原位脑胶质瘤99Tcm-Galacto-RGD2 microSPECT/CT靶向显像研究

目的 合成 ⁹⁹Tc^m-半乳糖化精氨酸-甘氨酸-天冬氨酸多肽(⁹⁹Tc^m-HYNIC-Galacto-RGD₂-tricine-TPPTS, ⁹⁹Tc^m-Galacto-RGD₂),探讨其用于原位胶质瘤靶向显像的价值。方法 一步法制备⁹⁹Tc^m-Galacto-RGD₂,考察其体内外稳定性及体内生物学分布;构建荷人原位脑胶质瘤(U87MG)动物模型,⁹⁹Tc^m-Galacto-RGD₂尾静脉注射后行microSPECT/CT显像,勾画肿瘤感兴趣区,定量肿瘤的放射性摄取,病理学检查肿瘤整合素α_Ⅴβ₃表达水平,与放射性摄取进行相关性分析。结果⁹⁹Tc^m-Galacto-RGD₂放射化学纯度为(97.7±0.8)%,体内外稳定性好,能与脑胶质瘤细胞特异性结合,IC₅₀为(18±3)nmol/L。裸鼠尾静脉注射后血液清除快,脑组织放射性摄取少。静脉注射60 min后,肿瘤放射性摄取明显高于30 min(t=7.13, P<0.05),1 h肿瘤/脑组织放射性摄取比为13.92±3.43。microSPECT-CT显像阻断2 min后,肿瘤放射性摄取显著低于非阻断组(t=11.36,P<0.05);基于microSPECT-CT显像勾画肿瘤感兴趣区获得的肿瘤体积与肿瘤参考体积具有较好的一致性(95%CI=-11.94%~11.92%)。肿瘤⁹⁹Tc^m-Galacto-RGD₂摄取与整合素α_Ⅴβ₃表达水平呈线性相关(R²=0.896)。结论 ⁹⁹Tc^m-Galacto-RGD₂易于合成,理化性质好,microSPECT-CT融合显像可用于脑胶质瘤病灶的感兴趣区勾画和评价肿瘤组织整合素α_Ⅴβ₃的表达水平。     

HER-2受体放射性配体99Tcm-TP1623的制备及其在正常动物体内的分布

目的 探讨HER-2受体放射性配体 ⁹⁹Tc^m-B2-S22-AFA(⁹⁹Tc^m-TP1623)在健康小鼠体内的生物分布和健康家兔体内的动态显像分布.方法 采用氯化亚锡间接法 ⁹⁹Tc^m标记TP1623,3MM色谱纸层析测定 ⁹⁹Tc^m-TP1623标记率,计算其比活度;通过体外稳定性实验、血清蛋白结合实验和油/水分配实验,鉴定标记产品理化性质;研究 ⁹⁹Tc^m-TP1623于1、5、10、30、60和120 min在健康小鼠体内的生物分布特性;通过SPECT显像,结合感兴趣区(ROI)时间-放射性曲线分析,观察 ⁹⁹Tc^m-TP1623在健康家兔体内的动态分布变化.结果 ⁹⁹Tc^m-TP1623标记率为(96.4±0.1)%,比活度为(24.35±0.06)TBq/mmol,室温下放置6 h后放化纯度为(95.03±0.97)%.油/水分配系数P为－(2.51±0.15).小鼠血液放射性清除快,通过肾脏排泄较快,心、肺、肝、肌肉、骨骼等放射性随时间延长逐渐减低,60 min后放射性呈明显低水平,肠道放射性则随时间缓慢增加.脑放射性始终呈最低水平.健康家兔体内 ⁹⁹Tc^m-TP1623血池影消退迅速,主要通过肾脏排泄,见胆囊、肠道排泄影,胃区和颈部未见放射性浓聚,脑组织始终呈低本底.结论 ⁹⁹Tc^m-TP1623制备方法简便,标记率及产品比活度高,体内、外稳定性好,具有优良的动物体内动力学特性.     

