Abstract:
INTRODUCTION:Leukemia stem cells (LSCs) are believed to be responsible for initiating and propagating acute myeloid leukemia (AML) and for causing relapse after treatment. Radioimmunotherapy (RIT) targeting these cells may improve the treatment of AML, but is limited by the low density of target epitopes. Our objective was to study a human polynucleotide kinase/phosphatase (hPNKP) inhibitor that interferes with DNA repair as a radiosensitizer for the Auger electron RIT agent, ¹¹¹In-NLS-7G3, which recognizes the CD123⁺/CD131⁻ phenotype uniquely displayed by LSCs. METHODS:The surviving fraction (SF) of CD123⁺/CD131⁻ AML-5 cells exposed to ¹¹¹In-NLS-7G3 (33-266 nmols/L; 0.74MBq/μg) or to γ-radiation (0.25-5Gy) was determined by clonogenic assays. The effect of A12B4C3 (25 μmols/L) combined with ¹¹¹In-NLS-7G3 (16-66 nmols/L) or with γ-radiation (0.25-2Gy) on the SF of AML-5 cells was assessed. The density of DNA double-strand breaks (DSBs) in the nucleus was measured using the γ-H2AX assay. Cellular dosimetry was estimated based on the subcellular distribution of ¹¹¹In-NLS-7G3 measured by cell fractionation. RESULTS:Binding of (111)In-NLS-7G3 to AML-5 cells was reduced by 2.2-fold in the presence of an excess (1μM) of unlabeled NLS-7G3, demonstrating specific binding to the CD123⁺/CD131⁻ epitope. ¹¹¹In-NLS-7G3 reduced the SF of AML-5 cells from 86.1 ± 11.0% at 33 nmols/L to 10.5 ± 3.6% at 266 nmols/L. Unlabeled NLS-7G3 had no significant effect on the SF. Treatment of AML-5 cells with γ-radiation reduced the SF from 98.9 ± 14.9% at 0.25Gy to 0.03 ± 0.1% at 5 Gy. A12B4C3 combined with ¹¹¹In-NLS-7G3 (16-66 nmols/L) enhanced the cytotoxicity up to 1.7-fold compared to treatment with radioimmunoconjugates alone and was associated with a 1.6-fold increase in DNA DSBs in the nucleus. A12B4C3 enhanced the cytotoxicity of γ-radiation (0.25-0.5Gy) on AML-5 cells by up to 1.5-fold, and DNA DSBs were increased by 1.7-fold. Exposure to ¹¹¹In-NLS-7G3 (66 nmols/L) delivered up to 0.6Gy to AML-5 cells. CONCLUSIONS:We conclude that A12B4C3 radiosensitized AML cells to the DNA damaging effects of ¹¹¹In-NLS-7G3. Combination treatment may increase the effectiveness for Auger electron RIT of AML targeting the LSC subpopulation.
journal_name
Nucl Med Bioljournal_title
Nuclear medicine and biologyauthors
Zereshkian A,Leyton JV,Cai Z,Bergstrom D,Weinfeld M,Reilly RMdoi
10.1016/j.nucmedbio.2014.02.003subject
Has Abstractpub_date
2014-05-01 00:00:00pages
377-83issue
5eissn
0969-8051issn
1872-9614pii
S0969-8051(14)00044-4journal_volume
41pub_type
杂志文章abstract::We compared the influence of three different catechol-O-methyltransferase (COMT) inhibitors (CGP 28014, OR-611 and Ro 40-7592) on the metabolism of no-carrier-added (NCA) 6-[18F]fluoro-L-dopa (6-FDOPA) in one Rhesus monkey. All three COMT inhibitors improved 6-FDOPA availability in plasma, increased the specific uptak...
