Abstract:
INTRODUCTION:HDAC6, a structural and functional distinct member of the HDAC-family, shows great promise as a target to treat several cancers and neurodegenerative diseases. Several clinical trials are evaluating HDAC6 inhibitors in solid tumours and haematological malignancies, but so far no HDAC6 inhibitor has received marketing authorisation. The availability of an HDAC6-specific PET tracer can potentially aid in cancer diagnosis, select patients for HDAC6 inhibitor treatment and accelerate HDAC6 drug development. We have evaluated the HDAC6 PET tracer [11C]KB631, in vitro and in vivo in B16.F10 melanoma inoculated mice. METHODS:In vitro binding specificity was evaluated by autoradiography studies on rodent brain, B16.F10 melanoma and PC3 prostate carcinoma cryosections. Biodistribution and quantification of plasma radio-metabolites was determined in NMRI-mice in control conditions and after blocking with KB631, Ricolinostat and SAHA. Tracer tumour uptake was evaluated in B16.F10 melanoma inoculated C57BL/6 mice. RESULTS:In vitro autoradiography studies showed HDAC6-selective binding to rodent brain, B16.F10 melanoma and PC3 prostate carcinoma tissue slices. Tracer binding in several organs of interest could be partially blocked in NMRI-mice pre-treated with KB631, Ricolinostat or SAHA, indicating specific tracer binding. A biodistribution and 90-min dynamic μPET study on B16.F10 melanoma mice, pre-treated with vehicle or Ricolinostat (50 mg/kg), indicated HDAC6-specific tumour uptake. CONCLUSIONS:[11C]KB631 shows HDAC6-selective binding in mouse B16.F10 melanoma tumours in vitro and in vivo. [11C]KB631 PET can be used for in vivo investigation of the expression of HDAC6 in tumours. ADVANCES IN KNOWLEDGE: [11C]KB631 shows increased expression of HDAC6 in mouse B16.F10 melanoma tumours and can be used to visualise target engagement of HDAC6 inhibitors.
journal_name
Nucl Med Bioljournal_title
Nuclear medicine and biologyauthors
Vermeulen K,Ahamed M,Luyten K,Bormans Gdoi
10.1016/j.nucmedbio.2019.05.004subject
Has Abstractpub_date
2019-01-01 00:00:00pages
1-11eissn
0969-8051issn
1872-9614pii
S0969-8051(19)30083-6journal_volume
74-75pub_type
杂志文章abstract::With [11C]raclopride,[11C]nemonapride and [11C]N-methylspiperone, degeneration of dopamine D2-like receptors in the unilaterally quinolinic acid-lesioned rats was evaluated by positron emission tomography (PET) and ex vivo and in vitro autoradiography. PET showed a decreased uptake of [11C]raclopride in the lesioned s...
journal_title:Nuclear medicine and biology
pub_type: 杂志文章
doi:10.1016/s0969-8051(01)00307-9
更新日期:2002-04-01 00:00:00
abstract::We have previously performed quantitative kinetic modeling of [(123)I]CNS 1261, a new SPET ligand for the MK801 intrachannel site of the NMDA receptor. We now report a bolus-infusion protocol, which eliminates the need for arterial blood sampling. Dynamic SPET scanning and venous blood sampling were performed in 7 hea...
journal_title:Nuclear medicine and biology
pub_type: 临床试验,杂志文章
doi:10.1016/j.nucmedbio.2003.08.008
更新日期:2004-02-01 00:00:00
abstract:INTRODUCTION:Severe brain hypoxia in the territory of the occluded artery is a key feature of ischemic stroke. This region can be imaged using positron emission tomography (PET) and the standard hypoxia radiotracer (18)F-fluoromisonidazole ((18)F-FMISO). However, the utility of (18)F-FMISO is limited by its slow accumu...
journal_title:Nuclear medicine and biology
pub_type: 杂志文章
doi:10.1016/j.nucmedbio.2012.11.012
更新日期:2013-04-01 00:00:00
abstract::PET centers without particle accelerators make clinical PET widely available at reduced cost. For myocardial perfusion tracers, these satellite PET centers are limited to generator- produced 82Rb(+) and 62Cu[PTSM]. Their limitations motivate a search for transportable alternatives. In search of new tracers we have syn...
journal_title:Nuclear medicine and biology
pub_type: 杂志文章
doi:10.1016/s0969-8051(01)00233-5
更新日期:2001-08-01 00:00:00
abstract:UNLABELLED:[(18)F]-labelled choline analogues, such as 2-[(18)F]fluoroethylcholine ((18)FECH), have suggested to be a new class of choline derivatives highly useful for the imaging of prostate and brain tumours. In fact, tumour cells with enhanced proliferation rate usually exhibit an improved choline uptake due to the...
journal_title:Nuclear medicine and biology
pub_type: 杂志文章
doi:10.1016/j.nucmedbio.2009.12.009
更新日期:2010-04-01 00:00:00
abstract:OBJECTIVE:Hepatic stellate cell (HSC) activation, which is accompanied by increased expression of integrin αvβ3, is an important factor in liver fibrogenesis. Molecular imaging targeting the integrin αvβ3 could provide a non-invasive method for evaluating the expression and the function of the integrin αvβ3 on the acti...