~(99)Tc~m-HL91与~(99)Tc~m-MIBI在Lewis肺癌小鼠模型中的实验研究

目的　进行99Tcm 4,9 二氮 3,3,10 ,10 四甲基十二烷 2 ,11 二酮肟 (HL91)和99Tcm 甲氧基异丁基异腈 (MIBI)肿瘤显像对比研究 ,探讨99Tcm HL91诊断肿瘤的可能性。方法　各取 4只移植性Lewis肺癌小鼠分别注射99Tcm HL91或99Tcm MIBI,2、4h后进行全身后位静态显像 ,利用感兴趣区技术 ,分别计算不同时相肿瘤与头 (T/H)、胸 (T/C)、对侧部位 (T/L)的放射性比值。 4h后处死99Tcm HL91显像小鼠 4只 ,取血并剥离脏器及肿瘤组织 ,称重 ,测量放射性计数 ,计算肿瘤与各脏器放射性比值。结果　99Tcm MIBI显像组的肿瘤部位显影均不清晰 ,其中 2和 4h的T/C为 0 2 0± 0 0 8和 0 14± 0 0 7,两时相之间无明显差异。99Tcm HL91显像组各时相肿瘤显影均较清晰 ,其中 2和 4h的T/C为3 2 5± 1 2 5和 2 44± 1 0 7,两时相间无明显差异 ,而与99Tcm MIBI显像组各时相比较差异有显著性 (t=4 8～ 7 5 ,P <0 0 1)。体外测量肿瘤与脑、胸等脏器的单位重量放射性比值较高 ,肿瘤与肝、肾等腹部脏器的单位重量放射性比值较低。结论　在移植性Lewis肺癌小鼠组织中 ,99Tcm MIBI显像效果不佳 ,而99Tcm HL91吸收良好且清除缓慢。     

SPECT/CT同机融合显像检测鼻咽癌侵犯颅底骨的临床价值

目的 探讨⁹⁹Tc^m-亚甲基二膦酸盐（MDP）SPECT结合定位CT对鼻咽癌（NPC）颅底骨侵犯（SBBI）检测能力及临床价值。方法 对165例鼻咽癌初治患者于放疗前同期进行⁹⁹Tc^m-MDP SPECT结合定位CT鼻咽颅底断层骨显像和MRI检查。于SPECT/CT图像矢状面,颅底放射性浓聚程度最高（L）层面与高位颈椎体（C1~C3,S）处勾画相同大小的感兴趣区（ROI）,计算其放射性摄取比值,L/S>1提示SBBI。以MRI结果为标准,采用双盲法对两者检测结果进行比较。根据肿瘤的不同侵犯途径,进一步把颅底骨分斜坡、岩尖、蝶骨体、蝶窦底和翼突、翼板等区域进行统计分析。结果 SPECT/CT检测SBBI总体灵敏度、特异性、准确度、阳性预测值、阴性预测值、к值分别为96.74%（89/92）、72.60%（53/73）、86.06%（142/165）、81.65%（89/109）、94.64%（53/56）、0.711,ROC曲线下面积0.847,差异有统计学意义（Z=12.436,P<0.01）;斜坡、岩尖区域的阳性预测值（91.67%）明显高于蝶骨体、蝶窦底区域和翼突、翼板区域的阳性预测值（30.00%、14.29%）。结论 ⁹⁹Tc^m-MDP SPECT/CT能有效地检测鼻咽癌SBBI,尤其在斜坡、岩尖区域,与MRI检测结果高度一致。     

