zheng, Qi-Huang; Xu, Zhidong; Radiology and Imaging Sciences, School of Medicine
    To develop PET tracers for imaging of Alzheimer's disease, new carbon-11 labeled potent and selective PDE5 inhibitors have been synthesized. The reference standards (5) and (12), and their corresponding desmethylated precursors (6) and (13) were synthesized from methyl 2-amino-5-bromobenzoate and (4-methoxyphenyl)methanamine in multiple steps with 2%, 1%, 1% and 0.2% overall chemical yield, respectively. The radiotracers ([11C]5) and ([11C]12) were prepared from their corresponding precursors 6 and 13 with [11C]CH3OTf through O–11C-methylation and isolated by HPLC combined with SPE in 40–50% radiochemical yield, based on [11C]CO2 and decay corrected to EOB. The radiochemical purity was >99%, and the molar activity (Am) at EOB was in a range of 370–740 GBq/μmol.
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    Synthesis and in vitro biological evaluation of new P2X7R radioligands [11C]halo-GSK1482160 analogs
    (Elsevier, 2019-06) Gao, Mingzhang; Wang, Min; Meyer, Jill A.; Territo, Paul R.; Hutchins, Gary D.; Zarrinmayeh, Hamideh; Zheng, Qi-Huang; Radiology and Imaging Sciences, School of Medicine
    The reference standards halo-GSK1482160 (F-, Br-, and I-) and their corresponding precursors desmethyl-halo-GSK1482160 (F-, Br-, and I-) were synthesized from (S)-1-methyl-5-oxopyrrolidine-2-carboxylic acid or (S)-5-oxopyrrolidine-2-carboxylic acid and 2-halo-3-(trifluoromethyl)benzylamine (F-, Br-, and I-) in one step with 45–93% yields. The target tracers [11C]halo-GSK1482160 (F-, Br-, and I-) were prepared from desmethyl-halo-GSK1482160 (F-, Br-, and I-) with [11C]CH3OTf under basic conditions (NaOH-Na2CO3, solid, w/w 1:2) through N-[11C]methylation and isolated by HPLC combined with SPE in 40–50% decay corrected radiochemical yield. The radiochemical purity was >99%, and the molar activity (AM) at end of bombardment (EOB) was 370–740 GBq/μmol. The potency of halo-GSK1482160 (F-, Br-, and I-) in comparison with GSK1482160 (Cl-) was determined by a radioligand competitive binding assay using [11C]GSK1482160, and the binding affinity Ki values for halo-GSK1482160 (F-, Br-, and I-) and GSK1482160 (Cl-) are 54.2, 2.5, 1.9 and 3.1 nM, respectively.
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    Synthesis and initial in vitro characterization of a new P2X7R radioligand [18F]IUR-1602
    (Elsevier, 2019-02) Gao, Mingzhang; Wang, Min; Glick-Wilson, Barbara E.; Meyer, Jill A.; Peters, Jonathan S.; Territo, Paul R.; Green, Mark A.; Hutchins, Gary D.; Zarrinmayeh, Hamideh; Zheng, Qi-Huang; Radiology and Imaging Sciences, School of Medicine
    The overexpression of P2X7R is associated with neuroinflammation and plays an important role in various neurodegenerative diseases. The [18F]fluoropropyl derivative of GSK1482160, [18F]IUR-1602, has been first prepared and examined as a new potential P2X7R radioligand. The reference standard IUR-1602 was synthesized from tert-butyl (S)-5-oxopyrrolidine-2-carboxylate, fluoropropylbromide, and 2-chloro-3-(trifluoromethyl)benzylamine with overall chemical yield 13% in three steps. The target tracer [18F]IUR-1602 was synthesized from desmethyl-GSK1482160 with 3-[18F]fluoropropyl tosylate, prepared from propane-1,3-diyl bis(4-methylbenzenesulfonate) and K[18F]F/Kryptofix2.2.2, in two steps and isolated by HPLC combined with SPE in 2–7% decay corrected radiochemical yield. The radiochemical purity was >99%, and the molar activity at end of bombardment (EOB) was 74–370 GBq/μmol. The potency of IUR-1602 in comparison with GSK1482160 was determined by a radioligand competitive binding assay using [11C]GSK1482160, and the binding affinity Ki values for IUR-1602 and GSK1482160 are 23.6 and 3.07 nM, respectively. The initial in vitro evaluation results, 8-fold less potency of [18F]IUR-1602 compared to [11C]GSK1482160, prevent further in vivo evaluation of [18F]IUR-1602 in animals and human.
