手术联合125Ⅰ放射性粒子植入治疗下颌下腺腺源性恶性肿瘤

目的 对手术联合¹²⁵Ⅰ放射性粒子植入治疗下颌下腺腺源性恶性肿瘤进行临床初步研究。方法 选取2005年12月至2012年12月就诊于北京大学口腔医学院的下颌下腺腺源性恶性肿瘤患者32例,所有患者均行肿物及下颌下腺切除,临床及影像学检查未见淋巴结转移,未行扩大切除术或颈部淋巴结清除术。手术后结合手术前CT检查所见、肿瘤位置、大小及手术后病理学分型确定靶区,处方剂量90~110 Gy。全麻下按治疗计划将 ¹²⁵Ⅰ放射性粒子植入靶区。术后定期随访,观察临床疗效及并发症,计算局部-颈部控制率和远处转移率、生存率。结果 32例患者植入 ¹²⁵Ⅰ放射性粒子1 394颗,人均43颗,术后验证D₉₀和V₁₀₀均满足治疗需要,周围重要器官如舌、颌骨、脊髓均在耐受剂量以内。随访15~126个月,平均随访64个月,5例局部复发,5例远处转移,4例死亡。3年和5年的局部-颈部控制率分别为93.1%和87.9%,总生存率分别为93.3%和84.5%。未发现张口受限、放射性龋齿、放射性颌骨骨髓炎等并发症。结论 下颌下腺腺源性恶性肿瘤行手术切除肿物及下颌下腺,术后联合 ¹²⁵Ⅰ放射性粒子植入治疗,临床疗效良好,并发症小。     

125I粒子植入联合内分泌治疗前列腺癌疗效观察

目的 回顾性分析¹²⁵I粒子植入联合内分泌治疗T₃N₀M₀期前列腺癌的疗效和不良反应。方法 临床分期为T₃N₀M₀前列腺癌患者22例,行经直肠超声引导¹²⁵I粒子植入联合内分泌治疗。靶区最小周边剂量为140~160 Gy,尿道剂量<400 Gy。中位粒子数74颗(26~90颗),中位粒子活度1.55×10⁷ Bq(1.30×10⁷~1.85×10⁷)Bq。11例行去势手术,11例行药物去势联合抗雄激素治疗。结果 22例患者均顺利完成粒子植入治疗。5年无生化失败生存率为70.6%,总生存率为81.8%。2例于粒子植入术后12个月出现生化失败,1例在术后90个月出现生化失败,重新给予内分泌治疗。粒子植入治疗后1级、2级尿道不良反应发生率分别为54.5%、9.1%,1级和2直肠不良反应发生率分别为22.7%和9.1%,1例出现4级直肠反应。结论 放射性¹²⁵I粒子植入联合内分泌治疗T₃N₀M₀期前列腺癌创伤小、疗效好,可以考虑应用于不愿接受外放疗的患者。     

60Coγ射线诱导人淋巴细胞线粒体COX基因表达改变的研究

目的 探讨电离辐射诱导人淋巴细胞线粒体COXⅠ、COXⅡ和COXⅢ基因表达的改变。方法 用1、3、5、8和10 Gy ⁶⁰Co γ射线分别照射指数增长期的人淋巴细胞永生化细胞株,8 h后用逆转录PCR(RT-PCR)和实时荧光定量PCR(Real-time PCR)方法检测COXⅠ、COXⅡ和COXⅢ基因在mRNA水平上的表达;流式细胞术检测其在蛋白水平上的表达;比色法检测COX活性,来分析辐射诱导线粒体COXⅠ、COXⅡ和COXⅢ基因表达改变的量效关系。同时,以5 Gy γ射线照射人淋巴细胞,分别于照后不同时间(0.5、4、8、12、24、48和72 h),同样通过上述指标来分析3种线粒体基因的表达变化,观察其时效关系。 结果 在mRNA水平上,线粒体COXⅠ、COXⅡ和COXⅢ基因表达总体上调。COXⅠ和COXⅢ基因在0～3 Gy剂量范围内具有量效关系,而COXⅡ基因在0～8 Gy剂量范围内具有量效关系(F_COXⅠ=116.62,F_COXⅡ=17.89,F_COXⅢ=8.20,P<0.05);5 Gy 照后4 h左右COXⅡ和COXⅢ基因表达上调最显著,而COXⅠ基因持续低表达(F _COXⅠ=31.99,F_COXⅡ=19.47,F_COXⅢ=20.64,P<0.05)。在蛋白水平上,不同剂量照射后,COXⅠ和COXⅡ蛋白表达先下调后上调,COXⅢ蛋白表达下调(F_COXⅠ=16.96,F_COXⅡ=32.5,F_COXⅢ=6.51,P<0.05);5 Gy照后4 h,COXⅠ蛋白表达明显增强,达到8 h后出现COXⅡ蛋白表达显著上调,而COXⅢ蛋白表达普遍下调(F_COXⅠ=14.68,F_COXⅡ=17.18,F_COXⅢ=2.52,P<0.05)。此外, 受照后COX活性普遍降低。结论 电离辐射可以诱导人淋巴细胞线粒体COXⅠ、COXⅡ和COXⅢ基因表达的改变,基因表达总体增强的同时,COX活性普遍降低。     

