Partonic flow and $phi$-meson production in Au+Au collisions at $sqrt{s_{NN}}$ = 200 GeV

Phase diagram and electrical properties of Pb(Yb1/2Nb1/2)O3–Pb(Mg1/3Nb2/3)O3–PbTiO3ternary ceramicsChao He,Xiuzhi Li,Zujian Wang,Ying Liu,Dongquan Shen,Tao Li,Xifa Long*Key Laboratory of Optoelectronic Materials Chemistry and Physics,Fujian Institute of Research on the Structure of Matter,Chinese Academy of Sciences,Fujian,Fuzhou350002,China1.IntroductionRelaxor-based complex perovskite ferroelectric materialsPb(B1,B2)O3–PbTiO3(B1=Mg2+,Zn2+,Sc3+,In3+,Yb3+,...,B2=Nb5+,Ta5+,W6+,...)with morphotropic phase boundary(MPB)are widely studied due to excellent dielectric andpiezoelectric properties[1–4].The anomalously high piezoelec-tric properties near the MPB compositions result from largenumber of polarization directions available[5]and the instabilityof the polarization[6–8].Moreover,a new phase of monoclinic hasbeen discovered near MPB region,which contribute to highpiezoelectricity[9–12].This kind of excellent piezoelectricproperties make them promising candidates for the applicationsas high-performance solid state actuators,multilayer ceramiccapacitors,ultrasonic imaging probes and electromechanicaltransducers[1,5,13–16].Therefore,the preparation,electricalproperties,applications and physics of relaxor-based ferroelectricmaterials near the MPB regions have been become hot topics inrecent years.As a typical representative of the relaxor-based ferroelectricmaterials,(1Àx)Pb(Mg1/3Nb2/3)O3–x PbTiO3(PMNT)possessesexcellent piezoelectric performance,the MPB region of whichhas been found in the vicinity of30–35mol%PT[4,17].Forexample,the composition of PMNT(67/33)ceramics exhibit a largepiezoelectric constant of d33=640pC/N and relatively highelectromechanical coupling factors of k p=61%,k t=43%[18].Although PMNT ceramics exhibit superior dielectric and piezo-electric performance,the Curie temperature T C and rhombohe-dral–tetragonal phase transition temperature T RT are quite low,which restricts the application temperature range[4,15].Attemptshave been made to develop new systems with relatively high T Cand high piezoelectricity[19–21].In view of this consideration,the(1ÀxÀy)Pb(Yb1/2Nb1/2)O3–x Pb(Mg1/3Nb2/3)O3–y PbTiO3(PYN–PMN–PT)ternary system appears to be promising materials forhigh temperature applications.Pb(Yb1/2Nb1/2)O3(PYN)wasdiscovered as an anti-ferroelectric material with T C around3028C,which takes on orthorhombic perovskite structure belowT C[22].Similar to the PMN,it can be formed a solid solution withnormal ferroelectric PT to present an MPB region in the vicinity of49–50mol%PT[23,24].Within the MPB,the PYNT(50/50)ceramics have a relative high Curie temperature T C(about3718C)and the piezoelectric constants d33are in the range of175–500pC/N based on different synthetic methods and annealingconditions[25].Furthermore,PYNT ceramics have a relatively lowsintered temperature[25].It is reasonable to expect that PYNT canform a solid solution with PMNT,in which an MPB is expected toexist,and the piezoelectric properties and T C of the MPBcomposition would be enhanced because of high piezoelectricMaterials Research Bulletin48(2013)131–136A R T I C L E I N F OArticle history:Received20January2012Received in revised form6September2012Accepted10October2012Available online18October2012Keywords:A.CeramicsC.X-ray diffractionD.Dielectric propertiesD.FerroelectricityD.PiezoelectricityA B S T R A C TThe ternary ferroelectric ceramics Pb(Yb1/2Nb1/2)O3–Pb(Mg1/3Nb2/3)O3–PbTiO3(PYN–PMN–PT),in thevicinity of morphotropic phase boundary(MPB)region,have been prepared by a two-step syntheticprocess.The ternary phase diagram at room temperature has been established based on the XRD dataanalysis,which exhibits a curved MPB region.The dielectric,ferroelectric and piezoelectric propertieshave been characterized,indicating the electrical properties can be adjusted regularly by choosingcompositions.The Curie temperature T C of ternary system varied from165to3708C.With the increase ofPMN content,the piezoelectric coefficients d33increase from373to505pC/N,and the coercivefield E cdecrease from18to6kV/cm.The results show that the PYN–PMN–PT ternary system can be a potentialmaterial for high temperature applications.ß2012Elsevier Ltd.All rights reserved.