2017—2020年北京地区大气气溶胶中7 Be和210 Pb放射性活度浓度监测与分析

目的 监测与分析2017—2020年北京地区大气气溶胶中⁷Be和²¹⁰Pb放射性活度浓度变化情况,为有效防治空气污染提供科学依据。方法 利用大流量空气气溶胶采样器（SnowWhite）采集气溶胶样品1 074份,其中春季、夏季、秋季和冬季分别采集275、266、262和271份。使用低本底高纯锗伽马谱仪（ORTEC）分析气溶胶样品中⁷Be和²¹⁰Pb放射性活度浓度。结果 2017—2020年北京地区大气气溶胶中⁷Be放射性活度浓度的变化范围为0.56~14.84 mBq/m³,平均值为6.84 mBq/m³。²¹⁰Pb放射性活度浓度的变化范围为0.01~9.37 mBq/m³,平均值为3.19 mBq/m³。2017—2020年北京大气气溶胶⁷Be和²¹⁰Pb放射性活度浓度在春、夏、秋、冬四季中差异均有统计学意义（F=32.66、93.93,P<0.05）,其中⁷Be放射性活度浓度春季最高,秋季次之,夏季和冬季最低,²¹⁰Pb放射性活度浓度由高到低分别为冬季、秋季、春季、夏季。结论 2017—2020年北京地区大气气溶胶中⁷Be和²¹⁰Pb放射性活度浓度处于正常涨落水平范围内。     

99Tcm-3P4-RGD2 microSPECT/CT显像评价抗新生血管治疗肿瘤疗效价值的实验研究

目的探讨整合素α_vβ₃受体靶向microSPECT/CT显像在抗新生血管治疗肿瘤效果中的应用价值。方法构建荷人脑胶质瘤（U87MG）和荷人前列腺癌（PC-3）裸鼠模型。在肿瘤直径为6.0~7.0 mm时,分别给予Avastin治疗,并以生理盐水为对照组,在Avastin给药前1 d、给药后3、5、10和15 d,分别行⁹⁹Tc^m-3P4-RGD₂ microSPECT/CT显像,测定肿瘤体积和放射性百分注射剂量率（% ID和% ID/g）摄取。监测荷瘤鼠一般情况,按照随机数字表法,在每个显像时间点取1只处死,进行病理学检查。结果 U87MG治疗组肿瘤体积在治疗后10 d明显小于U87MG对照组（t=5.81,P<0.05）,差异有统计学意义,PC-3治疗组与PC-3对照组肿瘤体积差异无统计学意义（P>0.05）;U87MG治疗组肿瘤对⁹⁹Tc^m-3P4-RGD₂摄取（% ID/g）在治疗前高于PC-3（t=10.48,P<0.05）,给药后3 d低于U87MG对照组（t=3.26,P<0.05）,且随着治疗进行逐渐减少,PC-3治疗组和对照组肿瘤摄取（% ID/g）均较低。病理结果显示,U87MG治疗组整合素β₃表达降低以新生血管内皮为主,肿瘤细胞呈缓慢降低,U87MG肿瘤摄取（% ID/g）与整合素β₃表达呈线性相关y=0.499 1x-0.243 8（R²=0.811 7）。结论Avastin治疗脑胶质瘤早期表现为新生血管整合素受体β₃表达显著降低,⁹⁹Tc^m-3P4-RGD₂ microSPECT/CT显像预期可作为脑胶质瘤抗新生血管治疗疗效早期评价的无创性手段。     

99Tcm-亚甲基二膦酸盐SPECT骨显像患者的周围辐射水平及其影响因素

目的 对⁹⁹Tc^m-亚甲基二膦酸盐（MDP）单光子发射计算机断层成像术（SPECT）骨显像患者周围辐射水平及其影响因素进行研究,为保证周围人员辐射安全提供实验依据。方法 对367例中国医学科学院肿瘤医院全身骨显像的患者进行测量,测量其不同时间及不同距离处的周围剂量当量率,分析周围剂量当量率随时间及距离的变化规律,估算周围不同距离处的剂量水平,评估周围人员的辐射剂量。结果 患者周围剂量当量率随时间指数衰减,患者体内⁹⁹Tc^m有效半衰期随时间增加;周围剂量当量率距患者4 m内随距离的变化呈幂函数,平均幂值为-1.45。从患者注射⁹⁹Tc^m药物至患者体内⁹⁹Tc^m基本消失,在距患者0.5、1.0和1.5 m处的周围辐射剂量水平分别为238.3、99.7和61.8 μSv;在注射后不同的时间点（0、3和6 h）,与患者距0.5 m滞留10 min,辐射剂量分别为9.9、3.0和1.9 μSv。结论 骨显像患者周围剂量当量率随时间和距离快速降低。骨显像患者会对周围人员造成一定的照射,但是剂量水平远低于国家标准的规定。建议患者进行骨显像的当天尽量不要进行和医护人员长时间近距离接触的其他诊疗。     