腮腺癌术后 125I 粒子组织间近距离治疗靶区确定方法的探讨

目的 探讨腮腺癌术后¹²⁵I粒子组织间近距离治疗靶区的确定方法。方法 2002年10月至2006年11月北京大学口腔医院的31例腮腺癌患者,男女比例14 ∶17,平均年龄38.2岁,肿瘤有包膜外浸润并与面神经关系密切(黏连或神经侵犯),采用保留面神经的肿瘤及腺体切除术,术后行¹²⁵I粒子组织间近距离治疗,匹配周缘剂量60 Gy。治疗前后行薄层螺旋CT扫描以制定治疗计划和质量验证,以腮腺周围骨性结构和肌组织为参照确定计划靶区和临床靶区,并比较治疗前后靶体积、靶区D₉₀值的差异,同时计算粒子植入后颌骨、中耳D₉₀值以及脊髓最大接受剂量。结果 ¹²⁵I粒子治疗前后靶体积、靶区D₉₀值差异无统计学意义,粒子植入后靶区D₉₀值均大于匹配周缘剂量。本组病例随访时间3~7年,未见肿瘤复发。结论 根据目前随访结果,采用本方法确定¹²⁵I粒子腮腺区组织间近距离治疗靶区,临床治疗效果满意。     

鼻咽癌常规和超分割后加速放疗的疗效分析

目的 比较鼻咽癌常规和超分割后加速放疗的局部控制率和生存率。 方法 200例初治鼻咽癌患者根据计算机产生的随机数入常规组和超分割后加速放疗组,鼻咽原发灶采用⁶⁰Co γ射线或6 MV X射线外照射,常规组70 Gy/35次/7周,超分割后加速放疗组前4周采用超分割1.2 Gy/次,剂量为48 Gy/40次,后2周加速超分割1.5 Gy/次,剂量为30 Gy/20次,均为2次/d,间隔≥6 h,5 d/周。结果 常规组99例中,远处转移25例、鼻咽复发25例、颈部复发16例;超分割后加速放疗组101例中,远处转移18例、鼻咽复发16例、颈部复发13例。常规组和超分割后加速组5年鼻咽局部控制率分别为75.9%、87.6% (χ²=4.066, P<0.05),总生存率分别为58.0%、74.1%(χ²=5.076, P<0.05),5年无远处转移率分别为74.1%、83.3%(P> 0.05),颈部局部控制率分别为81.5%、90.0%(P> 0.05)。结论 与常规分割相比,超分割后加速放疗组提高了鼻咽局部控制率和总生存率,未减少颈部复发和远处转移率。     

基于蒙特卡罗模拟的9 C重离子衰变产物对细胞损伤的分析

目的 探究⁹C重离子治疗中因自身衰变产生的缓发粒子对细胞产生的辐射损伤和在单个V79中国仓鼠肺细胞模型上的微观剂量以及引起的生物学效应。方法 采用蒙特卡罗程序模拟多种能量(3~10 MeV)α粒子在细胞(细胞半径R_C=10 μm,细胞核半径R_N=5 μm)中的输运后细胞核内吸收剂量结果,并与医学内照射剂量(MIRD)方法S值(S_N←N,S_N←Cy,S_N←CS)进行比较,证明该方法的可行性,最后使用蒙特卡罗方法模拟计算⁹C重离子分别在V79细胞模型表面、细胞质内以及细胞核3种位置处衰变生成的缓发粒子(α粒子和质子)在靶中输运能量沉积情况及细胞生存率。结果 蒙特卡罗模拟结果与MIRD方法S值进行比较,靶源组合从细胞核到细胞核S_N←N值的差异为1.91%~4.95%,细胞质到细胞核S_N←Cy为1.48%~5.11%,细胞表面到细胞核S_N←CS差异为-1.99%~0.80%,证明蒙特卡罗计算值与MIRD方法S值吻合较好(差异值均< 6%)。当一个⁹C离子在V79细胞模型表面衰变产生次级粒子进入细胞,细胞核内平均吸收剂量为10^-2Gy数量级,计算细胞生存率约为88%;衰变在细胞质中进行,计算细胞生存率约为80%;当碳离子直接进入细胞核中衰变,α粒子射程短并将大部分能量沉积在细胞中(细胞核内平均剂量0.1 Gy数量级),造成细胞损伤较大,细胞存活的概率约为53%。结论 ⁹C离子自身衰变发射次级带电粒子,其中α粒子进入细胞核时对细胞造成的损伤较大,生物学效应明显。     

