分化型甲状腺癌患者口服131I后体内活度变化及剂量水平

目的 研究¹³¹I治疗分化型甲状腺癌（DTC）患者体内放射性活度及外部剂量水平的变化规律，分析二者之间的关系，并估算400 MBq患者剂量当量率的修正因子。方法 研究对象为43例甲状腺全切术后，首次行¹³¹I"清甲"治疗的DTC患者，服药量为1 850~3 700 MBq，平均服药量（2 405±777）MBq。分别于口服¹³¹I后2、6、20、22、24、27、30、44、46、48、54、68及72 h，测定患者的体内剩余放射性活度以及患者前部0.3、1及3 m处的剂量当量率。结果 患者服¹³¹I后的体内剩余放射性活度随时间变化函数为A=A₀（1.033 16e^{-0.062 4t}+0.017 17）。可估算出"清甲"治疗的DTC患者有效半减期为12.19 h，体内放射性活度降至400 MBq仅需26.4~38.9 h。患者服用¹³¹I后距其0.3、1及3 m的标准化剂量当量率随时间变化函数分别为：Ḣ_0.3=127.220 7e^{-0.054 8t}+3.765 71、Ḣ₁=30.225 8e^{-0.064 4t}+0.824 67、Ḣ₃=4.161 9e^{-0.061 5t}+0.167 97。患者服¹³¹I后体内剩余放射性活度与1 m处剂量当量率呈正相关（r=0.982，P<0.05），函数为Ḣ₁=0.025A+1.245。DTC患者体内剩余活度分别为1 000、700和400 MBq时，距患者1 m处对应的剂量当量率分为26.2、18.7和11.2 μSv/h。估算活度为400 MBq的患者0.3、1及3 m处剂量当量率的修正因子分别为0.25、0.49及0.70。结论 服用¹³¹I活度在3 700 MBq以下的DTC患者仅需住院2日便可达到出院标准。当DTC患者体内活度降至400 MBq时，其1 m处的剂量当量率远小于25 μSv/h。单纯利用点源公式估算患者周围剂量当量率会造成高估的情况，因此对于公式估算患者周围辐射水平时使用的修正因子还需进一步研究，使模型估算结果更贴合实际情况。     

分化型甲状腺癌患者131I治疗后体内残留放射性活度的评估

目的 评估分化型甲状腺癌(DTC)患者¹³¹I治疗后体内残留放射性活度.方法 本次前瞻性研究包括49例DTC患者,分为“清甲”(¹³¹I摧毁术后残留的甲状腺组织)与“清灶”(¹³¹I治疗甲状腺床残留甲状腺癌、甲状腺床复发灶和转移灶)组,于服¹³¹I后收集患者每次排泄尿液,测定患者每天每次通过尿液排泄的放射性活度及排泄的总放射性活度,进而估算患者体内残留的放射性活度.分别于服¹³¹I后2、6、24、48、72 h进行1 m处剂量当量率的测定,估算患者体内残留放射性活度达到400 MBq时1 m处剂量当量率.结果 服¹³¹I后2、6、24、48、72 h体内残留¹³¹I活度占服¹³¹I初始活度的百分比,“清甲”组分别为99%、72%、25%、15%、7%,1 m处剂量当量率分别为157、120、35、11、9 μSv/h;"清灶"组对应百分比分别为99%、71%、18%、7%、3%,1 m处剂量当量率分别为232、182、48、11、2 μSv/h.体内残留的放射性活度与1 m处剂量当量率呈正相关(r=0.94,P<0.001).“清甲”与“清灶”组服¹³¹I后48~72 h体内残留放射性活度分别为548~259及451~248 MBq,对应的1 m处剂量当量率为8~10 μSv/h.结论 DTC患者于服¹³¹I后48~72 h体内残留放射性活度达到国家标准规定的400 MBq,即DTC患者1 m处剂量当量率达到8~10 μSv/h方可出院.     