*Corresponding author.Tel.:+8659183710369;fax:+8659183710369.E-mail address:lxf@(X.Long).Contents lists available at SciVerse ScienceDirectMaterials Research Bulletinj o u rn a l h om e p a ge:w w w.e l s e v i e r.c o m/l o c a t e/m a t r e s b u0025-5408/$–see front matterß2012Elsevier Ltd.All rights reserved./10.1016/j.materresbull.2012.10.019performance for PMNT and PYNT ceramics and high T C for PYNT at MPB compositions.Based on this consideration,the PYN–PMN–PT ternary crystals have been successfully grown by the top-seeded solution method in our group.The Curie tempera-ture T C,piezoelectric coefficient d33and longitudinal electrome-chanical coupling factor k33at room temperature reach2058C, 1800pC/N and90%,respectively,suggesting excellent piezo-electric properties[26].Therefore,it’s necessary to study the PYN–PMN–PT ternary ceramics system in detail including MPB region and electrical properties so as to provide enough information for the growth of PYN–PMN–PT single crystals with higher piezoelectric properties and higher Curie tempera-ture.In this work,the MPB region of the PYN–PMN–PT ternary system has been determined and the electrical properties have been characterized.2.Experimental procedureThe ceramics of(1ÀxÀy)PYN–x PMN–y PT with the composi-tions of x=0,y=0.49;x=0.15,y=0.39,0.41,0.43,0.45,0.47; x=0.35,y=0.34,0.36,0.38,0.40,0.42;x=0.55,y=0.31,0.33, 0.35,0.37,0.39and x=0.67,y=0were prepared by a two-step synthetic process using PbO,MgO,Nb2O5,Yb2O3,TiO2with high purity(99.9%)as starting materials.First,the precursors of B-siteions were synthesized by columbite or wolframite methods [3,24,27].The columbite precursor MgNb2O6(MN)was prepared at11008C for4h with excess10mol%MgO to suppress pyrochlore phase.The wolframite precursor YbNbO4(YN)was prepared at12008C for4h in stoichiometric proportions.Second, MN,YN,PbO,TiO2were mixed and calcined at8008C for4h with excess3mol%PbO(to compensate the volatilization of PbO)to form PYN–PMN–PT powders.Third,the calcined powders were thoroughly grinding with2wt%polyvinyl alcohol(PVA)as a binder.And then the powders were pressed into pellets,which were heated at6008C for2h to eliminate the binder.The formed pellets were sintered at various temperatures from10408C to 11608C for2h in a sealed Al2O3crucible to form the series of desired ceramics.For structural analysis,X-ray diffraction(XRD)was performed at room temperature on an X-ray diffractometer(Rigaku,Japan) equipped with Cu K a radiation and a graphite monochromator with an angular range of10–808.The data were collected with a scan step of0.028(2u)using a scanning rate of0.58minÀ1.The theoretical density of the sintered samples was calculated based on XRD,while the actual density was measured using Archimedes method.The morphologies of the sintered samples were deter-mined using scanning electron microscopy(SEM,JSM6700,Japan). The obtained samples were polished and coated with silver paste for electrical measurements.The dielectric properties were measured using a computer-controlled Alpha-A broadband dielectric/impedance spectrometer(Novocontrol GmbH),with an AC signal of 1.0V(peak-to-peak)applied.The ferroelectric hysteresis loops were displayed using an aix-ACCT TF2000 analyzer(at f=2Hz)at room temperature.Poling was performed at1208C for15min at a DC electricfield of15–30kV/cm. Piezoelectric coefficient was measured using a quasistatic d33 meter(Institute of Acoustics,Chinese Academy of Sciences,model ZJ-4AN).3.Results and discussionThe XRD patterns of the selected x=0.35series are presented in Fig.1.All the samples exhibit a pure perovskite structure with no secondary phase,indicating that the perovskite structure of the PYN–PMN–PT ceramics is quite stable.Interestingly,it seems that the structure of ceramics samples transfer gradually from rhombohedral to tetragonal phase occurs with increasing PT content.In order to identify the phase compositions between rhombohedral and tetragonal phases,the special attention was focused on(200)reflections around2u=458.Fig.2 presents the experimental XRD data of(200)reflection peaks profiles for some selected samples,which were deconvoluted with the tetragonal and/or rhombohedral phase components.In general,the XRD profiles of(200)reflections will show only a single peak R(200)for the