Journal of labelled compounds & radiopharmaceuticals最新文献_第8页

The inverse electron demand Diels–Alder cycloaddition with carbon-11 and fluorine-18: A gateway to pretargeted imaging across the blood–brain barrier 碳-11和氟-18的反电子需求Diels-Alder环加成:通过血脑屏障进行预靶向成像的门户

IF 1.8 4区医学

Journal of labelled compounds & radiopharmaceuticals Pub Date : 2023-05-05 DOI: 10.1002/jlcr.4029

Simon H. Zientek, Stephen Thompson, Selena Milicevic Sephton, Franklin I. Aigbirhio

{"title":"The inverse electron demand Diels–Alder cycloaddition with carbon-11 and fluorine-18: A gateway to pretargeted imaging across the blood–brain barrier","authors":"Simon H. Zientek, Stephen Thompson, Selena Milicevic Sephton, Franklin I. Aigbirhio","doi":"10.1002/jlcr.4029","DOIUrl":"10.1002/jlcr.4029","url":null,"abstract":"There is increased focus on developing tools to image large biomolecules, such as antibodies, within the brain using positron emission tomography (PET). The inverse electron demand Diels–Alder cycloaddition (IEDDA) reaction has offered the greatest prospect of achieving such a feat and has gained much interest over the past decade. The fast reaction kinetics of the IEDDA reaction opens up the possibility of utilising a pretargeted approach, whereby the subject is pretreated with a biomolecule that has high specificity for its target. A radiolabelled second component is then administered to the subject, enabling the biomolecule to be visualised by PET. However, for this to become common practice, there is a need for the development of either radiolabelled trans-cyclooctenes (TCOs) or tetrazines that can cross the blood–brain barrier (BBB). This review highlights the advancements in the development of both radiolabelled TCOs and tetrazines, which have been radiolabelled with either carbon-11 or fluorine-18 and show promise or have been evaluated for use in pretargeted PET imaging across the BBB.","PeriodicalId":16288,"journal":{"name":"Journal of labelled compounds & radiopharmaceuticals","volume":"66 9","pages":"249-268"},"PeriodicalIF":1.8,"publicationDate":"2023-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jlcr.4029","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9851509","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Automated radiosynthesis of 1-(2-[18F]fluoroethyl)-L-tryptophan ([18F]FETrp) for positron emission tomography (PET) imaging of cancer in humans 用于人类癌症正电子发射断层扫描（PET）成像的1-（2-[18F]氟乙基）-L-色氨酸（[18F]FETrp）的自动放射合成

IF 1.8 4区医学

Journal of labelled compounds & radiopharmaceuticals Pub Date : 2023-04-28 DOI: 10.1002/jlcr.4027

Huailei Jiang, Yan Guo, Hancheng Cai, Nerissa Viola, Anthony Frank Shields, Otto Muzik, Csaba Juhasz

{"title":"Automated radiosynthesis of 1-(2-[18F]fluoroethyl)-L-tryptophan ([18F]FETrp) for positron emission tomography (PET) imaging of cancer in humans","authors":"Huailei Jiang, Yan Guo, Hancheng Cai, Nerissa Viola, Anthony Frank Shields, Otto Muzik, Csaba Juhasz","doi":"10.1002/jlcr.4027","DOIUrl":"https://doi.org/10.1002/jlcr.4027","url":null,"abstract":"The radiotracer 1-(2-[18F]fluoroethyl)-L-tryptophan (L-[18F]FETrp or [18F]FETrp) is a substrate of indoleamine 2,3-dioxygenase, the initial and key enzyme of the kynurenine pathway associated with tumoral immune resistance. In preclinical positron emission tomography studies, [18F]FETrp is highly accumulated in a wide range of primary and metastatic cancers, such as lung cancer, prostate cancer, and gliomas. However, the clinical translation of this radiotracer into the first-in-human trial has not been reported, partially due to its racemization during radiofluorination which renders the purification of the final product challenging. However, efficient purification is essential for human studies in order to assure radiochemical and enantiomeric purity. In this work, we report a fully automated radiosynthesis of [18F]FETrp on a Synthra RNPlus research module, including a one-pot two steps radiosynthesis, dual independent chiral and reverse-phase semipreparative high-performance liquid chromatography purifications, and solid-phase extraction-assisted formulation. The presented approach has led to its Investigational New Drug application and approval that allows the testing of this tracer in humans.","PeriodicalId":16288,"journal":{"name":"Journal of labelled compounds & radiopharmaceuticals","volume":"66 7-8","pages":"180-188"},"PeriodicalIF":1.8,"publicationDate":"2023-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50146522","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1

