Preparation of a multi-modal agent for sentinel lymph node mapping using Evans blue and 99mTc-labeled mannosylated human serum albumin conjugate.

Abstract:

INTRODUCTION:The identification of sentinel lymph nodes (SLNs) is important in deciding the resection range during surgery. 99mTc-labeled mannosylated human serum albumin ([99mTc]Tc-MSA) is a radiopharmaceutical developed for SLN detection by targeting macrophages. Evans blue (EB) is a blue dye binding strongly to albumin and has been used for SLN detection. [99mTc]Tc-MSA-EB conjugate was prepared as a multi-modal imaging agent and tested its performance by visual investigation, fluorescence imaging and SPECT/CT for SLN mapping in mice. METHODS:EB was mixed with various concentration of MSA to prepare MSA-EB conjugates. The binding efficiencies were determined using thin-layer chromatography. The UV-VIS spectra and molar extinction coefficient of the conjugate were obtained. The fluorescence was monitored at the excitation wavelength range 420-780 nm and the emission wavelength range 520-845 nm. The [99mTc]Tc-MSA-EB conjugate and EB were injected into the footpads of normal BALB/c mice to check the lymph node (LN) uptakes. The visible, fluorescence, and SPECT/CT images were obtained after injection. RESULTS:The conjugation of EB with MSA increased by time and was saturated within 10 min. The molar extinction coefficient of the conjugate was 99,259.3/M/cm at 620 nm. The uptake of conjugate into the popliteal LN after injection into the footpads of mice was investigated visually and fluorescence imaging. SPECT/CT images showed that the standardized uptake values of [99mTc]Tc-MSA-EB conjugate in popliteal LN were about 4 times higher than in sciatic LN at all timepoints. It was confirmed by investigating resected LN that the blue color, fluorescence, and radioactivity of the [99mTc]Tc-MSA-EB conjugate were retained only on the LN and did not spread to adjoining tissues. CONCLUSION:[99mTc]Tc-MSA-EB conjugate has a great potential as a multi-modal SLN mapping agent which could be detected by visual investigation, fluorescence imaging, and SPECT/CT.

journal_name

Nucl Med Biol

authors

Lee JY,Kim HY,Lee YS,Seo HY,Park JY,Jeong JM

doi

10.1016/j.nucmedbio.2020.02.002

subject

Has Abstract

pub_date

2020-01-01 00:00:00

pages

38-45

eissn

0969-8051

issn

1872-9614

pii

S0969-8051(19)30489-5

journal_volume

84-85

pub_type

杂志文章
  • Synthesis of [11C]interleukin 8 using a cell-free translation system and L-[11C]methionine.

    abstract::Positron emission tomography (PET), which requires a compound labeled with a positron emitter radioisotope as an imaging probe, is one of the most useful and valuable imaging modalities in molecular imaging. It has several advantages over other imaging modalities, particularly in sensitive and quantitative investigati...

    journal_title:Nuclear medicine and biology

    pub_type: 杂志文章

    doi:10.1016/j.nucmedbio.2011.07.005

    authors: Harada R,Furumoto S,Yoshikawa T,Ishikawa Y,Shibuya K,Okamura N,Iwata R,Yanai K

    更新日期:2012-01-01 00:00:00

  • In vitro evaluation, biodistribution and scintigraphic imaging in mice of radiolabeled anthrax toxins.

    abstract:INTRODUCTION:There is a lot of interest towards creating therapies and vaccines for Bacillus anthracis, a bacterium which causes anthrax in humans and which spores can be made into potent biological weapons. Systemic injection of lethal factor (LF), edema factor (EF) and protective antigen (PA) in mice produces toxicit...

    journal_title:Nuclear medicine and biology

    pub_type: 杂志文章

    doi:10.1016/j.nucmedbio.2008.07.001

    authors: Dadachova E,Rivera J,Revskaya E,Nakouzi A,Cahill SM,Blumenstein M,Xiao H,Rykunov D,Casadevall A

    更新日期:2008-10-01 00:00:00

  • Investigation of four (99m)Tc-labeled bacteriophages for infection-specific imaging.

    abstract:INTRODUCTION:This study investigated radiolabeled bacteriophages for specific detection of infection through gamma imaging. Previously, a (99m)Tc-labeled M13 phage demonstrated specific binding for its host Escherichia coli in vitro and in mice through imaging. METHODS:This study was extended to phages P22, E79, VD-13...