rhombohedral phase due to all the planes of(200)share the same lattice parameters,whereas it splits into two peaks for the tetragonal phase,the T(200)/(020) and T(002)profiles with an intensity ratio of the T(200)/(020) and T(002)peaks of2:1.Therefore,the(200)reflections within the MPB region should be composed of three peaks:one for rhombohedral phase and two for tetragonal phase.As shown in Fig.2,for each series,strong splitting of(200)reflections from rhombohedral to tetragonal phase with PT content increasing. Therefore,there is a region,in each series of x,at which the rhombohedral phase and tetragonal phase co-exist,i.e.,within MPB region.Based on the above analysis,the MPB are found to be located between0.42YN–0.15PMN–0.43PT and0.40PYN–0.15PMN–0.45PT for x=0.15series;between0.27YN–0.35PMN–0.38PT and0.25YN–0.35PMN–0.40PT for x=0.35series;be-tween0.10YN–0.55PMN–0.35PT and0.08YN–0.55PMN–0.37PT for x=0.55series at room temperature respectively.Thus,the ternary phase diagram of PYN–PMN–PT solid solution at room temperature has been established as shown in Fig.3,including the reported MPBs for PMNT and PYNT binary system,being30–35mol%PT and49–50mol%PT[4,17,23,24].It can be seen that the ternary MPB region is a curved region rather than a linear region.The results are consistent with the result of previous studies[28].SEM micrographs of the surface for the compositions within the MPB region are shown in Fig.4.It is clearly can be seen that few pore in the obtained ceramics.The grain size of above samples was listed in Table1.It is found that with increasing PYN content,the grain size of PYN–PMN–PT within the MPB region change irregularly.The theoretical and actual density of the samples was presented in Table1. The relative density,listed in Table1,indicates relative highdense.Fig.1.X-ray powder diffraction patterns of(1ÀxÀy)PYN–x PMN–y PT ceramics for the selected series:x=0.35,indicating a phase transition from the rhombohedral to tetragonal phase upon increasing PT.C.He et al./Materials Research Bulletin48(2013)131–136 132Fig.5shows the temperature dependences of the real (e 0)and loss (tan d )parts of dielectric permittivity measured at 1–100kHz for selected sample (0.27PYN–0.35PMN–0.38PT).It can be seen that the Curie temperature T C is about 2508C.The dielectric constant shows a broad maximum with frequency dispersion,the temperature of which (T max )shifts to higher temperatures with increasing frequency,indicating a typical relaxor behavior.Apart from the T C ,another anomaly is found at around 1208C,corresponding to rhombohedral–tetragonal transition temperature (T RT ).It suggests that 0.27PYN–0.35PMN–0.38PT ceramics is within the MPB region,which isconsistent with the analysis of XRD patterns.At room tempera-ture,the e 0and tan d for 0.27PYN–0.35PMN–0.38PT ceramics are 1570and 0.0243respectively.The value of tan d increases significantly at the temperature above higher than T C due to the higher conductivity at high temperature.Fig.6(a)presents the T C and T RT for ceramics along the MPB region as a function of x (PMN).It can be seen that the T C and T RT can vary in a quite large range with increasing PMN content,which provide possibility for us to choose different compositions to meet the different applicable requirement.Fig.6(b)depicts piezoelec-tric coefficients d 33of ternary PYN–PMN–PT ceramics asaFig.2.Pseuocubic (200)reflections of (1Àx Ày )PYN–x PMN–y PT ceramics for the selected series:(a)x =0.15;(b)x =0.35;(c)x =0.55,which were fitted by the Gaussian functions (peaks 1and 2representing the tetragonal phase and peak 3corresponding to the rhombohedral phase).C.He et al./Materials Research Bulletin 48(2013)131–136133function of x (PMN)content in the vicinity of the MPB region.The d 33increase from 373to 505pC/N with PMN increasing.It is shown that ternary PYN–PMN–PT ceramics exhibit high piezo-electricperformance.Fig. 3.The ternary MPB phase diagram of (1Àx Ày )PYN–x PMN–y PT at room temperature and sampleslocations.Fig.4.SEM micrographs of the surface for selected PYN–PMN–PT ceramics within the MPB region.Table 1Theoretical density (r T ),actual density (r A ),relative density (r R )and grain size (G )of selected compositions within the MPB region.Compositionsr T(g/cm 3)r A(g/cm 3)r R(%)G (m