Nitrilase mediated mild hydrolysis of a carbon-14 nitrile for the radiosynthesis of 4-(7-hydroxycarbamoyl-[1-14C-heptanoyl]-oxy)-benzoic acid methyl ester, [14C]-SHP-141: A novel class I/II histone deacetylase (HDAC) inhibitor 腈水解酶介导的碳-14腈温和水解用于放射合成4-（7-羟基氨基甲酰基-[1-14C-庚酰基]-氧基）-苯甲酸甲酯[14C]-SHP-141：一种新型I/II类组蛋白脱乙酰酶（HDAC）抑制剂

IF 1.8 4区医学

Journal of labelled compounds & radiopharmaceuticals Pub Date : 2023-04-25 DOI: 10.1002/jlcr.4026

Sean L. Kitson, William Watters, Thomas S. Moody, Todd Chappell, Ralph Mazitschek

{"title":"Nitrilase mediated mild hydrolysis of a carbon-14 nitrile for the radiosynthesis of 4-(7-hydroxycarbamoyl-[1-14C-heptanoyl]-oxy)-benzoic acid methyl ester, [14C]-SHP-141: A novel class I/II histone deacetylase (HDAC) inhibitor","authors":"Sean L. Kitson, William Watters, Thomas S. Moody, Todd Chappell, Ralph Mazitschek","doi":"10.1002/jlcr.4026","DOIUrl":"https://doi.org/10.1002/jlcr.4026","url":null,"abstract":"A strategy has been developed for the carbon-14 radiosynthesis of [14C]-SHP-141, a 4-(7-hydroxycarbamoyl-heptanoyloxy)-benzoic acid methyl ester derivative containing a terminal hydroxamic acid. The synthesis involved four radiochemical transformations. The key step in the radiosynthesis was the conversion of the 7-[14C]-cyano-heptanoic acid benzyloxyamide [14C]-4 directly into the carboxylic acid derivative, 7-benzyloxycarbamoyl-[14C]-heptanoic acid [14C]-8 using nitrilase-113 biocatalyst. The final step involved deprotection of the benzyloxy group using catalytic hydrogenation to facilitate the release of the hydroxamic acid without cleaving the phenoxy ester. [14C]-SHP-141 was isolated with a radiochemical purity of 90% and a specific activity of 190 μCi/mg from four radiochemical steps starting from potassium [14C]-cyanide in a radiochemical yield of 45%.","PeriodicalId":16288,"journal":{"name":"Journal of labelled compounds & radiopharmaceuticals","volume":"66 7-8","pages":"172-179"},"PeriodicalIF":1.8,"publicationDate":"2023-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50143125","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

RO6807936 as a novel positron emission tomography (PET) radiotracer for in vitro and in vivo visualization and quantification of beta-site amyloid precursor protein cleaving enzyme (BACE1) in the rodent and baboon brain RO6807936作为一种新型正电子发射断层扫描(PET)放射性示踪剂，用于啮齿动物和狒狒大脑中β -位点淀粉样蛋白前体切割酶(BACE1)的体外和体内可视化和定量

IF 1.8 4区医学

Journal of labelled compounds & radiopharmaceuticals Pub Date : 2023-04-24 DOI: 10.1002/jlcr.4025

