Abstract：
:In humans, C-X-C chemokine receptor type 4 (CXCR4) is a protein that is encoded by the CXCR4 gene and binds the ligand CXCL12 (also known as SDF-1). The CXCR4-CXCL12 interaction in cancer elicits biological activities that result in tumor progression and has accordingly been the subject of significant investigation for detection and treatment of the disease. Peptidic antagonists have been labeled with a variety of radioisotopes for the detection of CXCR4, but the methodology utilizing small molecules has predominantly used radiometals. We report here the development of a 18F-radiolabeled cyclam-based small molecule radioprobe, [18F]MCFB, for imaging CXCR4 expression. The IC50 value of [19F]MCFB for CXCR4 was similar to that of AMD3465 (111.3 and 89.8 nM, respectively). In vitro binding assays show that the tracer depicted a differential CXCR4 expression, which was blocked in the presence of AMD3465, demonstrating the specificity of [18F]MCFB. Positron emission tomography (PET) imaging studies showed a distinct uptake of the radioprobe in lymphoma and breast cancer xenografts. High liver and kidney uptakes were seen with [18F]MCFB, leading us to further examine the basis of its pharmacokinetics in relation to the tracer's cationic nature and thus the role of organic cation transporters (OCTs). Substrate competition following the intravenous injection of metformin led to a marked decrease in the urinary excretion of [18F]MCFB, with moderate changes observed in other organs, including the liver. Our results suggest involvement of OCTs in the renal elimination of the tracer. In conclusion, the 18F-radiolabeled monocyclam, [18F]MCFB, has potential to detect tumor CXCR4 in nonhepatic tissues.
journal_name
Mol Pharmjournal_title
Molecular pharmaceuticsauthors
Brickute D,Braga M,Kaliszczak MA,Barnes C,Lau D,Carroll L,Stevens E,Trousil S,Alam IS,Nguyen QD,Aboagye EOdoi
10.1021/acs.molpharmaceut.9b00069subject
Has Abstractpub_date
2019-05-06 00:00:00pages
2106-2117issue
5eissn
1543-8384issn
1543-8392journal_volume
16pub_type
杂志文章abstract：:Microspheres of bovine serum albumin (BSA) and silk fibroin are produced by applying ultrasound in a biphasic system consisting of an aqueous protein solution and an organic solvent. The protein microspheres are dispersed in an aqueous media where the protein remains at the interface covering the organic solvent. This...
journal_title：Molecular pharmaceutics
pub_type： 杂志文章
doi：10.1021/mp3001827
更新日期：2012-11-05 00:00:00
abstract：:The weak base memantine is actively secreted into urine, however the underlying mechanisms are insufficiently understood. Potential candidates involved in memantine renal secretion are organic cation transporter 2 (OCT2) and multidrug and toxin extrusion proteins (MATE1, MATE2-K). The aim of this in vitro study was th...
journal_title：Molecular pharmaceutics
pub_type： 杂志文章
doi：10.1021/acs.molpharmaceut.7b00179
更新日期：2017-09-05 00:00:00
abstract：:Water-soluble camptothecin (CPT)-polyoxetane conjugates were synthesized using a clickable polymeric platform P(EAMO) that was made by polymerization of acetylene-functionalized 3-ethyl-3-(hydroxymethyl)oxetane (i.e., EAMO). CPT was first modified with a linker 6-azidohexanoic acid via an ester linkage to yield CPT-az...
journal_title：Molecular pharmaceutics
pub_type： 杂志文章
doi：10.1021/mp3005066
更新日期：2012-11-05 00:00:00
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journal_title：Molecular pharmaceutics
pub_type： 杂志文章
doi：10.1021/mp3003557
更新日期：2013-01-07 00:00:00
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journal_title：Molecular pharmaceutics
pub_type： 杂志文章
doi：10.1021/acs.molpharmaceut.7b01114
更新日期：2018-03-05 00:00:00
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journal_title：Molecular pharmaceutics
pub_type： 杂志文章
doi：10.1021/acs.molpharmaceut.5b00168
更新日期：2015-09-08 00:00:00
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journal_title：Molecular pharmaceutics
pub_type： 杂志文章
doi：10.1021/acs.molpharmaceut.7b00220
更新日期：2017-08-07 00:00:00
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journal_title：Molecular pharmaceutics
pub_type： 杂志文章
doi：10.1021/mp300305f
更新日期：2012-11-05 00:00:00
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journal_title：Molecular pharmaceutics
pub_type： 杂志文章
doi：10.1021/mp300338s
更新日期：2012-12-03 00:00:00
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journal_title：Molecular pharmaceutics
pub_type： 杂志文章
doi：10.1021/mp400677y
更新日期：2014-07-07 00:00:00
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pub_type： 杂志文章
doi：10.1021/acs.molpharmaceut.0c00562
更新日期：2020-10-05 00:00:00
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journal_title：Molecular pharmaceutics
pub_type： 杂志文章
doi：10.1021/mp300237z
更新日期：2012-10-01 00:00:00
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journal_title：Molecular pharmaceutics
pub_type： 杂志文章
doi：10.1021/mp200133s
更新日期：2011-10-03 00:00:00
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pub_type： 杂志文章
doi：10.1021/acs.molpharmaceut.6b01124
更新日期：2017-05-01 00:00:00
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pub_type： 杂志文章
doi：10.1021/acs.molpharmaceut.6b00438
更新日期：2016-09-06 00:00:00
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journal_title：Molecular pharmaceutics
pub_type： 杂志文章
doi：10.1021/mp200629s
更新日期：2012-04-02 00:00:00
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journal_title：Molecular pharmaceutics
pub_type： 杂志文章
doi：10.1021/mp300410n
更新日期：2013-03-04 00:00:00
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pub_type： 杂志文章
doi：10.1021/acs.molpharmaceut.7b00404
更新日期：2017-11-06 00:00:00
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doi：10.1021/mp400371r
更新日期：2013-12-02 00:00:00
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pub_type： 杂志文章
doi：10.1021/acs.molpharmaceut.5b00875
更新日期：2016-04-04 00:00:00
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更新日期：2014-03-03 00:00:00
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journal_title：Molecular pharmaceutics
pub_type： 杂志文章
doi：10.1021/acs.molpharmaceut.7b00996
更新日期：2018-03-05 00:00:00
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更新日期：2009-03-01 00:00:00
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journal_title：Molecular pharmaceutics
pub_type： 杂志文章
doi：10.1021/acs.molpharmaceut.6b00264
更新日期：2016-07-05 00:00:00
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journal_title：Molecular pharmaceutics
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doi：10.1021/mp300633f
更新日期：2014-02-03 00:00:00
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doi：10.1021/mp100049m
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pub_type： 杂志文章
doi：10.1021/acs.molpharmaceut.7b00475
更新日期：2017-10-02 00:00:00
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journal_title：Molecular pharmaceutics
pub_type： 杂志文章
doi：10.1021/acs.molpharmaceut.8b01078
更新日期：2019-03-04 00:00:00
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journal_title：Molecular pharmaceutics
pub_type： 杂志文章
doi：10.1021/acs.molpharmaceut.6b00217
更新日期：2016-07-05 00:00:00