131I标记纳米脂质体靶向治疗结肠癌的实验研究

目的 研究¹³¹I-antiEGFR-BSA-PCL对LS180细胞结肠癌裸鼠移植瘤内照射的治疗效果。方法 构建抗表皮生长因子受体(EGFR)标记的纳米脂质体及EGFR靶向性。通过荧光共聚焦显微镜、细胞摄碘实验观察纳米载体的靶向性及LS180细胞对其摄取情况。将裸鼠40只按随机数字表法分为4组,通过瘤体内注射的方式向移植瘤内分别注射74 MBq (740 MBq/ml) ¹³¹I-antiEGFR-BSA-PCL、¹³¹I-BSA-PCL、¹³¹I及相同体积的生理盐水。通过研究裸鼠体重、肿瘤体积、SPECT显像及组织病理学方法,观察纳米脂质体的抑瘤效果。结果 共聚焦实验显示,与BSA-PCL组相比,antiEGFR-BSA-PCL组细胞内绿色荧光较明显,其介导的胞吞效应显著。摄碘率实验中,LS180细胞对¹³¹I-antiEGFR-BSA-PCL的摄取率明显高于¹³¹I-BSA-PCL(t=2.77~5.40,P<0.01)。¹³¹I-antiEGFR-BSA-PCL组与¹³¹I-BSA-PCL组裸鼠肿瘤增殖均较慢,二者差异无统计学意义(P>0.05)。给药后72 h,¹³¹I-antiEGFR-BSA-PCL与¹³¹I-BSA-PCL的肿瘤摄取率分别为(21.61±1.01)和(20.58±0.65)% ID/g,均明显高于¹³¹I组(t=9.36、8.69,P<0.01)。SPECT显像显示纳米脂质体主要特异性积聚在肿瘤区。结论 ¹³¹I-antiEGFR-BSA-PCL对LS180结肠癌裸鼠移植瘤有明显的抑制作用。     

肝胆肿瘤患者68Ga-FAPI-04 PET显像的内照射剂量及分布研究

目的 评估⁶⁸Ga-FAPI-04 PET/CT检查在肝胆肿瘤患者中的内照射剂量及生物分布。方法 本研究纳入因肝脏占位于北京协和医院接受PET/CT检查的6例患者,经静脉注射⁶⁸Ga-FAPI-04（170.57 ±14.43） MBq后分别于第3、10、15、20、30和60 min进行全身显像。观察显像剂的生物分布;手动勾画感兴趣区;所有靶器官的内照射剂量应用OLINDA/EXM软件计算。结果 ⁶⁸Ga-FAPI-04在肝脏内放射性本底消退较快,在肿瘤组织内放射性摄取较为稳定,病灶平均SUV_max在注射后20 min达到最大（13.87 ±2.55）;病灶平均靶本比逐渐升高,在注射后30 min达到最大（10.09 ±8.17）。1次⁶⁸Ga-FAPI-04 PET/CT扫描的全身有效剂量为（0.020 ±0.002） mSv/MBq,吸收剂量最高的器官是膀胱壁,为（0.146 ±0.035） mSv/MBq。结论 ⁶⁸Ga-FAPI-04与¹⁸F-FDG全身有效剂量相近;肿瘤摄取快速,肝脏背景低,且不受血糖水平影响,有望成为潜在的肝胆肿瘤PET/CT显像药物。     