Michael Honer, Alessandra Polara, Hiroto Kuwabara, Helmut Jacobsen, Axel Pähler, Thomas Hartung, Antonello Caruso, Daria Esterhazy, Markus Stoffel, Robert F. Dannals, Dean F. Wong, Edilio Borroni, Luca C. Gobbi

{"title":"RO6807936 as a novel positron emission tomography (PET) radiotracer for in vitro and in vivo visualization and quantification of beta-site amyloid precursor protein cleaving enzyme (BACE1) in the rodent and baboon brain","authors":"Michael Honer, Alessandra Polara, Hiroto Kuwabara, Helmut Jacobsen, Axel Pähler, Thomas Hartung, Antonello Caruso, Daria Esterhazy, Markus Stoffel, Robert F. Dannals, Dean F. Wong, Edilio Borroni, Luca C. Gobbi","doi":"10.1002/jlcr.4025","DOIUrl":"10.1002/jlcr.4025","url":null,"abstract":"The beta-site amyloid precursor protein cleaving enzyme (BACE1) is responsible for initiating the generation of beta-amyloid, the major constituent of amyloid plaques in Alzheimer's disease (AD). The purpose of this study was to develop a specific BACE1 radioligand for visualization of the distribution pattern and quantification of the BACE1 protein in the rodent and monkey brain both in vitro by autoradiography and in vivo by positron emission tomography (PET). The BACE1 inhibitor RO6807936 originating from an in-house chemical drug optimization program was selected based on its PET tracer-like physicochemical properties and a favorable pharmacokinetic profile. Saturation binding analysis of [3H]RO6807936 revealed specific and high-affinity binding (KD = 2.9 nM) and a low Bmax value (4.3 nM) of the BACE1 protein in native rat brain membranes. [3H]RO6807936 binding showed a ubiquitous distribution on rat brain slices in vitro with higher levels in the CA3 pyramidal cell layer and the granule cell layer of the hippocampus. In a next step, RO6807936 was successfully radiolabeled with carbon-11 and showed acceptable uptake in the baboon brain as well as a widespread and rather homogeneous distribution consistent with rodent data. In vivo blockade studies with a specific BACE1 inhibitor reduced uptake of the tracer to homogenous levels across brain regions and demonstrated specificity of the signal. Our data warrant further profiling of this PET tracer candidate in humans to investigate BACE1 expression in normal individuals and those with AD and as an imaging biomarker for target occupancy studies in clinical drug trials.","PeriodicalId":16288,"journal":{"name":"Journal of labelled compounds & radiopharmaceuticals","volume":"66 9","pages":"222-236"},"PeriodicalIF":1.8,"publicationDate":"2023-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9881807","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Synthesis of BI 894416 and BI 1342561, two potent and selective spleen tyrosine kinase inhibitors, labeled with carbon 14 and with deuterium BI 894416和BI 1342561的合成，两种有效的选择性脾酪氨酸激酶抑制剂，用碳14和氘标记

IF 1.8 4区医学

Journal of labelled compounds & radiopharmaceuticals Pub Date : 2023-04-14 DOI: 10.1002/jlcr.4024

Bachir Latli, Matt J. Hrapchak, Lalith P. Samankumara, Daniel R. Fandrick, Scott Pennino, Heewon Lee, Jinhua J. Song