journal_title:Nuclear medicine and biology
pub_type: 杂志文章
doi:10.1016/j.nucmedbio.2014.11.007
更新日期:2015-03-01 00:00:00
abstract::Melanin, a natural biological pigment present in many organisms, has been found to exhibit multiple functions. An important property of melanin is its ability to chelate metal ions strongly, which might be developed as an iron chelator for iron overload therapy. Herein, we prepared the ultrasmall water-soluble melanin...
journal_title:Nuclear medicine and biology
pub_type: 杂志文章
doi:10.1016/j.nucmedbio.2016.05.014
更新日期:2016-09-01 00:00:00
abstract:INTRODUCTION:Radiopharmaceuticals that can bind selectively the kappa-opioid receptor may present opportunities for staging clinical brain disorders and evaluating the efficiency of new therapies related to stroke, neurodegenerative diseases or opiate addiction. The N-methylated derivative of JDTic (named MeJDTic), whi...
journal_title:Nuclear medicine and biology
pub_type: 杂志文章
doi:10.1016/j.nucmedbio.2008.02.010
更新日期:2008-07-01 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::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: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::A consensus has emerged that early imaging (within 20 min post-injection [p.i.] of sestamibi) has the highest diagnostic yield. Tc-99m-sestamibi uptake has been associated with P-glycoprotein-mediated multi-drug resistance (MDR), tumor vascularization, invasiveness, and cell proliferation. The aim of this study was to...
journal_title:Nuclear medicine and biology
pub_type: 临床试验,杂志文章
doi:10.1016/s0969-8051(98)00026-2
更新日期:1998-08-01 00:00:00
abstract::We propose a renal imaging agent, the 99mTc complex of the bidentate-N,S chelate N-(mercaptoacetyl)glycine (99mTc-2GAM), with the imaging characteristics of 99mTc-DMSA but a faster kidney uptake; chemical evidence supports the formulation of 99mTc-2GAM as [Tc(v)(O)(GAM)2]-. After biodistribution and toxicity studies i...
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
abstract:PURPOSE:The aim of this study was to investigate the biodistribution and localization of an anti-inflammatory nonapeptide coupled to synovial targeting peptide (HAP-1) in rat adjuvant-induced arthritis. PROCEDURE:N(ε)-functionalized histidine derivative was coupled to the N-terminus of core peptide (CP) and HAP-1 to a...
journal_title:Nuclear medicine and biology
pub_type: 杂志文章
doi:10.1016/j.nucmedbio.2011.01.007
更新日期:2011-07-01 00:00:00
abstract::The Cu(I)-assisted aromatic halogen exchange proved useful for preparation of macroscopic amounts of 2-iodophenyl-metyrapone as well as for the n.c.a. radioiodinated analogue. Semi-preparative HPLC-isolation provided the compound with high purity for use as chromatographic standard and for the determination of the inh...
journal_title:Nuclear medicine and biology
pub_type: 杂志文章
doi:10.1016/0969-8051(95)02033-0
更新日期:1995-11-01 00:00:00
abstract::Liver accumulation of 99mTc-DL-homocysteine (99mTc-Hcy), which had been found to accumulate in several experimental tumors, was studied using experimental hepatitis models of rats. The distribution of this compound in liver of rats treated with CCl4 (25-100 microL/100 g body weight) was more than five times higher tha...
journal_title:Nuclear medicine and biology
pub_type: 杂志文章
doi:10.1016/0969-8051(93)90091-8
更新日期:1993-11-01 00:00:00
abstract:INTRODUCTION:(99m)Tc-BnAO is one of the nonnitroimidazole hypoxia markers with the highest citation and could be potentially useful in both oncology and other clinical applications. However, it appears inferior in vitro due to lower absolute accumulation and smaller anoxic/normoxic uptake ratio. It is possible that the...
journal_title:Nuclear medicine and biology
pub_type: 杂志文章
doi:10.1016/j.nucmedbio.2009.09.003
更新日期:2010-02-01 00:00:00
abstract:UNLABELLED:Gastrin-releasing peptide receptors (GRPr) are a member of the bombesin (BBN) receptor family. GRPr are expressed in high numbers on specific human cancers, including human prostate cancer. Therefore, copper-64 ((64)Cu) radiolabeled BBN(7-14)NH(2) conjugates could have potential for diagnosis of human prosta...
journal_title:Nuclear medicine and biology
pub_type: 杂志文章
doi:10.1016/j.nucmedbio.2010.04.016
更新日期:2010-10-01 00:00:00
abstract::[¹⁸F]FMISO is the most widely validated PET radiotracer for imaging hypoxic tissue. However, as a result of the pharmacokinetics of [¹⁸F]FMISO a 2h wait between tracer administration and patient scanning is required for optimal image acquisition. In order to develop hypoxia imaging agents with faster kinetics, we have...