m)0.67PMN–0.33PT8.217.8895.982–80.10PYN–0.55PMN–0.35PT 8.247.8395.021–40.27PYN–0.35PMN–0.38PT 8.317.9896.031–50.42PYN–0.15PMN–0.43PT 8.417.9594.532–80.51PYN–0.49PT8.578.2396.032–10C.He et al./Materials Research Bulletin 48(2013)131–136134Fig.7displays the ferroelectric hysteresis loops for selected samples.All samples exhibit saturated loops at an electric field Æ20–40kV/cm.The coercive field E c and remanent polarization P r varies with different PMN content.Among them,the remnant polarizations for 0.67PMN–0.33PT and 0.51PYN–0.49PT ceramics are 29.2m C/cm 2and 36.3m C/cm 2respectively.It is worth noting that the E c values vary from 18to 6kV/cm with PMN content increasing,which indicates the stability for poled samples can be controlled by the compositions.4.Conclusions(1Àx Ày )PYN–x PMN–y PT ceramics were prepared by two-step method and characterized by dielectric,ferroelectric and piezoelectric measurements.The phase diagram of ternary system at room temperature has been established based on the XRD analysis,indicating the MPB region is a curved region,instead of a linear region.Upon increasing PMN content,the E c ,T C and d 33vary pared with PMNT ceramics,the electrical properties can be adjusted in the larger range regularly,for example,the T C can be adjusted in the range 165–3708C with different compositions,and the d 33varies in the range of 373–505pC/N,which is beneficial for potential electromechanical applications.AcknowledgmentsThis work was supported by the National Natural Science Foundation of China under Grant No.91122020and the Fund of Key Projects of Fujian Provincial (2010H0023).References[1]L.E.Cross,Ferroelectrics 76(1987)241–267.[2]G.H.Haertling,J.Am.Ceram.Soc.82(1999)797–818.[3]S.W.Choi,T.R.Shrout,S.J.Jang,A.S.Bhalla,Ferroelectrics 100(1989)29–38.[4]Q.Lu,X.Long,Y.Hu,CrystEngComm 12(2010)4317–4320.[5]S.E.Park,T.R.Shrout,J.Appl.Phys.82(1997)1804–1811.[6]M.Ahart,M.Somayazulu,R.E.Cohen,P.Ganesh,P.Dera,H.k.Mao,R.J.Hemley,Y.Ren,P.Liermann,Z.Wu,Nature 451(2008)545–549.[7]B.Noheda,D.E.Cox,G.Shirane,S.E.Park,L.E.Cross,Z.Zhong,Phys.Rev.Lett.86(2001)3891–3894.[8]H.Fu,R.E.Cohen,Nature 403(2000)281–283.[9]B.Noheda, D.E.Cox,G.Shirane,J.Gao,Z.G.Ye,Phys.Rev.B 66(2002)054104.[10]-Orauttapong,B.Noheda,Z.G.Ye,P.M.Gehring,J.Toulouse,D.E.Cox,G.Shirane,Phys.Rev.B 65(2002)144101.[11]J.M.Kiat,Y.Uesu,B.Dkhil,M.Matsuda,C.Malibert,G.Calvarin,Phys.Rev.B 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[4] Corrosion on Plasma Etched Metal Lithography from Processing and Environmental Factors. K.E.Mautts, Electrochemical Society Proceedings, Vol. 97-31, page 240, 1997. [5] Characterization of Metal Pattern Density and Metal Stack Composition on Chlorine Residues from Metal Etch Process. S. Y. Loong et al, SPIE Conference on Multilevel Interconnect T[6e]cPhrneovleongtyio, nVolf. C35o0rr8o,sSioannDtaaCmlagrae, ACfafelicfotirnngiaP. lSaespmteamEbtcehre1d99A8l .Alloy Lithography. G. Gebara et al. Proceedings of the 10th Symposium on Plasma Processing. Dielectric Science and Technology and E[7l]eRcterodnuictiDoniviosfioCno, rVroosl.io9n4-D2e0f,epcatsgeon42M1e,t1a9l 9A4ll.oy Interconnections. G. Gebara and K. Mautz, VMIC Conference, page 326, June 1993.
所以不同的透射率的产品在铝金属蚀刻时，同样的铝金属腐蚀，但是引起腐蚀的原因是不同的。我们 要针分对析低出透正射确率的的成产因品，，并主采要取防相止应的得是措过施量。 侧壁聚合物的生成，可采取的措施有： 1）降低偏置射频功率，从而减少侧壁聚合物的生成。 2) 减少光刻胶的厚度，保证刻蚀后光刻胶残留的条件下，减少侧壁聚合物的生成。 3) 减少CHF3 /CH4等气体的流量，从而减少侧壁聚合物的生成。 4) 减少过蚀刻（Over Etch）时间，从而减少侧壁聚合物的生成,但要保证足够的氧化层损耗。 针对高透射率的产品，主要防止的是侧壁钝化的不足，即增加聚合物的生成，可采取的措施有： 1) 增加光刻胶的厚度，增加侧壁聚合物的生成。 2) 增加CHF3 /CH4等气体的流量，从而增加侧壁聚合物的生成。 3) 增加过蚀刻（Over Etch）时间，增加侧壁聚合物的生成。 结论

细胞培养用青霉素-链霉素产品简介：细胞培养用青霉素-链霉素(Penicillin-Streptomycin for Cell Culture)为粉剂，是最常用的细胞培养用抗生素(即通常所谓的双抗)。

在细胞培养液中推荐的青霉素的工作浓度为100U/ml ，链霉素的工作浓度为0.1mg/ml 。

一个包装的细胞培养用青霉素-链霉素可以配制80L 细胞培养液。

保存条件：室温保存。

4ºC 保存可以使用更长时间。

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使用说明：细胞培养用青霉素-链霉素可以参考如下两种方法之一使用：1. 配制细胞培养液时加入细胞培养用青霉素-链霉素，然后再过滤除菌：配制细胞培养液时按照青霉素的工作浓度为100U/ml ，链霉素的工作浓度为0.1mg/ml 进行配制，配制完成后过滤除菌即可使用。

2. 配制青霉素-链霉素溶液(100X)母液，然后再添加到细胞培养液中：按照青霉素的含量为10KU/ml ，链霉素的含量为10mg/ml ，配制青霉素-链霉素溶液(100X)母液。

过滤除菌后即可按照100倍稀释加入到细胞培养液中使用。

配制的母液可以-20ºC 冻存。