{"title":"Synthesis of BI 894416 and BI 1342561, two potent and selective spleen tyrosine kinase inhibitors, labeled with carbon 14 and with deuterium","authors":"Bachir Latli, Matt J. Hrapchak, Lalith P. Samankumara, Daniel R. Fandrick, Scott Pennino, Heewon Lee, Jinhua J. Song","doi":"10.1002/jlcr.4024","DOIUrl":"10.1002/jlcr.4024","url":null,"abstract":"(R)-4-((R)-1-((6-(1-[tert-butyl]-1H-pyrazol-4-yl)-2-methyl-2H-pyrazolo[3,4-d]pyridin-4-yl)oxy)ethyl)pyrrolidin-2-one (BI 894416, 1) and (R)-4-((R)-1-((6-(1-[tert-butyl]-1H-pyrazol-4-yl)-2,3-dimethyl-2H-indazol-4-yl)oxy)ethyl)pyrrolidin-2-one (BI 1342561, 2) are two new potent and selective spleen tyrosine kinase inhibitors developed to treat severe asthma. Both compounds have similar structures and they differ only in the bicyclic moiety 2-methyl-2H-pyrazolo[4,3-c]pyridine in 1 versus 2,3-dimethyl-2H-indazole in 2. In the carbon 14 synthesis, 1-(1-[tert-butyl]-1H-pyrazol-4-yl)ethan-1-one-1-14C ([14C]-8) was prepared from the cyanation of 4-bromopyrazole using zinc [14C]cyanide followed by methyl lithium addition on the nitrile group. The enolate of [14C]-8 was then used to access these two bicyclic moieties via pyrano-pyrazoles [14C]-11 and [14C]-12, which were further transformed in few more steps to [14C]-(1) and [14C]-2. Both inhibitors contain a tert-butyl group. Introducing tert-butyl-d9 will not only provide internal standards for bioanalytical studies, but it is also expected to slow down the metabolism of these two compounds. Most of the metabolites of compound 1, for example, are the result of tert-butyl oxidation, like alcohol 3, acid 4, and the further N-demethylation of 4 to 5. The detailed preparation of these deuterium-labeled metabolites is also described.","PeriodicalId":16288,"journal":{"name":"Journal of labelled compounds & radiopharmaceuticals","volume":"66 4-6","pages":"155-168"},"PeriodicalIF":1.8,"publicationDate":"2023-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9672939","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Peptides for trans-blood–brain barrier delivery 用于跨血脑屏障递送的肽。

IF 1.8 4区医学

Journal of labelled compounds & radiopharmaceuticals Pub Date : 2023-04-01 DOI: 10.1002/jlcr.4023

Reuben Blades, Lars M. Ittner, Ole Tietz

引用次数: 1

Synthesis of beta-site amyloid precursor protein-cleaving enzyme 1 inhibitors BI 1147560 and BI 1181181 labeled with carbon-14 and deuterium 碳-14和氘标记β -位点淀粉样蛋白前体蛋白切割酶1抑制剂BI 1147560和BI 1181181的合成

IF 1.8 4区医学

Journal of labelled compounds & radiopharmaceuticals Pub Date : 2023-03-17 DOI: 10.1002/jlcr.4022

Bachir Latli, Matt J. Hrapchak, Jonathan T. Reeves, Heewon Lee, Jinhua J. Song

{"title":"Synthesis of beta-site amyloid precursor protein-cleaving enzyme 1 inhibitors BI 1147560 and BI 1181181 labeled with carbon-14 and deuterium","authors":"Bachir Latli, Matt J. Hrapchak, Jonathan T. Reeves, Heewon Lee, Jinhua J. Song","doi":"10.1002/jlcr.4022","DOIUrl":"10.1002/jlcr.4022","url":null,"abstract":"The generation of amyloid beta peptides that aggregate in the brain is believed to play a major role in Alzheimer's disease. In theory, the inhibition of beta-site amyloid precursor protein-cleaving enzyme 1 (BACE1), which catalyzes the initial rate-limiting step in amyloid beta production, may slow or stop Alzheimer's disease. Herein, we report the preparation of two potent BACE1 inhibitors, BI 1147560 (1) and BI 1181181 (2), labeled with carbon-14 and with deuterium. The use of advanced key chiral intermediates like 3 and 5 shortened the carbon-14 syntheses of these two compounds to five and six steps, respectively, and helped in preparing them with very high chemical purity and enantiomeric excess without deviating from the process chemistry route. For the deuterium synthesis, oxetan-3-ylmethanamine [2H6]-7 and 2-fluoro-2-methylpropan-1-amine [2H6]-9 were prepared then used with the chiral intermediate 5 to furnish deuterium labeled 1 and 2, respectively.","PeriodicalId":16288,"journal":{"name":"Journal of labelled compounds & radiopharmaceuticals","volume":"66 4-6","pages":"145-154"},"PeriodicalIF":1.8,"publicationDate":"2023-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9728795","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Strategies for designing novel positron emission tomography (PET) radiotracers to cross the blood–brain barrier 设计新型正电子发射断层扫描(PET)示踪剂以穿越血脑屏障的策略