    journal_title:Nuclear medicine and biology

    pub_type: 杂志文章

    doi:10.1016/j.nucmedbio.2008.02.011

    authors: Rusckowski M,Gupta S,Liu G,Dou S,Hnatowich DJ

    更新日期:2008-05-01 00:00:00

  • A new nucleophilic fluorine-18 labeling method for aliphatic mesylates: reaction in ionic liquids shows tolerance for water.

    abstract::[see text for equation] Nucleophilic [(18)F]fluorination of some halo- and mesyloxyalkanes to the corresponding [(18)F]fluoroalkanes with fluoride-18 obtained from an (18)O(p,n) [(18)F]F reaction, using an ionic liquid as a reaction medium, has been studied as a new method for fluorine-18 labeling. Of the various ioni...

    journal_title:Nuclear medicine and biology

    pub_type: 杂志文章

    doi:10.1016/s0969-8051(03)00017-9

    authors: Kim DW,Choe YS,Chi DY

    更新日期:2003-05-01 00:00:00

  • Radiolabelling and PET brain imaging of the α₁-adrenoceptor antagonist Lu AE43936.

    abstract::Cerebral α₁-adrenoceptors are a common target for many antipsychotic drugs. Thus, access to positron emission tomography (PET) brain imaging of α₁-adrenoceptors could make important contributions to the understanding of psychotic disorders as well as to the pharmacokinetics and occupancy of drugs targeting the α₁-adre...

    journal_title:Nuclear medicine and biology

    pub_type: 杂志文章

    doi:10.1016/j.nucmedbio.2012.09.010

    authors: Risgaard R,Ettrup A,Balle T,Dyssegaard A,Hansen HD,Lehel S,Madsen J,Pedersen H,Püschl A,Badolo L,Bang-Andersen B,Knudsen GM,Kristensen JL

    更新日期:2013-01-01 00:00:00

  • [18F]Fluoro-azomycin-2´-deoxy-β-d-ribofuranoside - A new imaging agent for tumor hypoxia in comparison with [18F]FAZA.

    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

    authors: Schweifer A,Maier F,Ehrlichmann W,Lamparter D,Kneilling M,Pichler BJ,Hammerschmidt F,Reischl G

    更新日期:2016-12-01 00:00:00

  • Synthesis and in vivo evaluation of [(11)C]CGP62349, a new GABA(B) receptor antagonist.

    abstract::This paper describes the radiosynthesis of [(11)C]CGP62349, a potential ligand to assess GABA(B) receptors in vivo. (11)C was introduced by O-methylation of the corresponding des-methyl precursor, namely CGP67780. The final product was obtained with a reliable method in good yield. The radioligand was tested in monkey...

    journal_title:Nuclear medicine and biology

    pub_type: 杂志文章

    doi:10.1016/s0969-8051(00)00124-4

    authors: Todde S,Moresco RM,Fröstl W,Stampf P,Matarrese M,Carpinelli A,Magni F,Galli Kienle M,Fazio F

    更新日期:2000-08-01 00:00:00

  • Evaluation of nitrogen-rich macrocyclic ligands for the chelation of therapeutic bismuth radioisotopes.

    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

    authors: Wilson JJ,Ferrier M,Radchenko V,Maassen JR,Engle JW,Batista ER,Martin RL,Nortier FM,Fassbender ME,John KD,Birnbaum ER

    更新日期:2015-05-01 00:00:00

  • Synthesis of an I-123 analog of A-85380 and preliminary SPECT imaging of nicotinic receptors in baboon.

    abstract::A radiosynthetic method to prepare the nicotinic acetylcholine receptor radioligand (S)-5-[123I]iodo-3-(2-azetidinylmethoxy)pyridine, 5-IA, has been developed. The two-step sequence produced [123I]-5-IA in high radiochemical yield (52%), high radiochemical purity (98%), and high specific radioactivities (> 8,500 mCi/m...

    journal_title:Nuclear medicine and biology

    pub_type: 杂志文章

    doi:10.1016/s0969-8051(98)00101-2

    authors: Musachio JL,Villemagne VL,Scheffel UA,Dannals RF,Dogan AS,Yokoi F,Wong DF

    更新日期:1999-02-01 00:00:00

  • PET evaluation of the uptake of N-[11C]methyl CP-643,051, an NK1 receptor antagonist, in the living porcine brain.

    abstract::Antagonists of neurokinin receptors such as CP-643,051 are presently under investigation as potential antidepressants, but little is known about the brain uptake and distribution of these agents. We developed a method for the efficient N-[11C]methylation of CP-122,721, yielding the NK1 antagonist N-[11C]methyl CP-643,...