使用本产品的文献：1. Wang PH, Gu ZH, Wan DH, Zhang MY , Weng SP, Yu XQ, He JG. The shrimp NF-κB pathway is activated by white spot syndrome virus (WSSV) 449 to facilitate the expression of WSSV069 (ie1), WSSV303 and WSSV371.PLoS One. 2011;6(9):e24773.2. Xia M, Zhu Y . Signaling pathways of ATP-induced PGE2 release inspinal cord astrocytes are EGFR transactivation-dependent. Glia. 2011 Apr;59(4):664-74. 3. He YH, Song Y , Liao XL, Wang L, Li G, A lima, Li Y , Sun CH. Thecalcium-sensing receptor affects fat accumulation via effects on antilipolytic pathways in adipose tissue of rats fed low-calcium diets. J N utr. 2011 Nov;141(11):1938-46. 4. Liu XY , Wei W, Wang CL, Yue H, Ma D, Zhu C, Ma GH, Du YGApoferritin-camouflaged Pt nanoparticles: surface effects on cellular uptake and cytotoxicity. J. Mater. Chem., 2011,21, 7105-7110. 5. Wang MN, Liu XY , Cao CB, Shi C Synthesis of band-gap tunable Cu –In –S ternary nanocrystals in aqueous solution RSC Adv. 2012 Feb; 7:2666-70. 6. 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British Journal of Haematology ,2001,113,369±374Technetium-99m-sestamethoxyisobutylisonitrile scan as a predictor of chemotherapy response in malignant lymphomas compared with P-glycoprotein expression,multidrug resistance-related protein expression and other prognosis factorsChia-Hung Kao,1Shih-Chuan Tsai,2Jhi-Joung Wang,3Yung-Jen Ho,4Shung-Tai Ho 5and Sheng-Ping Changlai 61Department of Nuclear Medicine,Taichung Veterans General Hospital,Taichung,2Department of Nuclear Medicine,Show-Chwan Memorial Hospital,Chunghua,3Department of Medical Research,Chi-Mei Medical Centre,Tainan,4Department of Radiology,Jen-Ai Hospital,Taichung,5School of Medicine,National Defence Medical Centre,Taipei,and 6Department of Nuclear Medicine,Chung-Shan Medical and Dental Hospital,Taichung,TaiwanReceived 13November 2000;accepted for publication 14January 2001Summary .The purpose of the present study was to predict the response of malignant lymphomas (MLs)to chemotherapy usingtechnetium-99m methoxyisobutylisonitrile (Tc-MIBI)scan and to compare it with the predictive ability of P-glycoprotein (P-gp)expression,multidrug resistance-related protein (MRP)expression and other prognosis factors.Twenty-five ML patients were enrolled in this study prior to initiation of chemotherapy .Images were obtained 10min after intravenous injection of Tc-MIBI,interpreted visually and the tumour-to-background (T/B)ratios calculated.Immunohistochemical analyses were performed on sections of the biopsy specimens to determine P-gp and MRP expression.Chemotherapy response was evaluated in the first 1±2years after completion of chemotherapy .The mean T/B ratio of the 15patients with agood response (3´3^0´6)was significantly higher than that of the 10patients with a poor response (1´2^0´1).All 15patients with a good chemotherapy response had positive Tc-MIBI scan results and negative P-gp and MRPexpression.All 10patients with a poor response had negative Tc-MIBI scan results and either positive P-gp or MRP expression.Other prognosis factors showed no significant difference in the incidence of good and poor responses.Tc-MIBI scan results represent P-gp or MRP expression more accurately than other prognosis factors and predict the chemotherapy response in ML patients.Keywords:malignant lymphoma,technetium-99m methoxy-isobutylisonitrile,chemotherapy response,P-glycoprotein expression,multidrugresistance-related protein expression.Chemotherapy is the primary therapeutic modality for many malignant lymphomas (MLs)including all non-Hodgkin's lymphoma (NHL)cases and many cases of Hodgkin's disease (HD)(Barr et al ,1997;Neal &Hoskin,1997;Wilson &Chabner,1998).As resistance to chemotherapeutic agents is a major cause of treatment failure,the goal of chemotherapy for ML is to avoid possible resistance and achieve the highest response.The mechanism of tumour uptake of technetium-99m methoxyisobutylisonitrile (Tc-MIBI)may involve bindingto the cytosol of the tumour cell (Hassan et al ,1989).The cationic charge and lipophilicity of Tc-MIBI,mitochondrial and plasma membrane potentials of tumour cells,and cellular mitochondrial content can all play a significant role in tumour uptake of this agent (Chiu et al ,1990),or the uptake may be caused by indirect phenomena such as increased tumour blood flow and capillary permeability .Tc-MIBI scans have been used to successfully predict the chemotherapy response of MLs (Kapucu et al ,1997;Shih et al ,1998).However,the