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    Synthesis and preliminary biological evaluation of [11C]methyl (2-amino-5-(benzylthio)thiazolo[4,5-d]pyrimidin-7-yl)-d-leucinate for the fractalkine receptor (CX3CR1)
    (Elsevier, 2017-06) Gao, Mingzhang; Wang, Min; Meyer, Jill A.; Peters, Jonathan S.; Zarrinmayeh, Hamideh; Territo, Paul R.; Hutchins, Gary D.; Zheng, Qi-Huang; Radiology and Imaging Sciences, School of Medicine
    The reference standard methyl (2-amino-5-(benzylthio)thiazolo[4,5-d]pyrimidin-7-yl)-d-leucinate (5) and its precursor 2-amino-5-(benzylthio)thiazolo[4,5-d]pyrimidin-7-yl)-d-leucine (6) were synthesized from 6-amino-2-mercaptopyrimidin-4-ol and BnBr with overall chemical yield 7% in five steps and 4% in six steps, respectively. The target tracer [11C]methyl (2-amino-5-(benzylthio)thiazolo[4,5-d]pyrimidin-7-yl)-d-leucinate ([11C]5) was prepared from the acid precursor with [11C]CH3OTf through O-[11C]methylation and isolated by HPLC combined with SPE in 40–50% radiochemical yield, based on [11C]CO2 and decay corrected to end of bombardment (EOB). The radiochemical purity was >99%, and the specific activity (SA) at EOB was 370–1110 GBq/μmol with a total synthesis time of ∼40-min from EOB. The radioligand depletion experiment of [11C]5 did not display specific binding to CX3CR1, and the competitive binding assay of ligand 5 found much lower CX3CR1 binding affinity.
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    Synthesis and preliminary biological evaluation of radiolabeled 5-BDBD analogs as new candidate PET radioligands for P2X4 receptor
    (Elsevier, 2017-07) Wang, Min; Gao, Mingzhang; Meyer, Jill A.; Peters, Jonathan S.; Zarrinmayeh, Hamideh; Territo, Paul R.; Hutchins, Gary D.; Zheng, Qi-Huang; Department of Radiology and Imaging Sciences, IU School of Medicine
    P2X4 receptor has become an interesting molecular target for treatment and PET imaging of neuroinflammation and associated brain diseases such as Alzheimer’s disease. This study reports the first design, synthesis, radiolabeling and biological evaluation of new candidate PET P2X4 receptor radioligands using 5-BDBD, a specific P2X4 receptor antagonist, as a scaffold. 5-(3-Hydroxyphenyl)-1-[11C]methyl-1,3-dihydro-2H-benzofuro[3,2-e][1,4]diazepin-2-one (N-[11C]Me-5-BDBD analog, [11C]9) and 5-(3-Bromophenyl)-1-[11C]methyl-1,3-dihydro-2H-benzofuro[3,2-e][1,4]diazepin-2-one (N-[11C]Me-5-BDBD, [11C]8c) were prepared from their corresponding desmethylated precursors with [11C]CH3OTf through N-[11C]methylation and isolated by HPLC combined with SPE in 30–50% decay corrected radiochemical yields with 370–1110 GBq/µmol specific activity at EOB. 5-(3-[18F]Fluorophenyl)-1,3-dihydro-2H-benzofuro[3,2-e][1,4]diazepin-2-one ([18F]F-5-BDBD, [18F]5a) and 5-(3-(2-[18F]fluoroethoxy)phenyl)-1,3-dihydro-2H-benzofuro[3,2-e][1,4]diazepin-2-one ([18F]FE-5-BDBD, [18F]11) were prepared from their corresponding nitro- and tosylated precursors by nucleophilic substitution with K[18F]F/Kryptofix 2.2.2 and isolated by HPLC-SPE in 5–25% decay corrected radiochemical yields with 111–740 GBq/µmol specific activity at EOB. The preliminary biological evaluation of radiolabeled 5-BDBD analogs indicated these new radioligands have similar biological activity with their parent compound 5-BDBD.
