Abstract:
INTRODUCTION:The myeloperoxidase inhibitor AZD3241 has been selected as a candidate drug currently being developed to delay progression in patients with neurodegenerative brain disorders. Part of the decision tree for translation of AZD3241 into clinical studies included the need for assessment of brain exposure in non-human primates by PET microdosing. For that purpose a rapid multistep method for (11)C-labeling of AZD3241 was developed. METHODS:AZD3241 was labeled in the thio-carbonyl position starting from [(11)C]potassium cyanide in a 4-step procedure using microwave assisted heating. In the first step [(11)C]potassium cyanide was converted to [(11)C]potassium thiocyanate followed by reaction with benzoyl chloride to yield benzoyl [(11)C]isothiocyanate. The benzoyl [(11)C]isothiocyanate was subsequently reacted with the precursor ethyl 3-(2-isopropoxyethylamino)-1H-pyrrole-2-carboxylate and the formed intermediate underwent a base catalyzed cyclization to obtain [(11)C]AZD3241 in the final step. To assess [(11)C]AZD3241 brain exposure PET measurements were performed in three cynomolgus monkeys. RESULTS:[(11)C]AZD3241 was produced in good and reproducible radiochemical yield 710 ± 294 MBq (mean ± SD, n = 7). Total time of synthesis was 60 min from end of bombardment. The specific radioactivity was 9 ± 4GBq/μmol and the radiochemical purity was >98%. Following iv administration of [(11)C]AZD3241 there was a rapid presence of radioactivity in brain in each of the three monkeys. The distribution of [(11)C]AZD3241 to brain was fast and a Cmax of 1.9 to 2.6% of the injected radioactivity was observed within 1.5 min. [(11)C]AZD3241 was homogeneously distributed in brain. CONCLUSION:The MPO inhibitor AZD3241 was successfully labeled with carbon-11 in a challenging 4-step procedure in good radiochemical yield allowing PET microdosing studies in cynomolgus monkey. [(11)C]AZD3241 rapidly entered brain and confirmed adequate brain exposure to support translation of AZD3241 to phase 2a studies in patients.
journal_name
Nucl Med Bioljournal_title
Nuclear medicine and biologyauthors
Johnström P,Bergman L,Varnäs K,Malmquist J,Halldin C,Farde Ldoi
10.1016/j.nucmedbio.2015.02.001subject
Has Abstractpub_date
2015-06-01 00:00:00pages
555-60issue
6eissn
0969-8051issn
1872-9614pii
S0969-8051(15)00025-6journal_volume
42pub_type
杂志文章abstract::A column-switch high performance liquid chromatography method for the analysis of 4 mL of plasma is described with six examples of chromatography of [(11)C]-labeled positron-emission tomography imaging agents. Complete extraction of all but the most polar metabolites by the reverse phase capture column is achieved by ...
journal_title:Nuclear medicine and biology
pub_type: 杂志文章
doi:10.1016/s0969-8051(00)00125-6
更新日期:2000-08-01 00:00:00
abstract:INTRODUCTION:We synthesized and evaluated (64)Cu-labeled tetraiodothyroacetic acid (tetrac)-conjugated liposomes for PET imaging of tumor angiogenesis, because tetrac inhibits angiogenesis via integrin αVβ3. METHODS:Tetrac-PEG-DSPE and DOTA-PEG-DSPE were synthesized and formulated with other lipids into liposomes. The...
journal_title:Nuclear medicine and biology
pub_type: 杂志文章
doi:10.1016/j.nucmedbio.2013.08.003
更新日期:2013-11-01 00:00:00
abstract:INTRODUCTION:To determine the availability of nicotinic acetylcholine receptors in different human brain regions using the positron emission tomography (PET) radioligand 2-[18F]fluoro-A-85380 (2-[18F]FA) and invasive approaches for quantification, it is important to correct the arterial input function as well for plasm...
journal_title:Nuclear medicine and biology
pub_type: 杂志文章
doi:10.1016/j.nucmedbio.2006.07.012
更新日期:2006-10-01 00:00:00
abstract:INTRODUCTION:Dysregulation of the hepatocyte growth factor (HGF)/MET pathway has been implicated in various cancers. Rilotumumab is an investigational, fully human monoclonal antibody that binds and neutralizes HGF. The purpose of this study was to evaluate the efficacy of rilotumumab in a U-87 MG mouse xenograft tumor...