分化型甲状腺癌患者131I治疗后体内放射性总活度的变化及影响因素

目的 探讨¹³¹I治疗分化型甲状腺癌(differentiated thyroid carcinoma,DTC)术后患者体内放射性总活度的变化及其代谢的影响因素。方法 回顾性分析2021年9月至2022年4月于空军军医大学第二附属医院核医学科接受¹³¹I治疗的218例DTC术后患者的临床资料,根据服用¹³¹I的剂量分为低剂量组(≤3.7 GBq)171例和高剂量组(＞3.7 GBq)47例,使用全身动态辐射监测系统在服用¹³¹I后24、48及72 h测定体内¹³¹I残留活度并探讨其变化的影响因素。结果 服用¹³¹I后低剂量组24、48及72 h的体内¹³¹I残留活度均明显低于高剂量组(t=-7.46、-3.31、-2.01,P<0.05);低剂量组24、48 h出院达标率明显高于高剂量组(21.0%vs. 4.3%、98.2%vs. 89.4%,χ²=7.23、5.91,P<0.05),且所有患者在72 h均可达出院标准。单因素分析显示患者24及48 h体内¹³¹I残留活度与年龄、体质量指数(body mass index,BMI)、基础代谢率(basal metabolism rate,BMR)及促甲状腺激素(thyroid stimulating hormone,TSH)有关。多元线性回归分析显示低剂量组24 h时年龄越大、BMR越高、TSH水平越高,体内¹³¹I残留活度越大,48 h时BMI越大、TSH越高,体内¹³¹I残留活度越大;高剂量组24 h时年龄越大、BMR越高,体内¹³¹I残留活度越大。患者体内¹³¹I残留活度达到400 MBq的时间以24、36 h来分析其影响因素,结果显示以24 h为分界时,TSH水平越低,体内¹³¹I残留活度越低;以36 h为分界时,年龄越小、TSH水平越低、¹³¹I治疗剂量越小,体内¹³¹I残留活度越低。结论 年龄、BMI、BMR及TSH水平是¹³¹I治疗DTC术后患者体内放射性总活度的影响因素,联合上述指标进行辐射剂量评估可为调整患者住院时长提供参考。     

呋塞米介入对18 F-脱氧葡萄糖正电子发射计算机断层显像的放射防护作用

目的 探讨呋塞米介入¹⁸F-脱氧葡萄糖(¹⁸F-FDG)正电子发射计算机断层显像(PET/CT)的放射防护作用。方法 146例患者按随机数表法随机分为两组,实验组74例,对照组72例。试验组注射前口服呋塞米40 mg,正常对照组未行特殊处理,¹⁸F-FDG注射60、120 min后,分别在其正面前胸、腹水平测量0.5 m处周围剂量当量率。结果 试验组注射¹⁸F-FDG后60 min胸部及腹部、120 min胸部及腹部的周围剂量当量率分别为(30.80±8.61)、(41.38±11.06)、(18.26±4.85)和(24.66±6.50)μSv/h,均低于对照组,差异有统计学意义(t=15.36、13.13、18.73、17.29,P＜0.05)。试验组和对照组的纵隔SUV_max、肝脏SUV_max差异无统计学意义(P＞0.05)。多因素分析显示,是否服用速尿、体表面积是影响周围剂量当量率的主要影响因素(t=-13.52、2.96,P＜0.05),年龄、性别对周围剂量当量率的影响不明显(P＞0.05)。结论 呋塞米介入可促进排尿,在不影响影像质量的前提下有效降低了受检者的体内辐射,有较好的放射防护作用。     

腹盆腔肿瘤125I粒子植入术后个体化防护临床研究

目的 研究腹盆腔肿瘤患者¹²⁵I粒子植入术后周围环境的受照剂量率及有效剂量,为不同人群的安全防护提供参考。方法 采用袖珍辐射仪,监测42例腹盆腔肿瘤患者¹²⁵I粒子植入术后24 h内,距离植入部位各方向不同距离的受照剂量率,比较不同方向不同距离的剂量率差异。对植入粒子的总活度与测量的剂量率及植入深度与标准活度下剂量率进行曲线拟合并得出关系方程。根据公式计算不同人群、不同距离受照射的剂量率与警戒时间的关系。结果 距垂直粒子植入部位30、50、100 cm的受照剂量率分别为（6.92±2.87）、（4.10±1.62）和（1.30±0.48）μSv/h,差异有统计学意义（χ²=73.71,P<0.05）。患者左、右侧面30、50、100 cm受照剂量率分别为（0.378±0.156）和（0.384±0.153）μSv/h、（0.170±0.089）和（0.176±0.086）μSv/h、（0.039±0.014）和（0.043±0.017）μSv/h,差异均有统计学意义（χ²=76.19、76.33,P<0.05）。垂直粒子植入部位的受照剂量率与植入粒子总活度及标准活度下剂量率与植入深度呈线性关系。患者对同住成年人无警戒时间,同床成年人、接触同事、同住未成年人及孕妇的警戒时间与剂量率的关系公式分别为：t（d）=-106.616+83.779lnD（t）、t（d）=26.556+85.933lnD（t）、t（d）=3.088+85.017lnD（t）。结论 ¹²⁵I粒子植入术后患者,监测其周边环境的辐射剂量在辐射安全范围内;且随着植入粒子总活度的减小及植入深度的增大剂量率减小;同时根据术后测得的剂量率或植入粒子的总活度、植入粒子的深度计算不同人群的警戒时间,进行个体化防护。     