previous studies have not compared the relationship between Tc-MIBI scan resultsq 2001Blackwell Science Ltd369Correspondence:Chia-HungKao,MD,Department of Nuclear Medicine,TaichungVeterans General Hospital,160Taichung Harbour Road,Section 3,Taichung407,Taiwan.E-mail:kaoch@ .twand P-glycoprotein(P-gp)or multidrug resistance-related protein(MRP)expression in predictingthe chemotherapy response of MLs.Therefore,the aim of this study was to compare Tc-MIBI scan results,immunohistochemical ana-lyses of P-gp and MRP expression,and other prognosis factors as predictors of chemotherapy response in ML patients.PATIENTS AND METHODSPatients.Twenty-five patients(13men,12women;age range25±65years;mean age:46´2^12´3years)with ML(11with HD and14with NHL)were included in the study and underwent Tc-MIBI scans prior to chemotherapy (Table I).The classification of ML followed the Lukes and Butler and updated Kiel systems(Jaffe,1998).After Tc-MIBI scans,the11HD patients received chemotherapy regimens with nitrogen mustard(mechlorethamine),vincristine, procarbazine and prednisone(MOPP),alternatingwith doxorubicin,bleomycin,vinblastine and dacarbazine (ABVD);the14NHL patients received chemotherapy regimens with cyclophosphamide,doxorubicin,vincristine and prednisone(CHOP)protocols(Barr et al,1997;Neal& Hoskin,1997;Wilson&Chabner,1998).Technetium-99m methoxyisobutylisonitrile scan.The ima-ging procedure began30min after oral intake of500mg of perchlorate to prevent any abnormal uptake of free Tc-99m pertechnetate.A commercial MIBI preparation(max. 5´56GBq in approximately1±3ml)was obtained from The Du Pont Merck Pharmaceutical Company(Cardiolite, Billerica,MA,USA).The labellingand quality control procedures were carried out accordingto the manufac-turer's bellingefficiencies were all.95%. Each patient was place in a supine position on the imaging table with the chest strapped to prevent motion. Because of physiological Tc-MIBI accumulation in abdom-inal and pelvic organs,visualization of MLs located in abdominal and pelvic regions is unreliable.In this study, images of supradiaphragmatic MLs were obtained10min after intravenous injection of740MBq Tc-MIBI in the anterior and posterior projection.The equipment consisted of a large field-of-view gamma camera fitted with a low-energy,high-resolution collimator.A single20%energy window was set at140keV and500K counts were obtained for each static image.Tumour-to-background(T/ B)ratios were calculated as the mean counts over the region of interest(ROI)of the tumour outlined in the largest lesion4the mean counts over the ROI ofTable I.Detailed data of patients in this study.Case Tc-MIBI scan results Immunohistochemical stainingAge BChemotherapyresponsenumber Sex T/B ratio Visual interpretation P-gp expression MRP expression(years)Type Stage symptoms results1Female1´0Negative Positive Negative33HD I Yes Poor2Female1´0Negative Negative Positive53NHL III No Poor3Female1´1Negative Positive Negative40HD II Yes Poor4Male1´1Negative Positive Negative51NHL III No Poor5Male1´1Negative Negative Positive62HD IV No Poor6Male1´2Negative Positive Negative35NHL IV No Poor7Male1´2Negative Negative Positive55HD IV Yes Poor8Female1´3Negative Positive Negative27NHL III Yes Poor9Male1´3Negative Negative Positive65NHL III Yes Poor10Male1´4Negative Positive Negative43NHL II Yes Poor11Female2´4Positive Negative Negative43HD II Yes Good12Male2´7Positive Negative Negative56HD IV No Good13Male2´8Positive Negative Negative37NHL III No Good14Male2´9Positive Negative Negative55HD I Yes Good15Male2´9Positive Negative Negative62HD IV No Good16Male3´0Positive Negative Negative61NHL III No Good17Female3´2Positive Negative Negative31NHL III No Good18Male3´2Positive Negative Negative47HD IV No Good19Female3´3Positive Negative Negative60HD III Yes Good20Male3´3Positive Negative Negative25NHL II Yes Good21Female3´6Positive Negative Negative30HD II Yes Good22Female3´6Positive Negative Negative58NHL IV No Good23Male4´0Positive Negative Negative35HD IV No Good24Female4´1Positive Negative Negative50NHL III No Good25Male4´5Positive Negative Negative42NHL II Yes GoodHD,Hodgkin's disease;NHL,non-Hodgkin's lymphoma;P-gp,P-glycoprotein;MRP,multidrug resistance-related protein;Tc-MIBI, technetium-99m methoxyisobutylisonitrile;T/B,tumour-to-background.370 C.