journal_title:Nuclear medicine and biology
pub_type: 杂志文章
doi:10.1016/j.nucmedbio.2013.01.004
更新日期:2013-05-01 00:00:00
abstract:INTRODUCTION:Current guidelines for brain PET imaging advice against the injection of diazepam prior to brain FDG-PET examination in order to avoid possible interactions of benzodiazepines with the radiotracer uptake. Nevertheless, many patients undergoing PET studies are likely to be under chronic treatment with benzo...
journal_title:Nuclear medicine and biology
pub_type: 杂志文章
doi:10.1016/j.nucmedbio.2016.09.001
更新日期:2016-12-01 00:00:00
abstract:INTRODUCTION:The heavy halogen (211)At is of great interest for targeted radiotherapy because it decays by the emission of short-range, high-energy α-particles. However, many astatine compounds that have been synthesized are unstable in vivo, providing motivation for seeking other (211)At labeling strategies. One relat...
journal_title:Nuclear medicine and biology
pub_type: 杂志文章
doi:10.1016/j.nucmedbio.2014.12.011
更新日期:2015-05-01 00:00:00
abstract::The diagnostic potential of PET using the amino acid analogue O-(2-[18F]fluoroethyl)-L-tyrosine ([18F]FET) in brain tumor diagnostics has been proven in many studies during the last two decades and is still the subject of multiple studies every year. In addition to standard magnetic resonance imaging (MRI), positron e...
journal_title:Nuclear medicine and biology
pub_type: 杂志文章,评审
doi:10.1016/j.nucmedbio.2020.02.006
更新日期:2020-02-19 00:00:00
abstract::We describe the synthesis of 2'-[(18)F]fluoroflumazenil (FFMZ), which differs from the typically used [(18)F]fluoroethylflumazenil (FEFMZ) for benzodiazepine receptor imaging. For one-pot one-step labeling, the precursors, 2'-tosyloxyflumazenil (TFMZ) and 2'-mesyloxyflumazenil (MFMZ), were synthesized in three steps. ...
journal_title:Nuclear medicine and biology
pub_type: 杂志文章
doi:10.1016/s0969-8051(03)00030-1
更新日期:2003-07-01 00:00:00
abstract::The premise that, over the course of Alzheimer's disease (AD), changes in the levels of the vesicular acetylcholine transporter (VAChT) occur in parallel with changes to other cholinergic marker proteins provides the basis for the applicability of benzovesamicol derivatives as radioligands for AD studies by single pho...
journal_title:Nuclear medicine and biology
pub_type: 杂志文章
doi:10.1016/j.nucmedbio.2007.07.011
更新日期:2007-11-01 00:00:00
abstract:INTRODUCTION:Altered lipid metabolism and subsequent changes in cellular lipid composition have been observed in prostate cancer cells, are associated with poor clinical outcome, and are promising targets for metabolic therapies. This study reports for the first time on the synthesis of a phospholipid radiotracer based...
journal_title:Nuclear medicine and biology
pub_type: 杂志文章
doi:10.1016/j.nucmedbio.2020.11.007
更新日期:2020-11-28 00:00:00
abstract::An ultrafast and efficient high-performance liquid chromatographic (LC) method was developed to purify positron emission tomography (PET) radiopharmaceuticals as well as for metabolite analysis of the plasma sample. Chromatographic separation was achieved on a short (60 mm length) semipreparative (10 mm I.D.) column p...
journal_title:Nuclear medicine and biology
pub_type: 杂志文章
doi:10.1016/j.nucmedbio.2009.08.002
更新日期:2010-01-01 00:00:00
abstract::Monoclonal antibodies (mAbs) such as the tumor-specific anti-epidermal growth factor receptor variant III (EGFRvIII) that are internalized and degraded after cell binding necessitate the use of radioiodination methods that minimize the loss of radioactivity from the tumor cell after intracellular processing. The purpo...
journal_title:Nuclear medicine and biology
pub_type: 杂志文章
doi:10.1016/s0969-8051(01)00277-3
更新日期:2002-01-01 00:00:00
abstract:INTRODUCTION:The selective 5-hydroxytryptamine type 2a receptor (5-HT(2A)R) radiotracer [(18)F]altanserin is a promising ligand for in vivo brain imaging in rodents. However, [(18)F]altanserin is a substrate of P-glycoprotein (P-gp) in rats. Its applicability might therefore be constrained by both a differential expres...