IF 1.8 4区医学

Journal of labelled compounds & radiopharmaceuticals Pub Date : 2023-02-23 DOI: 10.1002/jlcr.4019

Anton Lindberg, Melissa Chassé, Cassis Varlow, Anna Pees, Neil Vasdev

引用次数: 4

A practical and environmentally friendly protocol for synthesis of α-deuterated carboxylic acids 一种实用且环保的合成α-氘化羧酸的方法

IF 1.8 4区医学

Journal of labelled compounds & radiopharmaceuticals Pub Date : 2023-02-23 DOI: 10.1002/jlcr.4021

Johan Wennerberg, Klaus Dreisch

引用次数: 0

Imidazolium-methylene-trifluoroborate: A novel radioprosthetic group validated with preclinical 18F-Positron Emission Tomography imaging of Prostate Specific Membrane Antigen in mice 咪唑亚甲基三氟硼酸盐：一种新的放射性假体组，通过小鼠前列腺特异性膜抗原的临床前18F正电子发射断层扫描成像进行验证

IF 1.8 4区医学

Journal of labelled compounds & radiopharmaceuticals Pub Date : 2023-02-22 DOI: 10.1002/jlcr.4020

Jerome Lozada, Hsiou-Ting Kuo, Wen Xuan Lin, Kuo-Shyan Lin, François Bénard, David M. Perrin

{"title":"Imidazolium-methylene-trifluoroborate: A novel radioprosthetic group validated with preclinical 18F-Positron Emission Tomography imaging of Prostate Specific Membrane Antigen in mice","authors":"Jerome Lozada, Hsiou-Ting Kuo, Wen Xuan Lin, Kuo-Shyan Lin, François Bénard, David M. Perrin","doi":"10.1002/jlcr.4020","DOIUrl":"https://doi.org/10.1002/jlcr.4020","url":null,"abstract":"Organotrifluoroborates have gained acceptance as radioprosthetic groups for radiofluorination. Of these, the zwitterionic prosthetic group “AMBF3” with a quaternary dimethylammonium ion dominates the trifluoroborate space. Herein, we report on imidazolium-methylene trifluoroborate (ImMBF3) as an alternative radioprosthetic group and report on its properties in the context of a PSMA-targeting EUK ligand that was previously been conjugated to AMBF3. The ImMBF3 is readily synthesized from imidazole and conjugated via CuAAC “click” chemistry to give a structure similar to PSMA-617. 18F-labeling proceeded in one step per our previous reports and imaged in LNCaP-xenograft bearing mice. The [18F]-PSMA-617-ImMBF3 tracer proved to be less polar (LogP7.4 = −2.95 ± 0.03) while showing a significantly lower solvolytic rate (t1/2 = 8100 min) and slightly higher molar activity (Am) at 174 ± 38 GBq/μmol. Tumor uptake was measured at 13.7 ± 4.8%ID/g and a tumor:muscle ratio of 74.2 ± 35.0, tumor:blood ratio of 21.4 ± 7.0, tumor:kidney ratio of 0.29 ± 0.14, and tumor:bone ratio of 23.5 ± 9.5. In comparison with previously reported PSMA-targeting EUK-AMBF3 conjugates, we have altered the LogP7.4 value, tuned the solvolytic half-life of the prosthetic, and increased radiochemical conversion while achieving similar tumor uptake, contrast ratios, and molar activities compared with AMBF3 bioconjugates.","PeriodicalId":16288,"journal":{"name":"Journal of labelled compounds & radiopharmaceuticals","volume":"66 4-6","pages":"130-137"},"PeriodicalIF":1.8,"publicationDate":"2023-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jlcr.4020","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50140757","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0