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    Synthesis of [11C]GSK1482160 as a new PET agent for targeting P2X7 receptor
    (Elsevier, 2015-05) Gao, Mingzhang; Wang, Min; Green, Mark A.; Hutchins, Gary D.; Zheng, Qi-Huang; Department of Radiology and Imaging Sciences, School of Medicine
    The authentic standards GSK1482160 and its isomer, as well as the radiolabeling precursors desmethyl-GSK1482160 and Boc-protected desmethyl-GSK1482160 were synthesized from l-pyroglutamic acid, methyl l-pyroglutamate and 2-chloro-3-(trifluoromethyl)benzylamine with overall chemical yield 27–28% in 3 steps, 58% in 4 steps, 76% in 1 step and 33% in 2 steps, respectively. [11C]GSK1482160 was prepared from either desmethyl-GSK1482160 or Boc-protected desmethyl-GSK1482160 with [11C]CH3OTf through N-[11C]methylation and isolated by HPLC combined with SPE in 40–50% and 30–40% radiochemical yield, respectively, based on [11C]CO2 and decay corrected to end of bombardment (EOB). The radiochemical purity was >99%, and the specific activity at EOB was 370–1110 GBq/μmol with a total synthesis time of ∼40-min from EOB.
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    Synthesis of [11C]HG-10-102-01 as a new potential PET agent for imaging of LRRK2 enzyme in Parkinson’s disease
    (Elsevier, 2017-03) Wang, Min; Gao, Mingzhang; Xu, Zhidong; Zheng, Qi-Huang; Radiology and Imaging Sciences, School of Medicine
    The reference standard (4-((5-chloro-4-(methylamino)pyrimidin-2-yl)amino)-3-methoxyphenyl)(morpholino)methanone (HG-10-102-01) and its precursor (4-((5-chloro-4-(methylamino)pyrimidin-2-yl)amino)-3-hydroxyphenyl)(morpholino)methanone (desmethyl-HG-10-102-01) were synthesized from 2,4,5-trichloropyrimide and 3-methoxy-4-nitrobenzoic acid with overall chemical yield 49% in four steps and 14% in five steps, respectively. The target tracer (4-((5-chloro-4-(methylamino)pyrimidin-2-yl)amino)-3-[11C]methoxyphenyl)(morpholino)methanone ([11C]HG-10-102-01) was prepared from the precursor desmethyl-HG-10-102-01 with [11C]CH3OTf through O-[11C]methylation and isolated by HPLC combined with SPE in 45–55% radiochemical yield, based on [11C]CO2 and decay corrected to end of bombardment (EOB). The radiochemical purity was >99%, and the specific activity (SA) at EOB was 370–1110 GBq/μmol with a total synthesis time of ∼40-min from EOB.
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    Synthesis of a PET tau tracer [11C]PBB3 for imaging of Alzheimer’s disease
    (Elsevier, 2015-10) Wang, Min; Gao, Mingzhang; Xu, Zhidong; Zheng, Qi-Huang; Department of Radiology and Imaging, IU School of Medicine
    The authentic standard PBB3 and its precursor N-desmethyl-PBB3 as well as TBS-protected N-desmethyl-PBB3 precursor for radiolabeling were synthesized from 5-bromo-2-nitropyridine, acrolein diethyl acetal, 6-methoxy-2-methylbenzothiazole, and diethylchlorophosphate with overall chemical yield 1% in six steps, 2% in five steps, and 1% in six steps, respectively. [11C]PBB3 was prepared from either desmethyl-PBB3 or TBS-protected desmethyl-PBB3 with [11C]CH3OTf through N-[11C]methylation and isolated by HPLC combined with SPE in 20–25% and 15–20% radiochemical yield, respectively, based on [11C]CO2 and decay corrected to end of bombardment (EOB). The radiochemical purity was >99%, and the specific activity at EOB was 370–1110 GBq/μmol with a total synthesis time of ∼40-min from EOB.