125I粒籽源植入中职业人员眼晶状体和手部受照剂量分析

目的 用热释光剂量计（TLD）和光致发光剂量计（OSLD）测量¹²⁵ I粒籽源植入过程中职业人员眼晶状体和手部皮肤剂量,并进行对比分析。方法 从同批次中,选取TLD退火,包装,贴在仿真人模体腹部平坦处,¹²⁵ I粒籽源放在与模体相同高度,距离15 cm处,分别照射不同剂量：1.0、1.5、3.0、5.0、10.0、12.0、20.0、25.0、30.0、50.0、60.0μGy,照射后的TLD经热释光测量仪测量,建立标准空气比释动能刻度曲线;选择2家医院4个部位：肺部14例、腹部10例、盆腔5例和颈部6例进行¹²⁵ I粒籽源植入治疗,将刻度完的TLD分别贴在职业人员眼部的左、中、右位置,手部左、右位置,进行测量,得到相应部位的空气比释动能值,最后用眼部H_p（3）转换因子和手部H_p（0.07）转换因子分别计算职业人员眼晶状体和手部皮肤剂量当量值。同时建立OSLD测量方法,将退火后的OSLD放在与TLD相同位置直接测量职业人员眼晶状体和手部皮肤剂量当量。结果 ¹²⁵ I粒籽源植入治疗过程中,应用TLD测量得到手术医生和助手的眼晶状体累积剂量当量分别为0.8和1.6 mSv（肺部）、1.3和1.2 mSv（腹部）、0.9和0.6 mSv（盆腔）、均为0.3 mSv（颈部）;手部累积剂量当量分别为1.4和2.1 mSv（肺部）、1.2和1.0 mSv（腹部）、0.5和0.9 mSv（盆腔）、均为0.1 mSv（颈部）;单次手术植入时,职业人员眼晶状体和手部接受的最大剂量当量分别为1.2和1.0 mSv。应用OSLD测量得到肺部治疗时手术医生和助手的眼晶状体累积剂量当量分别为0.2和0.1 mSv,手部累积剂量当量分别为0.4和0.6 mSv;腹部治疗时手术医生手部累积剂量当量为0.1 mSv;其他部位治疗时不同职业人员的剂量当量值均为0 mSv。结论 TLD不仅能给出累积剂量当量,也能给出单次手术的剂量当量,按照ICRP 118号报告修订后规定的职业人员眼晶状体限值,本实验中以单次治疗时眼晶状体接受的最大剂量当量估算,则每年植入病例数不应超过17例。OSLD只能给出累积剂量,测量低剂量的准确性有待研究。     

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。     

组织成分及密度对125I粒子植入剂量分布影响的研究

目的 分析组织成分及密度对¹²⁵I粒子植入剂量分布影响,为临床放射性粒子植入剂量计算和评估提供参考。方法 应用egs_brachy软件建立OncoSeed 6711型¹²⁵I放射性粒子物理模型,计算剂量率常数和水中径向剂量函数g（r）,以验证计算模型准确性;根据不同组织的元素组成及密度表,分别计算¹²⁵I粒子在水、前列腺、乳腺、肌肉、骨等不同介质中g（r）和剂量分布。结果 计算得到的剂量率常数为0.950 cGy·h^-1·U^-1、水中g（r）和吸收剂量均与文献数据近似。在同一径向位置,¹²⁵I粒子在前列腺、肌肉中吸收剂量与水中差异<5%;在距源中心0.05 cm处,骨中吸收剂量是水中的6.042倍;在近源1.7 cm内,乳腺与水中吸收剂量差异均>10%。结论 ¹²⁵I粒子在部分介质中的剂量分布与水有着较明显区别,在临床剂量计算中需考虑组织成分及密度对吸收剂量的影响。     