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
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:INTRODUCTION:The functions of I₂-imidazoline receptors (I₂Rs) are unknown, but evidence exists for their involvement in various neuropsychiatric disorders. Although a few positron emission tomography (PET) I₂R ligands have been developed, of which [(11)C]FTIMD and [(11)C]BU99008 were evaluated as PET I₂R imaging ligand...
journal_title:Nuclear medicine and biology
pub_type: 杂志文章
doi:10.1016/j.nucmedbio.2014.12.014
更新日期:2015-04-01 00:00:00
abstract::The advent of antibody-based cancer therapeutics has led to the concomitant rise in the development of companion diagnostics for these therapies, particularly nuclear imaging agents. A number of radioisotopes have been employed for antibody-based PET and SPECT imaging, notably ⁶⁴Cu, ¹²⁴I, ¹¹¹In, and (99m)Tc; in recent...
journal_title:Nuclear medicine and biology
pub_type: 杂志文章,评审
doi:10.1016/j.nucmedbio.2012.08.004
更新日期:2013-01-01 00:00:00
abstract::The aim of the study was to evaluate the diagnostic accuracy of scintimammography with Tc-99m MIBI for the detection of breast cancer. Patients with a suspicious lesion detected by palpation or mammography were included in the study. Excisional biopsy was performed on all patients. Mammography was performed within 3 w...
journal_title:Nuclear medicine and biology
pub_type: 临床试验,杂志文章
doi:10.1016/0969-8051(96)00084-4
更新日期:1996-08-01 00:00:00
abstract::The imaging of apoptosis represents an attractive diagnostic goal in the area of tumor therapy, degenerative diseases and organ transplantation. Since caspases play a key role during the early period of the intracellular signal cascade of cells undergoing apoptosis we considered benzyloxycarbonyl-Val-Ala-DL-Asp(O-meth...
journal_title:Nuclear medicine and biology
pub_type: 杂志文章
doi:10.1016/s0969-8051(01)00247-5
更新日期:2001-10-01 00:00:00
abstract:UNLABELLED:The purpose of this study is to reveal characteristics of (64)Cu-labeled diacetyl-bis(N(4)-methylthiosemicarbazone) ([(64)Cu]Cu-ATSM) during cell proliferation and hypoxia by autoradiography imaging and immunohistochemical staining. METHODS:The intratumoral distributions of [(64)Cu]Cu-ATSM and [(18)F]-2-flu...
journal_title:Nuclear medicine and biology
pub_type: 杂志文章
doi:10.1016/j.nucmedbio.2009.01.016
更新日期:2009-05-01 00:00:00
abstract:INTRODUCTION:Necrosis is a form of cell death that occurs in a variety of pathological conditions but can also be the result of therapy in cancer treatment. A radiotracer that could image necrotic cell death using PET could therefore be a useful tool to provide relevant information on the disease activity or therapeuti...
journal_title:Nuclear medicine and biology
pub_type: 杂志文章
doi:10.1016/j.nucmedbio.2013.04.011
更新日期:2013-08-01 00:00:00
abstract:INTRODUCTION:The use of α-emitting isotopes for radionuclide therapy is a promising treatment strategy for small micro-metastatic disease. The radioisotope (213)Bi is a nuclide that has found substantial use for targeted α-therapy (TAT). The relatively unexplored aqueous chemistry of Bi(3+), however, hinders the develo...
journal_title:Nuclear medicine and biology
pub_type: 杂志文章
doi:10.1016/j.nucmedbio.2014.12.007
更新日期:2015-05-01 00:00:00
abstract:OBJECTIVES:To compare the radiolabeling performance, stability, and practical efficacy of the chelators CHX-A″-DTPA and H4octapa with the therapeutic radiometal (90)Y. METHODS:The bifunctional chelators p-SCN-Bn-H4octapa and p-SCN-Bn-CHX-A″-DTPA were conjugated to the HER2-targeting antibody trastuzumab. The resulting...
journal_title:Nuclear medicine and biology
pub_type: 杂志文章
doi:10.1016/j.nucmedbio.2016.06.004
更新日期:2016-09-01 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:Our objective was to evaluate the effect of epidermal growth factor receptor(s) (EGFR) density on the importation and nuclear localization of 111In-labeled diethylenetriaminepentaacetic acid human epidermal growth factor ([111In]DTPA-hEGF) in breast cancer (BC) cells in vitro and in tumor xenografts and no...