131I标记抗表皮生长因子受体抗体靶向性纳米载体治疗胶质母细胞瘤的可行性实验研究

目的 构建¹³¹I标记抗表皮生长因子受体抗体(antiEGFR)靶向性的纳米载体,探讨其在细胞水平和动物体内用于胶质瘤治疗的可行性。方法 制备放射性碘(¹³¹I)标记的antiEGFR靶向性的纳米载体牛血清白蛋白聚己内酯复合物¹³¹I-antiEGFR-BSA-PCL。用共聚焦显微镜观察纳米载体能够与肿瘤细胞结合情况,用MTT法检测纳米载体的细胞毒性作用,摄碘率实验检测肿瘤细胞对放射性纳米载体的摄取。制备裸鼠种植瘤模型,通过瘤体内注射给药,观察裸鼠种植瘤的体积变化,通过SPECT显像观察药物在裸鼠体内的停留情况,并分析纳米载体在裸鼠体内的分布情况。结果 成功地制备了BSA-PCL及antiEGFR-BSA-PCL纳米载体。与BSA-PCL相比,antiEGFR-BSA-PCL更容易与肿瘤细胞结合。当放射性纳米载体的放射性活度达到0.925 MBq时,U251和U87细胞的生长抑制率¹³¹I-antiEGFR-BSA-PCL组均高于¹³¹I-BSA-PCL组(t=2.517、2.821,P<0.05),且均高于同组其他剂量(U251:t=2.148、2.693,P<0.05;U87:t=2.436、2.615,P<0.05)。裸鼠体内实验发现两种纳米载体瘤体内注射后均经过肝脏代谢。¹³¹I-antiEGFR-BSA-PCL组荷瘤裸鼠的种植瘤体积较¹³¹I-BSA-PCL组缩小更多(t=4.115,P<0.05)。结论 ¹³¹I-antiEGFR-BSA-PCL在体内外实验中均能够抑制胶质瘤生长,为胶质瘤的治疗和预后评估提供了一种新方法。     

放射性药物99mTc-HL91在大鼠脑缺血模型的初步研究

目的 探讨国内首次合成的放射性药物＾９９ｍＴｃ－ＨＬ９１在脑血管疾病诊断中的应用的可能性。方法 对＾９９ｍＴｃ－ＨＬ９１进行一般性质、标记率、体外稳定性、异常毒性和正常小鼠体内生物分布等实验。建立１５只大鼠脑缺血模型,并在该模型上进行＾９９ｍＴｃ－ＨＬ９１体内分布和乏氧显像研究。结果（１）ＨＬ９１药盒标记简便,安全稳定,（２）正常小鼠静脉注射＾９９ｍＴｃ－ＨＬ－９１后血中放射性迅速下降,肝、肾和胃     

The preparation and biological characterization of a new HL91-derivative for hypoxic imaging on stroke mice

Aim^99mTc-HL91 (Prognox, GE-Healthcare) was the first nonnitro-aryl-based radiotracer for evaluating hypoxic fraction in neoplasm, stroke and myocardium infarction regions. However, the high hydrophilicity of ^99mTc-HL91 might hamper its penetration into cells. In this study, we prepared a new ligand 4,4,11,11-tetramethyl- 5,10-diazatetradecane- 3,12-dionedioxime (HL91-ET) with higher lipophilicity but structurally similar compared with that of HL91. The chemical and biological characterizations of ^99mTc-HL91-ET as a scintigraphic probe for hypoxia were performed with a stroke-bearing mouse model.Materials and MethodsHL91-ET was synthesized and formulated with stannous chloride and buffer to afford kits. After mixing with ^99mTc-pertechnetate, ^99mTc-HL91-ET can be prepared in high yield and high radiochemical purity (both >96%). The partition coefficient of ^99mTc-HL91-ET was determined in n-octanol/PBS system. Cellular uptake assays under normoxic and hypoxic conditions were performed in an oxygen-controlled CO₂ incubator. Brain stroke in the mouse model was induced by the electrocautery of the middle cerebral artery. After intravenous injection of ^99mTc-HL91-ET into the Balb/c mouse suffering brain stroke, small-animal SPECT images were acquired at designated time points and autoradiography of the brain slides was conducted. Parallel studies of ^99mTc-HL91 were also conducted at the same conditions for comparison.ResultsThe higher partition coefficient of ^99mTc-HL91-ET (0.294±0.007) indicated higher lipophlicity compared with that of ^99mTc-HL91 (0.089±0.005). The ^99mTc-HL91-ET preparation was stable at ambient temperature for 24 h. Cellular uptake assay showed that ^99mTc-HL91-ET was less selectively retained in hypoxic cells than ^99mTc-HL91. The target-to-normal brain ratios derived from the autoradiograms of the brains of stroke mice were 1.31±0.02 and 17.47±0.10 (n=3), respectively, at 2 h post injection of ^99mTc-HL91-ET and ^99mTc-HL91.ConclusionsThis study revealed that ^99mTc-HL91-ET, though with higher lipophilicity than ^99mTc-HL91, did not suggest better specific accumulation in hypoxic cells or tissues than ^99mTc-HL91. The uptake mechanism of ^99mTc-HL91 was at least not solely by passive diffusion. Lipophilicity should not be the major consideration in designing HL91-derivatives for hypoxia imaging.     