125I粒子和60Co γ射线照射对A549及BEAS-2B细胞生物学效应的影响

目的 探讨¹²⁵I粒子和⁶⁰Co γ射线对非小细胞肺癌(NSCLC)A549细胞和正常支气管上皮BEAS-2B细胞生物学效应的影响。方法 A549、BEAS-2B细胞均行¹²⁵I粒子和⁶⁰Co γ射线不同剂量照射;集落形成实验检测细胞存活分数;流式细胞术检测细胞周期和细胞凋亡率;Western blot检测凋亡相关蛋白的表达水平。结果 A549细胞在4、6、8 Gy照射时,¹²⁵I粒子组细胞克隆存活分数较⁶⁰Co组降低更明显(t=6.06、9.42、4.90,P<0.05)。A549细胞在4 Gy时,G₁期细胞比例¹²⁵I粒子组为70.67%±1.49%,⁶⁰Co组为59.59%±0.71%(t=10.77,P<0.05);细胞凋亡率¹²⁵I粒子组为18.09%±0.73%,⁶⁰Co组为9.81%±0.16%(t=19.40,P<0.05)。¹²⁵I粒子照射明显上调Bax、cleaved Caspase-3蛋白的表达,同时下调Bcl-2蛋白的表达。但不同射线同一剂量或相同射线不同剂量下,BEAS-2B细胞的凋亡率及凋亡相关蛋白的表达无明显变化。结论 ¹²⁵I粒子持续低剂量率照射较⁶⁰Co γ射线高剂量率照射抑制A549细胞增殖的效应更明显。Bcl-2/Bax蛋白比失衡,最终致Caspase-3蛋白的活化在¹²⁵I粒子持续低剂量率照射抑制肿瘤细胞增殖的效应中可能发挥重要的作用。     

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。     

人体中的镭-226、镭-228、钋-210、铅-210

本文报道了广东阳江高本底地区6名、对照地区8名人尸体的骨²²⁶Ra、²²⁶Ra的浓度以及部分居民内脏器官中。²¹⁰Po、²¹⁰Pb的浓度。结果轰明阳江高本底地区和对照地区居民骨镭-226、镭-228的浓度分别为29.9pCi/kg, 26.9pCi/kgl 8.7pCi/kg, 8.2pCi/kg.由此估算出阳江高本底地区屠民骨中²²⁶Ra、²²⁸Ra的负薄璧及对骨衬、骨髓所产生的剂量当量分别为对照地区民民的3.4倍, 3.3倍。两地区居民内脏器官中^{210Po、210Pb的测定分析铡数较少但仍看出, 高本底地区均明显高于对照地区.}     

226Ra 228Ra 210Pb和210Po在水生生物及食物链中转移规律的探讨

目的 为了解天然放射性核素²²⁶Ra、²²⁸Ra、²¹⁰Pb与²¹⁰Po在水生物及食物链中转移和蓄积情况。方法 定点采集养殖水产品及栖息环境中水与底质沉积物, 按不同的实验需要, 每个鲜样分别剥取肉, 骨(壳),鳞片和胃肠。烹饪样品, 洗净、称重、清炖, 熟后分离出骨(壳),余为食物。样品分别测定²²⁶Ra、²²⁸Ra、²¹⁰Pb和²¹⁰Po含量。数据按统计学要求处理, 配对数据, 作了配对显着性检验。结果 ²²⁶Ra、²²⁸Ra和²¹⁰Pb主要沉积于骨(壳)中, 浓集系数为10²～10³,肉中为10⁰～10².²¹⁰Po主要蓄积在水生物胃肠中, 浓集系数在10²～10⁴,鱼类胃肠与贝类肉中可达10⁴.水产食品烹饪加工过程²²⁶Ra、²²⁸Ra和²¹⁰Pb在食物链中转移不明显, 经配对显着性检验, 差异无显着性(P0.05);然而210Po在淡水鱼类和虾类中转移是明显的, 肉配对检验有非常显着性差别(P<0.01).结论水生物对²²⁶Ra、²²⁸Ra、²¹⁰Pb和²¹⁰Po有很强浓集能力。     