journal_title:Nuclear medicine and biology
pub_type: 杂志文章
doi:10.1016/j.nucmedbio.2014.03.001
更新日期:2014-05-01 00:00:00
abstract:INTRODUCTION:Several 11C and 18F labeled 3,4-dihydroxy-l-phenylalanine (l-DOPA) analogues have been used for neurologic and oncologic diseases, especially for brain tumors and neuroendocrine tumors PET imaging. However, 18F-labeled N-substituted l-DOPA analogues have not been reported so far. In the current study, radi...
journal_title:Nuclear medicine and biology
pub_type: 杂志文章
doi:10.1016/j.nucmedbio.2017.04.002
更新日期:2017-07-01 00:00:00
abstract::To improve standardization in analytical reagents we investigated Chloramine-T radioiodination (125I) of several biomolecules based on the use of a single amount of the oxidizing agent Chloramine-T as the limiting reagent being exhausted during the course of the reaction. Whenever the labeling yield resulted in less t...
journal_title:Nuclear medicine and biology
pub_type: 杂志文章
doi:10.1016/s0969-8051(01)00261-x
更新日期:2001-11-01 00:00:00
abstract::The in vitro stability and animal pharmacokinetics of 99mTc bound to Sandoz and C110 IgG antibodies via a modified MAG3 has been compared with the hydrazino nicotinamide (SHNH) moiety as standard. For both antibodies, the stabilities of the label to challenge at up to 50:1 cysteine: IgG molar ratio were comparable, bu...
journal_title:Nuclear medicine and biology
pub_type: 杂志文章
doi:10.1016/s0969-8051(96)00131-x
更新日期:1996-10-01 00:00:00
abstract::Technetium-99m-modified polylysine (MPL) is a mild and efficient method for cell labeling that is easily applicable to human lymphocytes. 99mTc-MPL uptake is maximal in 40 min at room temperature. Cell labeling efficiency (from 60 to 80%) increases with rising concentrations of cells and labeling agent. In vitro stabi...
journal_title:Nuclear medicine and biology
pub_type: 杂志文章
doi:10.1016/0969-8051(95)02011-x
更新日期:1996-01-01 00:00:00
abstract::By variation of reaction parameters iodination of 3-(9,10-didehydro-6-methyl-8 alpha-ergolinyl)-1,1-diethylurea (lisuride) was performed with the radiohalogen [123I]iodine (t1/2 = 13.3 h). For comparative experiments and stability studies the beta(-)-emitting radioisotope [131I]iodine (t1/2 = 8.04 d) was also used. Re...
journal_title:Nuclear medicine and biology
pub_type: 杂志文章
doi:10.1016/0969-8051(96)00018-2
更新日期:1996-04-01 00:00:00
abstract:INTRODUCTION:Image-derived input functions (IDIFs) represent a promising non-invasive alternative to arterial blood sampling for quantification in positron emission tomography (PET) studies. However, routine applications in patients and longitudinal designs are largely missing despite widespread attempts in healthy sub...
journal_title:Nuclear medicine and biology
pub_type: 临床试验,杂志文章
doi:10.1016/j.nucmedbio.2012.12.011
更新日期:2013-04-01 00:00:00
abstract:INTRODUCTION:Progesterone receptors (PRs) are present in many breast tumors, and their levels are increased by certain endocrine therapies. They can be used as targets for diagnostic imaging and radiotherapy. METHOD:16alpha,17alpha-[(R)-1'-alpha-(5-[(76)Br]Bromofurylmethylidene)dioxyl]-21-hydroxy-19-norpregn-4-ene-3,2...
journal_title:Nuclear medicine and biology
pub_type: 杂志文章
doi:10.1016/j.nucmedbio.2008.05.001
更新日期:2008-08-01 00:00:00
abstract::To evaluate the ability of [1-11C]octanoate as a PET tracer for imaging the brain, we examined its distribution in the brain and surrounding tissues in rats and cats with PET. In rats, owing to the accumulated radioactivity in the harderian glands, clear brain images were not obtained at rostral levels. In cats, the b...
journal_title:Nuclear medicine and biology
pub_type: 杂志文章
doi:10.1016/s0969-8051(96)00148-5
更新日期:1996-11-01 00:00:00
abstract:INTRODUCTION:Dedifferentiated thyroid cancer is often incurable because it does not respond to radioiodine. This study aimed to investigate iodide uptake and the expressions of thyroid-specific molecules after the transfection of human thyrotropin receptor (hTSHR) gene in poorly differentiated follicular thyroid cancer...
journal_title:Nuclear medicine and biology
pub_type: 杂志文章
doi:10.1016/j.nucmedbio.2012.12.004
更新日期:2013-05-01 00:00:00
abstract:UNLABELLED:In recent years, several PET and SPECT studies have shown loss of striatal dopamine transporter (DAT) binding in amphetamine (AMPH) users. However, the use of DAT SPECT tracers to detect AMPH-induced changes in DAT binding has not been validated. We therefore examined if repeated administration of D-AMPH or ...
journal_title:Nuclear medicine and biology
pub_type: 杂志文章
doi:10.1016/j.nucmedbio.2005.12.007
更新日期:2006-04-01 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