    journal_title:Nuclear medicine and biology

    pub_type: 杂志文章

    doi:10.1016/j.nucmedbio.2004.03.005

    authors: Bender D,Olsen AK,Marthi MK,Smith DF,Cumming P

    更新日期:2004-08-01 00:00:00

  • Inhibition of serotonin transport by (+)McN5652 is noncompetitive.

    abstract:INTRODUCTION:Imaging of the serotonergic innervation of the brain using positron emission tomography (PET) with the serotonin transporter (SERT) ligand [11C] (+)McN5652 might be affected by serotonin in the synaptic cleft if there is relevant interaction between [11C] (+)McN5652 and serotonin at the SERT. The aim of th...

    journal_title:Nuclear medicine and biology

    pub_type: 杂志文章

    doi:10.1016/j.nucmedbio.2005.12.009

    authors: Hummerich R,Schulze O,Rädler T,Mikecz P,Reimold M,Brenner W,Clausen M,Schloss P,Buchert R

    更新日期:2006-04-01 00:00:00

  • Evaluation of [18F]FDG/[18F]FLT/[18F]FMISO-based micro-positron emission tomography in detection of liver metastasis in human colorectal cancer.

    abstract:INTRODUCTION:Positron emission tomography (PET) is extensively used in clinical oncology for tumor detection. This study aimed to explore the application of the radiotracers [18F]fluorodeoxyglucose ([18F]FDG), 3'-deoxy-3'- [18F]fluorothymidine ([18F]FLT), and [18F]fluoromisonidazole ([18F]FMISO) in the diagnosis and mo...

    journal_title:Nuclear medicine and biology

    pub_type: 杂志文章

    doi:10.1016/j.nucmedbio.2019.07.004

    authors: Jiang H,Zhang R,Jiang H,Zhang M,Guo W,Feng G,Pan W,Xu H,Wang S

    更新日期:2019-01-01 00:00:00

  • 18F-labeled FECNT: a selective radioligand for PET imaging of brain dopamine transporters.

    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

    authors: Goodman MM,Kilts CD,Keil R,Shi B,Martarello L,Xing D,Votaw J,Ely TD,Lambert P,Owens MJ,Camp VM,Malveaux E,Hoffman JM

    更新日期:2000-01-01 00:00:00

  • Specific in vivo binding in the rat brain of [18F]RP 62203: a selective 5-HT2A receptor radioligand for positron emission tomography.

    abstract::In vivo pharmacokinetic and brain binding characteristics of [18F]RP 62203, a selective high-affinity serotonergic 5-HT2A receptor antagonist, were assessed in the rat following intravenous injection of trace amount of the radioligand. The radioactive distribution profile observed in the brain 60 min after injection w...

    journal_title:Nuclear medicine and biology

    pub_type: 杂志文章

    doi:10.1016/0969-8051(95)02008-x

    authors: Besret L,Dauphin F,Huard C,Lasne MC,Vivet R,Mickala P,Barbelivien A,Baron JC

    更新日期:1996-02-01 00:00:00

  • Measuring tumor blood flow with H(2)(15)O: practical considerations.

    abstract::The ability to measure blood flow to tumors non-invasively may be of importance in monitoring tumor therapies, assessing drug delivery, and understanding tumor physiology. Of all the radiotracer methods that have been proposed to measure tumor blood flow, the method based on labeled water-H(2)(15)O-may be the most app...

    journal_title:Nuclear medicine and biology

    pub_type: 杂志文章,评审

    doi:10.1016/s0969-8051(00)00136-0

    authors: Bacharach SL,Libutti SK,Carrasquillo JA

    更新日期:2000-10-01 00:00:00

  • An automated [15Q]H2O production and injection system for PET imaging.

    abstract::A computer controlled [15O]H2O injection system has been designed for multiple bolus injections during PET cerebral blood flow studies. The system is housed in a lead safe, and radiation exposure to nearby personnel is low; we have measured rates of approx. 100 microSv/h (10 mR/h) during 2 min of [15O]H2O production a...

    journal_title:Nuclear medicine and biology

    pub_type: 杂志文章

    doi:10.1016/0969-8051(94)00085-x

    authors: Palmer BM,Sajjad M,Rottenberg DA

    更新日期:1995-02-01 00:00:00

  • Kinetic parameters of 3-[(123)I]iodo-L-alpha-methyl tyrosine ([(123)I]IMT) transport in human GOS3 glioma cells.

