Abstract:
:The pyridopyrimidinones are a potent class of inhibitors of c-Abl kinase and Bcr-Abl kinase, the causative fusion protein in chronic myelogenous leukemia and Src family kinases. A novel method for routine, high-yield no-carrier-added synthesis of [(124)I]-, [(125)I]- and [(131)I]-6-(2,6-dichlorophenyl)-2-(4-iodophenylamino)-8-methyl-8H-pyrido[2,3-d]pyrimidin-7-one has been developed. The 4'-trimethylstannyl- or 4'-tri-n-butylstannyl-pyridopyrimidinone precursors were prepared from the aryl bromide via a palladium-mediated coupling with hexaalkylditin (dioxane/microwave irradiation/10 min at 160 degrees C). The radioiodination of 4'-stannylpyridopyrimidinones was found to optimally occur via an iododestannylation with Na(124)I, Na(125)I or Na(131)I in the presence of an oxidant [30% H(2)O(2)/HOAc (1:3)/10 min] in 79-87% radiochemical yield with >99% radiochemical purity. The total radiosynthesis time was 30 min. The 4-iodophenylpyridopyrimidinone 2 inhibited recombinant Abl kinase activity with an IC(50) of 2.0 nM. Cell proliferation of K562 and A431 cells was inhibited with an IC(50) of 2.0 and 20 nM, respectively. Rapid cellular uptake and equilibrium were observed within 10-15 min using [(131)I]-4-iodophenylpyridopyrimidinone 6c in K562 and A431 cells and demonstrated a 2.8-fold uptake selectivity for the Bcr-Abl-expressing K562 cells at 60 min. These results suggest that pyridopyrimidinone radiotracers may be useful in imaging Abl-, Bcr-Abl- or Src-expressing malignancies.
journal_name
Nucl Med Bioljournal_title
Nuclear medicine and biologyauthors
Veach DR,Namavari M,Beresten T,Balatoni J,Minchenko M,Djaballah H,Finn RD,Clarkson B,Gelovani JG,Bornmann WG,Larson SMdoi
10.1016/j.nucmedbio.2005.01.008keywords:
subject
Has Abstractpub_date
2005-05-01 00:00:00pages
313-21issue
4eissn
0969-8051issn
1872-9614pii
S0969-8051(05)00048-Xjournal_volume
32pub_type
杂志文章abstract:INTRODUCTION:3'-Deoxy-3'-[(18)F]fluorothymidine ([(18)F]FLT) shows great potential as a tracer for proliferative studies with PET. However, its regular application is often limited by low radiochemical yields and the use of a troublesome HPLC separation. Moreover, a high content of ethanol, at least one-fold higher tha...
journal_title:Nuclear medicine and biology
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doi:10.1016/j.nucmedbio.2011.10.005
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journal_title:Nuclear medicine and biology
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journal_title:Nuclear medicine and biology
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journal_title:Nuclear medicine and biology
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journal_title:Nuclear medicine and biology
pub_type: 临床试验,杂志文章
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更新日期:1999-11-01 00:00:00
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journal_title:Nuclear medicine and biology
pub_type: 杂志文章
doi:10.1016/s0969-8051(00)00201-8
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journal_title:Nuclear medicine and biology
pub_type: 杂志文章
doi:10.1016/j.nucmedbio.2004.10.004
更新日期:2005-02-01 00:00:00
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journal_title:Nuclear medicine and biology
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pub_type: 杂志文章
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更新日期:2001-04-01 00:00:00
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journal_title:Nuclear medicine and biology
pub_type: 临床试验,杂志文章
doi:10.1016/j.nucmedbio.2011.12.013
更新日期:2012-08-01 00:00:00
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journal_title:Nuclear medicine and biology
pub_type: 杂志文章
doi:10.1016/0969-8051(94)90125-2
更新日期:1994-01-01 00:00:00
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pub_type: 杂志文章
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更新日期:2020-11-28 00:00:00
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pub_type: 杂志文章
doi:10.1016/0969-8051(96)00115-1
更新日期:1996-08-01 00:00:00
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journal_title:Nuclear medicine and biology
pub_type: 杂志文章
doi:10.1016/j.nucmedbio.2004.07.003
更新日期:2004-11-01 00:00:00
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journal_title:Nuclear medicine and biology
pub_type: 杂志文章
doi:10.1016/j.nucmedbio.2011.05.010
更新日期:2011-11-01 00:00:00
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journal_title:Nuclear medicine and biology
pub_type: 杂志文章
doi:10.1016/j.nucmedbio.2006.12.001
更新日期:2007-02-01 00:00:00
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pub_type: 杂志文章
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journal_title:Nuclear medicine and biology
pub_type: 杂志文章
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更新日期:1995-05-01 00:00:00
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journal_title:Nuclear medicine and biology
pub_type: 杂志文章
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更新日期:1995-08-01 00:00:00
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journal_title:Nuclear medicine and biology
pub_type: 杂志文章
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更新日期:2001-04-01 00:00:00
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更新日期:2013-08-01 00:00:00
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journal_title:Nuclear medicine and biology
pub_type: 杂志文章
doi:10.1016/j.nucmedbio.2010.02.001
更新日期:2010-05-01 00:00:00
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journal_title:Nuclear medicine and biology
pub_type: 杂志文章
doi:10.1016/s0969-8051(97)00025-5
更新日期:1997-07-01 00:00:00
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journal_title:Nuclear medicine and biology
pub_type: 杂志文章
doi:10.1016/0969-8051(95)00010-u
更新日期:1995-08-01 00:00:00
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journal_title:Nuclear medicine and biology
pub_type: 杂志文章
doi:10.1016/s0969-8051(96)00135-7
更新日期:1996-11-01 00:00:00
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journal_title:Nuclear medicine and biology
pub_type: 杂志文章
doi:10.1016/0969-8051(95)00032-s
更新日期:1995-10-01 00:00:00
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journal_title:Nuclear medicine and biology
pub_type: 杂志文章,评审
doi:10.1016/0969-8051(94)90073-6
更新日期:1994-04-01 00:00:00
abstract:INTRODUCTION:Ultrasound (US) contrast agents based on microbubbles (MBs) are being investigated as platforms for drug and gene delivery. A methodology for determining the distribution and fate of modified MBs quantitatively in vivo can be achieved by tagging MBs directly with (99m)Tc. This creates the opportunity to em...
journal_title:Nuclear medicine and biology
pub_type: 杂志文章
doi:10.1016/j.nucmedbio.2011.04.008
更新日期:2011-11-01 00:00:00
abstract::Ex vivo and in vitro autoradiography (ARG) with radioluminography is a useful technique to characterize newly developed 11C-labeled positron emission tomography (PET) tracers and to apply them to biological and pharmacological studies. In this report, we have described a method of evaluating the radioactivity distribu...
journal_title:Nuclear medicine and biology
pub_type: 杂志文章
doi:10.1016/s0969-8051(98)00115-2
更新日期:1999-04-01 00:00:00