Assessment of reperfused myocardium using a new ischaemia-avid imaging agent, technetium-99m HL91: comparison with myocardial glucose uptake

We evaluated the efficacy of a new ischae-mia-avid imaging agent, technetium-99m labelled 4,9-diaza-3,3,10,10-tetramethyldodecan-2,11-dione dioxime (^99mTc- HL91) as a marker of myocardial viability in ischaemic and reperfused myocardium. The left coronary artery of rats was ligated for 15 or 60 min and released. The myocardium was reperfused for 60 min [stunned myocardium, or acute myocardial infarction (MI)] or 7 days (subacute MI). Thereafter, ^99mTc-HL91 and carbon-14 2-deoxyglucose (DG) were co-injected 30 min before sacrifice. We evaluated the myocardial accumulation of ^99mTc-HL91 and DG by dual-tracer ex vivo autoradiography. The uptake of each tracer in the myocardial region was normalized by that in the septum (control), and expressed as percent uptake (%HL or %DG, respectively). Individual hearts were also histopathologically examined. The %HL in the stunned myocardium (n = 8) and in the septum were identical (101%±15%, mean±SD, P = ns), whereas the %DG was significantly increased (149%±27%, P<0.05) compared with that in the septum. These results suggest that ^99mTc-HL91 cannot visualize stunned myocardium, whereas DG can. In acute MI (n = 7), the %HL (423%±96%, P<0.005) and the %DG (318%±91%, P<0.001) in the non-infarcted area at risk were significantly augmented compared with those in the septum. The %DG (181%±17%) in the infarcted area was also augmented (P<0.001), whereas the %HL (106%±25%) in the infarcted area was identical to that in the septum (P = ns). These results indicate that ^99mTc-HL91 detected viable myocardium in the area at risk. In subacute MI (n = 8), the%HL in the infarcted area (101%±45%) and in the septum was identical, whereas %DG (292%±57%) was significantly higher than that in the non-infarcted risk area or the septum (P<0.0001). These findings suggest that DG detected viable myocardium in the area at risk, but that ^99mTc-HL91 was not retained. We conclude that ^99mTc-HL91 is a potent marker of myocardial viability when used during the early acute phase after reperfusion. Received 9 September and in revised form 17 December 1997     

EGF receptor targeted tumor imaging with biotin-PEG-EGF linked to 99mTc-HYNIC labeled avidin and streptavidin

IntroductionAs direct radiolabeled peptides suffer limitations for in vivo imaging, we investigated the usefulness of radioloabeled avidin and streptavidin as cores to link peptide ligands for targeted tumor imaging.MethodsHuman epidermal growth factor (EGF) was site specifically conjugated with a single PEG-biotin molecule and linked to ^99mTc-HYNIC labeled avidin-FITC (Av) or streptavidin-Cy5.5 (Sav). Receptor targeting was verified in vitro, and in vivo pharmacokinetic and biodistribution profiles were studied in normal mice. Scintigraphic imaging was performed in MDA-MB-468 breast tumor xenografted nude mice.ResultsWhereas both ^99mTc-Av-EGF and ^99mTc-Sav-EGF retained receptor-specific binding in vitro, the two probes substantially diverged in pharmacokinetic and biodistribution behavior in vivo. ^99mTc-Av-EGF was rapidly eliminated from the circulation with a T1/2 of 4.3 min, and showed intense hepatic accumulation but poor tumor uptake (0.6%ID/gm at 4 h). ^99mTc-Sav-EGF displayed favorable in vivo profiles of longer circulation (T1/2β, 51.5 min) and lower nonspecific uptake that resulted in higher tumor uptake (3.8 %ID/gm) and clear tumor visualization at 15 h.Conclusion^99mTc-HYNIC labeled streptavidin linked with growth factor peptides may be useful as a protein-ligand complex for targeted imaging of tumor receptors.     