    abstract::The radiolabelled amino acid 3-[(123)I]iodo-L-alpha-methyl tyrosine ([(123)I]IMT) is a promising tool for the diagnosis and monitoring of brain tumors using single-photon emission tomography (SPECT). However, little is known about the precise kinetics of [(123)I]IMT uptake in human glioma cells. The kinetic analysis o...

    journal_title:Nuclear medicine and biology

    pub_type: 杂志文章

    doi:10.1016/s0969-8051(01)00191-3

    authors: Riemann B,Kopka K,Stögbauer F,Halfter H,Ketteler S,Phan TQ,Franzius C,Weckesser M,Ringelstein EB,Schober O

    更新日期:2001-04-01 00:00:00

  • Synthesis and evaluation of [123I]-iodo-PK11195 for mapping peripheral-type benzodiazepine receptors (omega 3) in heart.

    abstract::An iodinated analog of PK11195, 1-(2-chlorophenyl)-N-methyl-N-(1-methylpropyl)isoquinoline-3-carboxamide , a specific antagonist of the peripheral-type benzodiazepine receptor (omega 3), has been synthesized in three steps with an overall chemical yield of 40%. Both [123I]- and [125I]-Iodo-PK11195 have been synthesize...

    journal_title:Nuclear medicine and biology

    pub_type: 杂志文章

    doi:10.1016/0969-8051(95)02007-1

    authors: Gildersleeve DL,Van Dort ME,Johnson JW,Sherman PS,Wieland DM

    更新日期:1996-01-01 00:00:00

  • Modulation of organ uptake of 11C-labelled L-DOPA.

    abstract::The present study was undertaken to investigate if pretreatment with pharmacological agents could change the organ uptake of 11C-labelled L-DOPA, and especially if the urinary excretion could be decreased. L-[beta-11C]DOPA was injected IV into unanesthetized Sprague-Dawley rats. After 20 min the rats were decapitated ...

    journal_title:Nuclear medicine and biology

    pub_type: 杂志文章

    doi:10.1016/s0969-8051(96)00149-7

    authors: Bergström M,Lu L,Marquez M,Fasth KJ,Bjurling P,Watanabe Y,Eriksson B,Långström B

    更新日期:1997-01-01 00:00:00

  • Evaluation of (111)In-labeled macrocyclic chelator-amino acid derivatives for cancer imaging.

    abstract:PURPOSE:We evaluated new (111)In-labeled amino acid derivatives, in which the amino acids are conjugated with1,4,7,10-tetra-azacyclododecane-1,4,7,10-tetraacetic acid (DOTA), 1,4,7,10-tetraazacyclododecane-1,7-diacetic acid (DO2A) or 1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid (DO3A). METHODS:DOTA-aminoalanine...

    journal_title:Nuclear medicine and biology

    pub_type: 杂志文章

    doi:10.1016/j.nucmedbio.2011.09.010

    authors: Lee JJ,Shetty D,Lee YS,Kim SE,Kim YJ,Hong MK,Son JY,Jeong JM

    更新日期:2012-04-01 00:00:00

  • A simplified method for the measurement of nonmetabolized 2-[18F]F-A-85380 in blood plasma using solid-phase extraction.

    abstract::Quantification of alpha(4)beta(2)* nicotinic acetylcholine receptors using 2-[(18)F]fluoro-3-(2(S)-azetidinylmethoxy)pyridine (2-[(18)F]FA) and positron emission tomography (PET) imaging requires measurement of nonmetabolized radioligand in blood plasma, which was previously accomplished using high-performance liquid ...

    journal_title:Nuclear medicine and biology

    pub_type: 杂志文章

    doi:10.1016/j.nucmedbio.2006.12.001

    authors: Shumway DA,Pavlova OA,Mukhin AG

    更新日期:2007-02-01 00:00:00

  • Solid phase labeling of monoclonal antibodies with 99mTc using two bifunctional photocleavable reagents.

    abstract::Two photolabile heterobifunctional O-nitrobenzyl reagents were used to modify B72.3 monoclonal antibody followed by immobilization on a solid support. Antibody was labeled with 99mTc and then cleaved from the resin on irradiation with light of peak intensity at 365 nm. The antibody was restored unmodified after cleava...

    journal_title:Nuclear medicine and biology

    pub_type: 杂志文章

    doi:10.1016/0969-8051(94)00147-c

    authors: Ranadive GN,Bloomer WD

    更新日期:1995-07-01 00:00:00

  • Preclinical and clinical evaluation of O-[11C]methyl-L-tyrosine for tumor imaging by positron emission tomography.