journal_title:Nuclear medicine and biology
pub_type: 杂志文章
doi:10.1016/j.nucmedbio.2007.06.010
更新日期:2007-11-01 00:00:00
abstract::188Re-perrhenate has been reported effective in preventing restenosis after percutaneous transluminal coronary angioplasty. However, if the balloon ruptures, 188Re-perrhenate is released into the circulation, causing high radiation dosing to the thyroid and stomach. In this study, we evaluated the effects of perchlora...
journal_title:Nuclear medicine and biology
pub_type: 杂志文章
doi:10.1016/s0969-8051(99)00079-7
更新日期:2000-01-01 00:00:00
abstract::18Fluoro-norchloroepibatidine (exo-2-(6-fluoro-3-pyridyl)-7-azabicyclo-[2.2.1]heptane [NFEP]), a labeled derivative of epibatidine, has shown promise for imaging brain nicotinic acetylcholine receptors with PET. We determined the dose-dependent effects of NFEP in conscious rats. NFEP (1.5 microg/kg; administered intra...
journal_title:Nuclear medicine and biology
pub_type: 杂志文章
doi:10.1016/s0969-8051(97)00120-0
更新日期:1997-11-01 00:00:00
abstract:AIM:The aim was to assess the feasibility of (11)C-5-hydroxy-tryptophan positron emission tomography ((11)C-5-HTP-PET) in the follow-up after radiofrequency ablation (RFA) of liver metastases from neuroendocrine tumors (NETs). BACKGROUND:Contrast-enhanced computed tomography (CECT) and contrast-enhanced ultrasound (CE...
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
abstract:OBJECTIVES:Positron emission tomography (PET) using O-(2-[(18)F]fluoroethyl)-l-tyrosine (FET) has been successfully employed in the diagnostic workup of brain tumors. Knowledge on the mechanisms of the uptake of radiolabeled amino acids into thyroidal tissues and well-differentiated thyroid carcinomas is limited. We th...
journal_title:Nuclear medicine and biology
pub_type: 杂志文章
doi:10.1016/j.nucmedbio.2006.12.007
更新日期:2007-04-01 00:00:00
abstract::3-Amino-4-(2-dimethylaminomethyl-phenylsulfanyl)-benzonitrile, labeled with carbon-11 ([11C]-DASB), is a recently introduced radiotracer for imaging the serotonin transporter (SERT) by positron emission tomography (PET). A series of in vitro and in vivo experiments were performed to further characterise the properties...
journal_title:Nuclear medicine and biology
pub_type: 杂志文章
doi:10.1016/s0969-8051(02)00316-5
更新日期:2002-07-01 00:00:00
abstract:INTRODUCTION:Radiolabeled 2-nitroimidazoles (azomycins) are a prominent class of biomarkers for PET imaging of hypoxia. [18F]Fluoro-azomycin-α-arabinoside ([18F]FAZA) - already in clinical use - may be seen as α-configuration nucleoside, but enters cells only via diffusion and is not transported by cellular nucleoside ...
journal_title:Nuclear medicine and biology
pub_type: 杂志文章
doi:10.1016/j.nucmedbio.2016.08.005
更新日期:2016-12-01 00:00:00
abstract::Structural variations of the nicotinic acetylcholine receptor radioligand N-[(11)C]methyl-epibatidine were made to form (11)C-labeled N-methyl-norchloroepibatidine (N-methyl-NorchloroEPB) and N-methyl-2-(2-pyridyl)-7-azabicyclo[2.2.1]heptane (N-methyl-2PABH). Radiosyntheses were performed by methylation with high radi...
journal_title:Nuclear medicine and biology
pub_type: 杂志文章
doi:10.1016/s0969-8051(00)00080-9
更新日期:2000-04-01 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::The uptake, retention and tissue to blood ratios of two non-steroidal, 125I-labeled iodoestrogens, an iodotrihydroxyphenylethylene, 2-iodo-1,2-bis(4-hydroxyphenyl)-2-(3-hydroxyphenyl)ethylene and an iododihydroxyphenylethylene, 2-iodo-1,1-bis(4-hydroxyphenyl)-2-phenylethylene, were compared after intraperitoneal injec...