Rapid determination of Sr impurities in freshly “generator eluted” Y for radiopharmaceutical preparation

⁹⁰Y is one of the most useful radionuclides for radioimmunotherapeutic applications and has a half-life (t_1/2=64.14 h) suitable for most therapeutic applications, beta particles of high energy and decays to a stable daughter. It is significant that ⁹⁰Y is available conveniently and inexpensively from a radionuclide “generator” by decay of its parent, ⁹⁰Sr. Nevertheless, current and planned clinical applications with [⁹⁰Y] labelled compounds employ activity levels that cannot be readily obtained from an in-house generator, but from commercial sources. We have evaluated Eichrom's Sr-resin, either as an “in-house” generator or as a fast QC method for analysis of ⁹⁰Y solutions.In particular, for the development as a generator, we investigated the percentage of the radio-Sr in the first 8 M HNO₃ eluate: in this fraction the concentration of ⁹⁰Sr must be smaller than 10⁻⁵% (recommendations of the International Commission on Radiological Protection). For evaluation as a rapid QC method, we analyzed the concentration of ⁹⁰Y in all the fractions containing “only” radio-Sr: ⁹⁰Y should not be present in these eluates. After the collection of β⁻ and γ spectra and analysis of them, we concluded that commercial Sr-resin minicolumn cannot give us the results expected; we developed an in-house system loaded with 4 mL of Sr-resin which gave better results as a generator and a rapid QC method.     

Production of large quantities of 90Y by ion-exchange chromatography using an organic resin and a chelating agent

The performance of a system composed of an organic cation exchanger (Dowex 50Wx8) and a chelating agent (EDTA) previously described for the successful production of (90)Y via a (90)Sr/(90)Y generator is assessed under dynamic conditions. In an attempt to overcome the established limitation of ion-exchange resins for the separation of subcurie quantities of activity, (90)Y is repeatedly isolated from an 11.8-GBq (320 mCi) (90)Sr cow using a three-column tandem arrangement. The high recovery and radionuclidic purity obtained for (90)Y and the parameters of the separation (time, eluant concentration, pH and flow rate range) strongly suggest that Ci quantities of (90)Y can be handled satisfactorily by the ion-exchange method. No replacement or treatment of the cow, low waste generation and (90)Sr losses less than 0.1% after each run were observed during the present study which, in combination with the low cost of this resin, may result in an attractive alternate method for the production of large quantities of (90)Y.     

Radiobiological Issues in the Anomalous Enhanced Effect of Low-dose-rate Fission-spectrum Neutrons: Reply to Letter to the Editor by G. W. Barendsen

Summary

The influence of diet or its ingredients on ¹⁴¹Ce absorption and retention was investigated in six-day-old rats. Animals were fed over 8 h with cow's milk, rat diet or a mixture of rat diet ingredients (fish meal, sunfiower meal, alfalfa, cane molasses and premix) labelled with ¹⁴¹Ce. Whole-body radioactivity was determined in a double crystal scintillation counter every 24 h over a six-day period. Gut, liver, kidney and femur retention and cerium distribution in the gut was determined at the end of the experiment. Compared to milk diet, administration of rat diet or ingredients caused respectively 3 and 7·5 times lower whole body retention. Carcass retention was reduced by rat diet or ingredients 2–3 times and intestinal retention 3 and 8 times respectively. Irrespective of the dietary treatment the main site of cerium intestinal retention was the ileum. Our present results indicate that some compounds of rat diet might be considered as a means of reducing cerium absorption and intestinal retention in the very young.     

Comparison of [18F]FDG-PET and L-3[123I]-iodo-alpha-methyl tyrosine (I-123 IMT)-SPECT in primary lung cancer