    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

    authors: Ishiwata K,Tsukada H,Kubota K,Nariai T,Harada N,Kawamura K,Kimura Y,Oda K,Iwata R,Ishii K

    更新日期:2005-04-01 00:00:00

  • Chemical design of a radiolabeled gelatinase inhibitor peptide for the imaging of gelatinase activity in tumors.

    abstract::Since elevated levels of gelatinases [matrix metalloproteinase (MMP)-2 and MMP-9] are associated with a poor prognosis in cancer patients, these enzymes are potential targets for tumor imaging. In the present study, a cyclic decapeptide, cCTTHWGFTLC (CTT), was selected as a mother compound because of its selective inh...

    journal_title:Nuclear medicine and biology

    pub_type: 杂志文章

    doi:10.1016/j.nucmedbio.2007.04.002

    authors: Hanaoka H,Mukai T,Habashita S,Asano D,Ogawa K,Kuroda Y,Akizawa H,Iida Y,Endo K,Saga T,Saji H

    更新日期:2007-07-01 00:00:00

  • Cellular studies of binding, internalization and retention of a radiolabeled EGFR-binding affibody molecule.

    abstract:INTRODUCTION:The cellular binding and processing of an epidermal growth factor receptor (EGFR) targeting affibody molecule, (Z(EGFR:955))(2), was studied. This new and small molecule is aimed for applications in nuclear medicine. The natural ligand epidermal growth factor (EGF) and the antibody cetuximab were studied f...

    journal_title:Nuclear medicine and biology

    pub_type: 杂志文章

    doi:10.1016/j.nucmedbio.2007.05.010

    authors: Nordberg E,Friedman M,Göstring L,Adams GP,Brismar H,Nilsson FY,Ståhl S,Glimelius B,Carlsson J

    更新日期:2007-08-01 00:00:00

  • A single-injection, two-sample method for measuring renal 99mTc-MAG3 clearance in both children and adults.

    abstract::We present a method for estimating 99mTc-MAG3 clearance from both a single injection and two blood samples that is valid for both adults and children. It was obtained by fitting a scaled two-compartment model (having only two adjustable parameters) to adult and pediatric data from multiple centers. ...

    journal_title:Nuclear medicine and biology

    pub_type: 杂志文章

    doi:10.1016/0969-8051(94)00076-v

    authors: Russell CD,Taylor AT Jr,Dubovsky EV,Eshima D

    更新日期:1995-01-01 00:00:00

  • In vitro uptake and metabolism of [14C]acetate in rabbit atherosclerotic arteries: biological basis for atherosclerosis imaging with [11C]acetate.

    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

    authors: Yamasaki K,Yamashita A,Zhao Y,Shimizu Y,Nishii R,Kawai K,Tamaki N,Zhao S,Asada Y,Kuge Y

    更新日期:2018-01-01 00:00:00

  • PET imaging of TSPO in a rat model of local neuroinflammation induced by intracerebral injection of lipopolysaccharide.

    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

    authors: Ory D,Planas A,Dresselaers T,Gsell W,Postnov A,Celen S,Casteels C,Himmelreich U,Debyser Z,Van Laere K,Verbruggen A,Bormans G

    更新日期:2015-10-01 00:00:00

  • A new 99mTc-complex with a germanium-hydrazide (GeTH) ligand.

    abstract::A new tetrahydrazido-germanium (GeTH) ligand was synthesized, characterized and complexed with 99mTc. The negatively charged 99mTc-chelate was shown to form in high yields at neutral pH in the absence of other reducing agents and exhibits high in vitro and in vivo stability. ...

    journal_title:Nuclear medicine and biology

    pub_type: 杂志文章

    doi:10.1016/0969-8051(94)90184-8

    authors: Singh PR,Katti KK,Katti KV,Corlija M,Ketring AR,Volkert WA,Holmes RR

    更新日期:1994-11-01 00:00:00

  • Radio-copper-labeled Cu-ATSM: an indicator of quiescent but clonogenic cells under mild hypoxia in a Lewis lung carcinoma model.

    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

    authors: Oh M,Tanaka T,Kobayashi M,Furukawa T,Mori T,Kudo T,Fujieda S,Fujibayashi Y

    更新日期:2009-05-01 00:00:00