journal_title:Nuclear medicine and biology
pub_type: 杂志文章
doi:10.1016/0969-8051(95)00002-f
更新日期:1995-07-01 00:00:00
abstract:OBJECTIVE:Pretargeting is the concept that combines optimal delivery of the antibody and rapid capture and elimination of the radioactivity. In this study, we evaluated the potential of antibody pretargeting to enable the tumor-targeting (212)Pb for in vivo generation of (212)Bi for alpha particle radiotherapy. METHOD...
journal_title:Nuclear medicine and biology
pub_type: 杂志文章
doi:10.1016/j.nucmedbio.2005.06.009
更新日期:2005-10-01 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:INTRODUCTION:Targeted alpha therapy (TAT) has the potential for killing micro-metastases with minimum collateral damage to surrounding healthy tissue. In-vivo generator radionuclides, such as(223)Ra, (225)Ra, and (225)Ac, are of special interest for radiotherapeutic applications as they emit multiple α-particles during...
journal_title:Nuclear medicine and biology
pub_type: 杂志文章
doi:10.1016/j.nucmedbio.2015.03.007
更新日期:2015-07-01 00:00:00
abstract:OBJECTIVE:The goal of this study was to measure functional and structural aspects of local neuroinflammation induced by intracerebral injection of lipopolysaccharide (LPS) in rats using TSPO microPET imaging with [(18)F]DPA-714, magnetic resonance imaging (MRI), in vitro autoradiography and immunohistochemistry (IHC) i...
journal_title:Nuclear medicine and biology
pub_type: 杂志文章
doi:10.1016/j.nucmedbio.2015.06.010
更新日期:2015-10-01 00:00:00
abstract:INTRODUCTION:Gonadotropin releasing hormone (GnRH) receptor is overexpressed in many human tumors. Previously we developed a 18F-labelled GnRH peptide. Although the GnRH-targeted PET probe can be clearly visualized by microPET imaging in a PC-3 xenograft model, clinical applications of the probe have been limited by co...
journal_title:Nuclear medicine and biology
pub_type: 杂志文章
doi:10.1016/j.nucmedbio.2020.02.004
更新日期:2020-01-01 00:00:00
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-iodophenyl...
journal_title:Nuclear medicine and biology
pub_type: 杂志文章
doi:10.1016/j.nucmedbio.2005.01.008
更新日期:2005-05-01 00:00:00
abstract::An in vivo estimation of the newly synthesized MAO-A specific inhibitor, [125I]-labeled N-[3(2,4-dichloro-6-iodophenoxy)propyl]-N-methyl-2- propynylamine ([125I]-iodoclorgyline), was performed. Retention of the radioactivity of this radioligand was observed in the brain from 1 h post-injection. Pretreatments with clor...
journal_title:Nuclear medicine and biology
pub_type: 杂志文章
doi:10.1016/0969-8051(94)00105-s
更新日期:1995-02-01 00:00:00
abstract::We examined transport of 3-[(125)I]iodo-alpha-methyl-L-tyrosine ([(125)I]IMT) in Xenopus laevis oocytes co-expressing human L-type amino acid transporter 1 (a component of system L) and human 4F2hc. Human LAT1 mediated transport of [(125)I]IMT. [(125)I]IMT uptake was decreased by the presence of L-isomers of Cys, Leu,...
journal_title:Nuclear medicine and biology
pub_type: 杂志文章
doi:10.1016/s0969-8051(02)00350-5
更新日期:2003-01-01 00:00:00
abstract::The imaging of the distribution of beta-amyloid (Abeta) plaques in the brain is becoming an important diagnostic modality in Alzheimer's disease (AD). Here, we synthesized novel benzothiophene derivatives and labeled them with (18)F for the potential diagnostic imaging of AD patients using positron emission tomography...
journal_title:Nuclear medicine and biology
pub_type: 杂志文章
doi:10.1016/j.nucmedbio.2006.06.006
更新日期:2006-08-01 00:00:00