-H.Kao et alq2001Blackwell Science Ltd,British Journal of Haematology113:369±374background,defined as the contralateral normal side for the neck and axilia lesions or normal soft tissue of the thorax for mediastinal lesions.Tc-MIBI uptake in the lesions $axillary soft tissue background,based on the visual interpretation of at least two experienced nuclear medicine physicians,was considered a positive Tc-MIBI scan result (Figs 1and 2).Immunohistochemical staining.Formalin-fixed paraffin sections (5m m)were deparaffinized in an oven at 508C for 40min,then hydrated with varyingconcentrations of ethanol±water dilutions.For MRP immunohistochemical staining,antigen retrieval was performed by treatment in citrate buffer in a 700W microwave oven for 5min.Endogenous peroxidase was blocked by 3%hydrogen peroxide for 15min,followed by 5min in phosphate-buffered saline (PBS).The sections were incubated over-night in a moist chamber at 48C with primary antibody MRP QCRL-1(10m g/ml,Signet Laboratories,Dedham,MA,USA)at 1:100concentration.For P-gp immunohis-tochemical staining,endogenous peroxidase was blocked by 3%hydrogen peroxide for 15min.Antigen retrieval was performed by treatment with enzyme digestion in 0´1%trypsin in PBS for 5min at room temperature and inhibited with 10%skimmed milk in PBS for 5min.The sections were incubated for 2h in a moist chamber at 378C with primary antibody JSB-1(50m g/ml,Boehringer Mannheim Biochemica,Germany)at 1:50concentration.After three 5min washes in PBS,detection of the primary antibody was performed with a link antibody accordingto the manufacturer's instructions (DAKO LSAB_2System,Peroxidase,Dako Corporation,Carpinteria,CA,USA)(Niehans et al ,1992;Marie,1995;Yamaguchi et al ,1995;Kostakoglu et al ,1998;Webb et al ,1998).P-gp and MRP expressions were interpreted by an experienced pathologist blind to clinical outcome as follows:negati-ve less than 10%,positive 10%or more stained tumour cells (Figs 3and 4).Chemotherapy response evaluation.In this study ,the chemotherapy response of each patient was evaluated for the first 1±2years after completion of treatment using clinical and radiological methods such as plain chest X-ray ,chest computerized tomography (CT)or magnetic resonance imaging (MRI),as well as head and neck CT or MRI,accordingto the followingscale:(1)Complete response no evidence of disease,(2)Partial respon-se at least 50%decrease in the sum of the products of the maximum perpendicular diameters of all measurable lesions,no evidence of progression in any lesion and no new lesions,(3)No response less than 25%increase in the sum of the products of the maximum perpendicular diameters of all measurable lesions,no evidence of progression in any lesion and no new lesions,and (4)Progressive disease at least 25%increase in the sum of the products of the maximum perpendicular diameters of all measurable lesions and/or the appearance of new lesions.We defined complete and partial responses as good response,while no response and progressive disease were defined as poor response.Statistical analyses.The T/B ratio was expressed as meanT a b l e I I .D i s t r i b u t i o n s o f T c -M I B I s c a n r e s u l t s ,P -g p e x p r e s s i o n ,M R P e x p r e s s i o n ,a g e ,t u m o u r t y p e ,t u m o u r s t a g e a n d B s y m p t o m s r e l a t e d t o c h e m o t h e r a p y r e s p o n s e r e s u l t s .I m m u n o h i s t o c h e m i c a l s t a i n i n gC h e m o t h e r a p y r e s p o n s e T c -M I B I s c a n r e s u l t s P -g p e x p r e s s i o nM R P e x p r e s s i o nA g e T y p e S t a g eB s y m p t o m sr e s u l t s P o s N e g P -v a l u eP o s N e g P -v a l u e P o s N e g P -v a l u e#40y e a r s .40y e a r s P -v a l u e H D N H L P -v a l u e I ±I I I I I ±I V P -v a l u e Y e s N o P -v a l u e G o o d1500150155107851069P o o r 010,0´0164,0´0146,0´01460´73460´74370´86640´33q 2001Blackwell Science Ltd,British Journal of Haematology 113:369±374Tc-MIBI Predicts Chemotherapy Response in HD and NHL371^standard deviation (SD).A Mann±Whitney U -test was used to evaluate the difference in T/B ratios between patients with a good versus a poor response.The difference in incidence of good and poor response was evaluated for eight possible prognosis factors:positive versus