Application of lectins to tumor imaging radiopharmaceuticals

We investigated the in vitro binding of ¹²⁵I-lectins to Ehrlich ascites tumor (EAT) cells and in vivo uptake of ¹²⁵I-lectins in Ehrlich solid tumor (EST) bearing mice. In in vitro binding assays, phaseolus vulgaris agglutinin (PHA), pisum sativum agglutinin (PSA), and concanavalia agglutinin (Con A) showed a high affinity for EAT cells. The in vivo biodistribution of ¹²⁵I-lectins showed ¹²⁵I-PSA to be significantly taken up into EST tissues 24 h postinjection. After IV injection of ¹²⁵I-PSA, uptake of the radioactivity into the tumor tissues reached a maximum at 6 h, and thereafter decreased. Rapid clearance of the radioactivity from blood and its exretion into kidney soon after injection of ¹²⁵I-PSA were observed. When compared with the biodistribution of ⁶⁷Ga-citrate in EST bearing mice 24 h postinjection, tumor to liver (T/B), tumor to muscle (T/M), and tumor to blood (T/B) ratios were superior for ¹²⁵I-PSA. At 6 h postinjection, the T/B-ratio of ¹²⁵I-PSA was 2.5, and this value may be sufficient to enable discernable diagnostic images. Our results suggest that PSA might be a useful tumor imaging radiopharmaceutical.     

Appropriate collimators in a small animal SPECT scanner with CZT detector

Objective

Almost all small animal SPECT is performed with pinhole collimators (PH), including single-PH (SPH) and multi-PH (MPH). In the clinical study, not only PH but also parallel-hole collimator (PAH) is often used in planar and SPECT imaging. However, there have been no comparative studies on image quality with various collimators on the small animal imaging. This study compared the basic characteristics of PH and PAH in small animal imaging.

Methods

Performance of planar and SPECT images was evaluated using ^99mTcO₄ ^? and SPH, MPH and PAH with low energy and high resolution on the SPECT/CT scanner FX3200. We measured sensitivity, resolution, concentration linearity and uniformity. Planar imaging of mice with ^99mTc-labeled mercaptoacetyltriglycine (^99mTc-MAG₃) was performed using SPH and PAH. SPECT imaging with ^99mTc-methylene diphosphonate (^99mTc-MDP) was performed using all collimators.

Results

With SPH, MPH and PAH, sensitivity was 43.5, 211.2 and 926.5 cps/MBq, respectively, and spatial resolution was 0.60/0.56, non/0.96, 5.20/5.34 mm full-width half maximum (planar/SPECT), respectively. There were marked correlations between the radioactivity counts on images and radioactivity with all collimators. Values of % standard deviation on planar imaging showed small differences between the SPH and PAH, while the values were the smallest on SPECT imaging with MPH. On imaging of mice, SPH yielded high-quality ^99mTc-MAG₃-planar images when compared with PAH. MPH yielded sharper ^99mTc-MDP-SPECT images than SPH and PAH.

Conclusions

The characteristics of PH and PAH differed on small animal imaging. Although sensitivity was higher with PAH, PH showed higher resolution. Among the PH collimators, SPH was more appropriate for planar imaging, and MPH was more suitable for SPECT imaging in a small animal imaging scanner with CZT detector.     

Radiosynthesis,molecular modeling studies and biological evaluation of 99mTc-Ifosfamide complex as a novel probe for solid tumor imaging

Purpose: Ifosfamide as a chemotherapeutic drug is used for the treatment of different cancer types. The purpose of this study is the preparation of ^99mTc-ifosfamide complex to be evaluated as a potential candidate for tumor imaging.