journal_title:Nuclear medicine and biology
pub_type: 杂志文章
doi:10.1016/j.nucmedbio.2013.09.001
更新日期:2014-01-01 00:00:00
abstract::We performed preclinical and clinical studies of O-[11C]methyl-L-tyrosine, a potential tracer for imaging amino acid transport of tumors by positron emission tomography (PET). Examinations of the radiation-absorbed dose by O-[11C]methyl-L-tyrosine and the acute toxicity and mutagenicity of O-methyl-L-tyrosine showed s...
journal_title:Nuclear medicine and biology
pub_type: 临床试验,杂志文章
doi:10.1016/j.nucmedbio.2004.11.005
更新日期:2005-04-01 00:00:00
abstract::An increasing interest in zirconium-89 (89Zr) can be attributed to the isotope's half-life which is compatible with antibody imaging using positron emission tomography (PET). The goal of this work was to develop an efficient means of production for 89Zr that provides this isotope with high radionuclidic purity and spe...
journal_title:Nuclear medicine and biology
pub_type: 杂志文章
doi:10.1016/j.nucmedbio.2017.03.004
更新日期:2017-07-01 00:00:00
abstract:INTRODUCTION:Currently, the reference method of brown adipose tissue (BAT) imaging is 18F-fluorodeoxyglucose positron emission tomography ([18F]FDG PET). BAT imaging by [18F]FDG PET requires additional stimulation process, which is inconvenient and hard to be standardized. The translocator protein 18 kDa (TSPO) PET has...
journal_title:Nuclear medicine and biology
pub_type: 杂志文章
doi:10.1016/j.nucmedbio.2020.10.001
更新日期:2020-01-01 00:00:00
abstract:INTRODUCTION:Noninvasive imaging of small animals to measure biodistributions and pharmacokinetics of radiolabeled agents is increasingly seen as an effective alternative to external counting of tissues obtained by sacrifice and dissection. However, we have observed important disagreements in measuring the accumulation...
journal_title:Nuclear medicine and biology
pub_type: 杂志文章
doi:10.1016/j.nucmedbio.2011.02.004
更新日期:2011-08-01 00:00:00
abstract::Because more and more PET centres are using small proton cyclotrons there is a renewed interest in methods for the production of electrophilic 18F by proton irradiation of [18O]O2. A method for the routine production of clinically useful quantities of [18F]F2 having a specific activity of 35 Ci/mmol has been developed...
journal_title:Nuclear medicine and biology
pub_type: 杂志文章
doi:10.1016/0969-8051(94)e0064-p
更新日期:1995-01-01 00:00:00
abstract:UNLABELLED:(99m)Tc-TRODAT-1 is the first clinical routine (99m)Tc radiopharmaceutical to evaluate dopamine neurons loss in Parkinson's disease (PD). (18)F-AV-133 is a novel PET radiotracer targeting the vesicular monoamine transporter type 2 (VMAT2) to detect monoaminergic terminal reduction in PD patients. The aim of ...
journal_title:Nuclear medicine and biology
pub_type: 杂志文章
doi:10.1016/j.nucmedbio.2013.12.017
更新日期:2014-04-01 00:00:00
abstract::[11C]Methamphetamine, a psychotropic agent, was synthesized by N-methylation of amphetamine with [11C]CH3 I in hopes that it could be applied in the near future to assist positron emission tomography (PET) in the imaging of its distribution in the human brain. The regional distribution of [11C]methamphetamine was inve...
journal_title:Nuclear medicine and biology
pub_type: 杂志文章
doi:10.1016/0969-8051(93)90080-e
更新日期:1993-05-01 00:00:00
abstract:INTRODUCTION:Nuclear and optical imaging are complementary in many aspects and there would be many advantages when optical imaging probes are prepared using radionuclides rather than classic fluorophores, and when nuclear and optical dual images are obtained using single imaging probe. METHODS:The luminescence intensi...
journal_title:Nuclear medicine and biology
pub_type: 杂志文章
doi:10.1016/j.nucmedbio.2010.09.003
更新日期:2011-04-01 00:00:00
abstract:INTRODUCTION:Thymidylate synthase and folate receptors are well-developed targets of cancer therapy. Discovery of a simple and fast method for the conversion of 11CH3Ito[11C]-formaldehyde (11CH2O) encouraged us to label the co-factor of this enzyme. Preliminary studies conducted on cell lines have demonstrated a prefer...