negative Tc-MIBI scan results,positive versus negative P-gp expression,positive versus negative MRP expression,HD versus NHL,stage I±II versus stage III±IV ,age .40years versus #40years,and with B symptoms versus without B symptoms (night sweats,fever .388C for three consecutive days and unexplained weight loss of .10%body weight)(Barr et al ,1997;Neal &Hoskin,1997).A Chi-square test was used to determine if the frequency of good and poor response was the same for each pair.If the P -value was ,0´05,the difference was considered significant.RESULTSDetailed patient data are shown in Table I.The mean T/B ratio of the 15patients with a good response (3´3^0´6)was significantly (P ,0´01)higher than that of the 10patients with a poor response (1´2^0´1).All 15(100%)patients with a good response had positive Tc-MIBI scan results and negative P-gp and MRP expression.All 10(100%)patients with a poor response had negativeTc-MIBI scan results,six (60%)of whom had positive P-gp expression while the other four (40%)had positive MRP expression.Tc-MIBI scan results,P-gp expression and MRP expression all showed significant differences in the rate of good and poor responses.However,no significant difference in the incidences of good and poor responses was found for lymphoma type,stage,age or B symptoms (Table II).DISCUSSIONOur review of previous literature found only one paper that reported that 17ML children with positive Tc-MIBI scan results and a higher mean T/B ratio had a better response to chemotherapy than seven ML children with negative Tc-MIBI scan results and a lower mean T/B ratio (Kapucu et al ,1997).Our results support their findings.However,their study did not examine the relationship between other prognosis factors,P-gp or MRP expression,and chemo-therapy response.The mechanism of chemotherapy resistance in ML is thought to involve expression of P-gp and MRP (Niehans et al ,1992;Yamaguchi et al ,1995;Zhan et al ,1997;Webb et al ,1998).The retention of Tc-MIBI in tumour cells depends on P-gp and MRP expression and they function as ATP-dependent efflux pumps for manychemotherapyFig 1.Case no.25had a goodchemotherapy response result.(A)Tc-MIBI scan reveals significant tracer uptake in the right neck and the result is positive (T/B ratio 4´5)(arrow).(B)Neck computerized tomography shows a mass in the same area(arrow).Fig 2.Case no.4had a poorchemotherapy response result.(A)Tc-MIBI scan reveals no definitely abnormal tracer MIBI uptake in the chest and neck and the result is negative (T/B ratio 1´1).(B)Gallium-67citrate scan shows multiple abnormal tracer uptake in the chest and neck (arrows).372 C.-H.Kao et alq 2001Blackwell Science Ltd,British Journal of Haematology 113:369±374agents (Hendrikse et al ,1998,1999;Vergote et al ,1998;Sun et al ,2000).Therefore,in this study we used the Tc-MIBI scan to predict the response of MLs to chemother-apy .We found that positive Tc-MIBI scan results accurately predicted all good chemotherapy results,which were also related to negative P-gp and MRP expression.Moreover,negative Tc-MIBI scan results accurately predicted poor chemotherapy results in all patients with positive P-gp or MRP expression (Table I).In our previous studies,only early chest images performed 10min after intravenous injection of Tc-MIBI proved to be accurate enough to predict chemotherapy response in lung and breast cancer (Kao et al ,1998,2000;Vergote et al ,1998).Therefore,in this study ,we did not consider it necessary to perform delayed chest imaging to calculate the tumour washout rate or retention index of Tc-MIBI to predict the chemotherapy response.mRNA expression is not fully corrected with P-gp or MRP expression in the tumour cell membrane,Tc-MIBI tumour uptake is directly based onthe P-gp or MRP expression in the tumour cell membrane,and it was impossible to extract mRNA from the formalin-fixed paraffin sections of biopsy specimens (Wang et al ,1997;Dexter et al ,1998;Yokogami et al ,1998).Therefore,we directly detected P-gp or MRP expression using immunostainingto correct with Tc-MIBI tumour uptake (T/B ratio)in our study .Based on our findings,we conclude that Tc-MIBI scan results can represent P-gp and MRP expression for predict-ingthe chemotherapy response in ML 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