Materials and methods: The radiolabeling of ifosfamide with technetium-99m was carried out by mixing 4mg ifosfamide and 5?μg of SnCl₂.2H₂O with 400 MBq Na^99mTcO₄ at pH 9 for 30?min at room temperature. Computer simulation studies were performed using Accelrys Discovery Studio 2.5 operating system to illustrate the interaction of ifosfamide and ^99mTc-ifosfamide complexes with DNA. The in-vivo biodistribution of ^99mTc-ifosfamide was studied in tumor-bearing Albino mice.

Results: A new ^99mTc-ifosfamide complex was synthesized with a good radiochemical yield of 90.3?±?2.1% under the optimized conditions and exhibited in-vitro stability up to 2?h. Biodistribution studies showed good uptake in tumor site and high uptake in tumor site with T/NT ～3 after 60?min post-injection. Besides, the molecular docking study confirmed that the complexation of ifosfamide with technetium-99m does not abolish its binding to the target receptor.

Conclusion: These promising results afford a new radiopharmaceutical that could be used as a potential tumor imaging     

Imaging of intraperitoneal tumors with technetium-99m GSA

^99mTc labeled galactosyl serum albumin (GSA) has been used clinically as a receptor-binding agent for the assessment of liver function. The aim of this study was to investigate the usefulness of^99mTc-GS A in intraperitoneal (i.p.) tumor imaging. A tumor model was established by i.p. inoculating nude mice with human ovarian cancer cell SHIN-3, or colon cancer cell LS180. Radiolabels were i.p. injected into the tumor-bearing mice and the biodistribution of radioactivity was examined. After administration,^99mTc-GSA rapidly accumulated in the tumor. The tumor uptake was 5.82-8.46 %ID/g from 30 min to 6 h after the injection. Radioactivity in the blood was very low, less than 0.3 %ID/g, resulting in high tumor-to-blood ratio. Tumors could be clearly seen by scintigraphic imaging. Accumulation of i.p.-injected^99mTc labeled human serum albumin (HSA) in i.p. tumors was similar to that of^99mTc-GSA, but radioactivity of^99mTc-HSA in the circulation was high, resulting in a significantly lower tumor-to-blood ratio. In conclusion,^99mTc-GSA, when i.p. injected, accumulated in i.p. tumors and cleared from circulation rapidly, which would make it useful for the imaging of i.p. tumors.     

Pretargeting CWR22 prostate tumor in mice with MORF-B72.3 antibody and radiolabeled cMORF

Purpose We have now applied our MORF/cMORF pretargeting technology to the targeting of CWR22 prostate tumor in nude mice. Methods The antiTAG-72 antibody B72.3 was conjugated with an 18 mer MORF while the cMORF was radiolabeled with ^99mTc. The specific binding of the antibody to the CWR22 cells was first confirmed in an assay placing the radiolabeled B72.3 antibody in competition with increasing concentrations of native B72.3. Thereafter, a group of four CWR22 tumored mice intravenously received the MORF-B72.3 and, 3 days later, the ^99mTc-cMORF, and were killed at 3 h postradioactivity injection. The dosage of the labeled cMORF was selected on the basis of previous experience in LS174T tumored mice. As controls, four animals received only the radiolabeled cMORF and another four received only the ¹¹¹In-B72.3. The maximum percent tumor accumulation (MPTA) of the labeled cMORF was subsequently determined by a dosage study of labeled cMORF. Both a multipinhole SPECT image and a planar gamma camera image were obtained of a representative mouse. Results The CWR22 tumor was confirmed to be TAG-72-positive. The MPTA of the labeled cMORF in the CWR22 tumor was 2.22%ID/g compared to only 0.12%ID/g in control mice without pretargeting. Both the planar and tomographic images confirmed the success of the CWR22 pretargeting. Conclusions The MORF/cMORF pretargeting approach has been successfully applied to tumor targeting of the prostate xenograft CWR22. However, the MPTA in this tumor model is lower than that in the LS174T tumor model investigated earlier, possibly due to a lower tumor blood supply. Financial support: CA107360 and CA94994.