journal_title:Nuclear medicine and biology
pub_type: 杂志文章
doi:10.1016/j.nucmedbio.2011.12.003
更新日期:2012-07-01 00:00:00
abstract::The in vitro metabolism of 1-(4-[(18)F]fluoromethylbenzyl)-4-phenylpiperazine ([(18)F]1) and 1-(4-[(18)F]fluorobenzyl)-4-phenylpiperazine ([(18)F]2) was investigated using mouse liver S9 fraction. Results were compared to those of in vivo metabolism using mouse blood and bone and to in vitro metabolism using mouse liv...
journal_title:Nuclear medicine and biology
pub_type: 杂志文章
doi:10.1016/j.nucmedbio.2005.12.002
更新日期:2006-02-01 00:00:00
abstract::The radioiodinated (+)-p-iodovesamicol [(+)-pIV], which shows a high binding affinity for sigma-1 (sigma-1) receptors, is prepared by an exchange reaction. The specific activity (SA) is fairly low and therefore is insufficient for clinical use. In this study, we prepared (+)-[(125)I]pIV with a high SA from tributylsta...
journal_title:Nuclear medicine and biology
pub_type: 杂志文章
doi:10.1016/j.nucmedbio.2007.09.005
更新日期:2008-01-01 00:00:00
abstract::A radioiodinated ligand, (R)-N-methyl-(2-[(125)I]iodo-phenoxy)-3-phenylpropylamine, [(125)I]2-INXT, targeting norepinephrine transporters (NET), was successfully prepared. A no-carrier-added product, [(125)I]2-INXT, displayed a saturable binding with a high affinity (K(d)=0.06 nM) in the homogenates prepared from rat ...
journal_title:Nuclear medicine and biology
pub_type: 杂志文章
doi:10.1016/j.nucmedbio.2004.03.001
更新日期:2004-07-01 00:00:00
abstract:INTRODUCTION:Detection of vulnerable plaques is critically important for the selection of appropriate treatment and/or the prevention of atherosclerosis and ensuing cardiovascular diseases. In order to clarify the utility of [11C]acetate for atherosclerosis imaging, we determined the uptake and metabolism of acetate by...
journal_title:Nuclear medicine and biology
pub_type: 杂志文章
doi:10.1016/j.nucmedbio.2017.08.003
更新日期:2018-01-01 00:00:00
abstract:OBJECTIVES:To evaluate the effectiveness of PET in differentiating malignant from benign pancreatic cystic tumors. METHODS:Between 2009 and 2010, all patients with pancreatic cystic tumors who had PET, triple phase contrast computed tomography (CT) and endoscopic ultrasound (EUS) were reviewed. Clinicopathological cha...
journal_title:Nuclear medicine and biology
pub_type: 杂志文章
doi:10.1016/j.nucmedbio.2012.03.005
更新日期:2012-10-01 00:00:00
abstract::Fluorine-18 labeled 2beta-carbomethoxy-3beta-(4-chlorophenyl)-8-(2-fluoroethyl)nort ropane (FECNT) was synthesized in the development of a dopamine transporter (DAT) imaging ligand for positron emission tomography (PET). The methods of radiolabeling and ligand synthesis of FECNT, and the results of the in vitro charac...
journal_title:Nuclear medicine and biology
pub_type: 杂志文章
doi:10.1016/s0969-8051(99)00080-3
更新日期:2000-01-01 00:00:00
abstract::Using positron emission tomography (PET) and nitric oxide radiolabeled with nitrogen-13 (half-life 9.97 min) we probed the distribution and kinetics of inhaled nitric oxide in anesthetized dogs. The washout of this gas after inhalation was much slower than that observed for [13N]nitrogen gas, demonstrating its uptake ...
journal_title:Nuclear medicine and biology
pub_type: 杂志文章
doi:10.1016/0969-8051(96)00072-8
更新日期:1996-08-01 00:00:00
abstract::We report herein the preparation and biological evaluation of two radioastatinated biotin conjugates, (3-[211At]astatobenzoyl)norbiotinamide and ((5-[211At]astato-3-pyridinyl)carbonyl)norbiotinamide. Both conjugates were stable in the presence of human serum and cerebrospinal fluid as well as murine serum, indicating ...
journal_title:Nuclear medicine and biology
pub_type: 杂志文章
doi:10.1016/s0969-8051(97)00166-2
更新日期:1998-02-01 00:00:00