OBJECTIVE: The aim of this study was to evaluate L-3[123I]-iodo-alpha-methyl tyrosine (IMT)-SPECT and FDG-PET in pulmonary lesions suspected to be lung cancer. METHODS: Whole body PET (measured transmission corrected emission scans) was performed 45 minutes after i.v. injection of 222-370 MBq (6-10 mCi) 18F-FDG on a Siemens PET scanner (ECAT EXACT 47) including 5-6 bed positions. 123I-IMT-SPECT (chest) was performed after injection of 370 MBq (10 mCi) with a dual head camera (Picker Prism 2000) and commercially available reconstruction algorithms. Ten patients (6 male and 4 female) with suspected lung cancer were investigated. The results were compared to histological findings after surgery or bronchoscopic biopsies and CT. RESULTS: 123I-IMT-SPECT and FDG-PET were able to detect all 9 cases of lung cancer (1-8 cm in diameter). One case was true negative. Both imaging methods were true positive with respect to mediastinal lymph node metastases in one patient. The tumor/background ratio was higher with PET (8.20 vs. 2.84). CONCLUSION: Despite the limited number of patients it may be concluded that IMT-SPECT as well as FDG-PET are suited to correctly diagnose lung cancer. Nevertheless, FDG-PET, if available, seems to be better suited because of the higher tumor/background ratio and better resolution.     

Pre-therapeutic dosimetry and biodistribution of 86Y-DOTA-Phe1-Tyr3-octreotide versus 111In-pentetreotide in patients with advanced neuroendocrine tumours

Purpose For the internal radiotherapy of neuroendocrine tumours, the somatostatin analogue DOTATOC labelled with ⁹⁰Y is frequently used [⁹⁰Y-DOTA-Phe¹-Tyr³-octreotide (SMT487-OctreoTher)]. Radiation exposure to the kidneys is critical in this therapy as it may result in renal failure. The aim of this study was to compare cumulative organ and tumour doses based upon dosimetric data acquired with the chemically identical ⁸⁶Y-DOTA-Phe¹-Tyr³-octreotide (considered as the gold standard) and the commercially available ¹¹¹In-pentetreotide.Methods The cumulative organ and tumour doses for the therapeutic administration of 13.32 GBq ⁹⁰Y-DOTA-Phe¹-Tyr³-octreotide (three cycles, each of 4.44 GBq) were estimated based on the MIRD concept (MIRDOSE 3.1 and IMEDOSE). Patients with a cumulative kidney dose exceeding 27 Gy had to be excluded from subsequent therapy with ⁹⁰Y-DOTA-Phe¹-Tyr³-octreotide, in accordance with the directives of the German radiation protection authorities.Results The range of doses (mGy/MBq ⁹⁰Y-DOTA-Phe¹-Tyr³-octreotide) for kidneys, spleen, liver and tumour masses was 0.6–2.8, 1.5–4.2, 0.3–1.3 and 2.1–29.5 (⁸⁶Y-DOTA-Phe¹-Tyr³-octreotide), respectively, versus 1.3–3.0, 1.8–4.4, 0.2–0.8 and 1.4–19.7 (¹¹¹In-pentetreotide), with wide inter-subject variability. Despite renal protection with amino acid infusions, estimated cumulative kidney doses in two patients exceeded 27 Gy.Conclusion Compared with ⁸⁶Y-DOTA-Phe¹-Tyr³-octreotide, dosimetry with ¹¹¹In-pentetreotide overestimated doses to kidneys and spleen, whereas the radiation dose to the tumour-free liver was underestimated. However, both dosimetric approaches detected the two patients with an exceptionally high radiation burden to the kidneys that carried a potential risk of renal failure following radionuclide therapy.     

Comparison of extraarticular leakage values of radiopharmaceuticals used for radionuclide synovectomy

OBJECTIVES: Radionuclide synovectomy is a reliable therapy in patients with chronic synovitis. However, radiation doses delivered to non-target organ systems due to leakage of radioactive material from the articular cavity are an important disadvantage of this procedure. In this study we compared extraarticular leakage values of the 3 commonly used radiopharmaceuticals; 90Y-citrate, 90Y-silicate and 186Re-sulfide colloid. MATERIALS AND METHODS: Thirty-five patients with persistent synovitis were enrolled in the study. Twenty-two hemophilic, 8 rheumatoid arthritis and 5 patients with pigmented villonodular synovitis were studied. 90Y labeled silicate and citrate were used for knee joints and 186Re-sulfide for intermediate sized joints. Radiocolloid leakage values were evaluated using a gamma camera with 20% window centered over the bremsstrahlung photopeak of 90Y and a respective window over the 137 keV photopeak of 186Re. Regions of interest were drawn over the injection site, the regional lymph nodes and the background areas. Leakage of radiocolloid was calculated by dividing the counts/pixel in the regional lymph node area to the counts/pixel in the injection site. RESULTS: No visible leakage was observed. The median leakage values calculated for 90Y-citrate, 90Y-silicate and 186Re-sulfide were found as 1.9%, 2.4% and 2.7%, respectively. The difference between the variability of leakage values was not statistically significant (p > 0.05). CONCLUSION: There was no significant difference in terms of extraarticular leakage between 9Y-citrate, 9Y-silicate and 186Re-sulfide radiocolloids.     

Rapid synthesis and in vitro and in vivo evaluation of folic acid derivatives labeled with fluorine-18 for PET imaging of folate receptor-positive tumors

In an attempt to visualize folate receptors that overexpress on many cancers, [¹⁸F]-fluorobenzene and pyridinecarbohydrazide-folate/methotrexate conjugates ([¹⁸F]-1, [¹⁸F]-2-folates and [¹⁸F]-8, [¹⁸F]-9-MTXs) were synthesized by the nucleophilic displacement reactions using ethyl-trimethylammonium-benzoate and pyridinecarboxylate precursors. The intermediates ethyl [¹⁸F]-fluorinated benzene and pyridine esters were reacted with hydrazine to produce the [¹⁸F]-fluorobenzene and pyridinecarbohydrazides, followed by coupling with N-hydroxysuccinimide-folate/MTX. Radiochemical yields were greater than 80% (decay corrected), with total synthesis time of less than 45 min. Radiochemical purities were always greater than 97% without high-performance liquid chromatography purification. These synthetic approaches hold considerable promise as rapid and simple method for the radiofluorination of folate derivatives with high radiochemical yield in short synthesis time. In vitro tests on KB cell line showed that significant amount of the radioconjugates were associated with cell fractions, and in vivo characterization in normal Balb/c mice revealed rapid blood clearance of these radioconjugates with excretion predominantly by the urinary and partially by the hepatobiliary systems. Biodistribution studies in nude mice bearing human KB cell line xenografts demonstrated significant tumor uptake and favorable biodistribution profile for [¹⁸F]-2-folate over the other conjugates. The uptake in the tumors was blocked by excess coinjection of folic acid, suggesting a receptor-mediated process. Micro-positron emission tomography images of nude mice bearing human KB cell line xenografts confirmed these observations. These results demonstrate that [¹⁸F]-2-folate may be useful as molecular probe for detecting and staging of folate receptor-positive cancers, such as ovarian cancer and their metastasis as well as monitoring tumor response to treatment.     

Repeated 0.5-Gy γ-ray irradiation attenuates autoimmune manifestations in MRL-lpr/lpr mice

Purpose: MRL-lpr/lpr mice, a model for various autoimmune diseases, were repeatedly irradiated with 0.5 Gy of γ-rays, and changes in their autoimmune manifestations were investigated.

Materials and methods: MRL-lpr/lpr mice at 13 weeks of age were maintained in plastic cages and exposed whole-body to 0.5 Gy γ-ray irradiation from a ¹³⁷Cs source 5 times per week for 4 weeks, from the time they were 13 weeks old until they reached 17 weeks old. Changes of autoimmune manifestations were examined 3 weeks later at the 20th week.

Results: Splenomegaly, lymphadenopathy, and proteinuria in MRL-lpr/lpr mice were clearly ameliorated by a total dose of 10 Gy (0.5 Gy/day×5 days/week for 4 weeks). Histologically severe disease-specific damage to the kidney and the salivary gland, i.e., glomerulonephritis and sialoadenitis, was also improved after irradiation. CD3⁺ CD4^? CD8^? CD45R/B220⁺ T cell numbers, which proliferate abnormally in MRL-lpr/lpr mice, were significantly decreased by the irradiation, possibly through induction of apoptosis. The elevated NO₂^? and NO₃^? (NO_x^?) production by macrophages of MRL-lpr/lpr mice was lowered by the irradiation. The irradiation also prolonged the life span of MRL-lpr/lpr mice. These phenomena may contribute to the amelioration of autoimmune manifestations in MRL-lpr/lpr mice exposed to repeated small-doses of γ-rays.

Conclusions: Repeated small-dose γ-ray exposure ameliorates the autoimmune manifestations in MRL-lpr/lpr model mice.