个体化模板辅助颅底区永久性组织间近距离治疗的可行性研究

目的 评价个体化模板辅助技术在颅底区恶性肿瘤永久性组织间近距离治疗中应用的可行性。方法 选择2010年8月至2012年6月在北京大学口腔医院口腔颌面外科接受¹²⁵I粒子永久性植入治疗的颅底区复发性恶性肿瘤患者20例。植入前行头颈部CT扫描获得Dicom数据,导入组织间近距离治疗计划系统进行预计划和模拟针道设计,然后将含有模拟针道信息的图像文件导入Mimics软件和Geomagic软件进行个体化模板数字建模,最后利用医用光敏树脂经快速成型技术制作个体化模板。粒子植入过程中,应用个体化模板控制针的插植和粒子的植入,并CT扫描验证插植针空间位置分布。粒子植入后CT扫描进行粒子空间分布和实际剂量验证。粒子植入过程中和植入后72 h内观察并记录并发症。结果 20例颅底区复发恶性肿瘤患者应用个体化模板技术,均顺利完成了¹²⁵I粒子植入。个体化模板同时具有预计划插植针道信息和患者面部特征信息,插植针定位和定向准确。¹²⁵I粒子平均植入70颗(20～172颗),空间分布均匀,无移位和脱落。粒子平均活度0.7 mCi/颗(0.6～0.8 mCi/颗, 1 Ci=3.7×10¹⁰ Bq),平均D₉₀=181.6 Gy(127.4～279.6 Gy),平均V₁₀₀为98.2%(94.6%～100%),平均V₁₅₀为43.2%(24.3%～52.2%),危及器官的平均受照剂量为31.6 Gy(24.6～47.3 Gy)。未观察到严重并发症。结论 应用个体化模板辅助颅底区永久性组织间近距离治疗,方法安全可行,具有插植针定位、定向准确的特点,可明显提高治疗的精确性,避免插植操作的盲目性。     

60Co γ射线诱发小鼠外周血网织红细胞微核率的研究

目的 通过观察不同剂量⁶⁰Co γ射线照射后小鼠外周血网织红细胞微核率的变化,为使外周血网织红细胞微核成为探索快速高通量的生物剂量计提供科学依据。方法 ⁶⁰Co γ射线照射ICR小鼠,按不同照射剂量分为0、0.5、1、2、4和8 Gy组,眼球取血,流式细胞术(FCM)检测和显微镜观察小鼠外周血网织红细胞微核率的变化。结果 流式细胞术检测网织红细胞微核率随剂量增加逐渐增加,2 Gy达峰值,之后随剂量的增加而减少;显微镜观察的网织红细胞微核率变化趋势与流式细胞术检测结果基本一致。照射剂量在0~2 Gy剂量范围内,小鼠的外周血网织红细胞微核率的剂量-效应关系满足直线模型(R²=0.9063),并且2 Gy照射组与0 Gy组相比差异有统计学意义(t=-2.856,P<0.05)。结论 流式细胞术检测外周血网织红细胞微核率,在一定剂量范围内可成为早期快速、高通量的辐射损伤生物剂量计。     

调强放疗联合顺铂治疗宫颈癌的临床观察

目的 观察宫颈癌患者调强放疗（IMRT）联合顺铂治疗疗效及不良反应。方法 回顾性分析100例宫颈癌患者,按治疗方法不同分为单纯治疗组和联合治疗组,每组各50例,均给予IMRT外照射,总剂量为50 Gy,2 Gy/次,共25次,5次/周;外照射2周时开始行内照射,1次/周,6~7 Gy/次,共6~8次,总剂量为42~48 Gy。联合治疗组加顺铂同步化疗,静脉滴注,1次/周,30~40 mg/m²,连用4~5周。观察近期疗效和1、3、5年生存率,局部控制率、远处转移率和无瘤生存率,并评价两组患者的不良反应。结果 联合治疗组与单纯治疗组比较,近期疗效及1年生存率,局部控制率、远处转移率、无瘤生存率无明显差异,联合治疗组的3年与5年生存率、局部控制率、远处转移率、无瘤生存率均优于单纯治疗组（χ²=3.843、4.336、4.336、4.960,P<0.05;χ²=3.934、4.454、4.000、4.244, P<0.05）。联合治疗组放射性直肠炎、白细胞总反应率高于单纯治疗组（χ²=4.110、4.320,P<0.05）,两组膀胱炎、贫血、血小板总反应率比较无差异,均未出现3~4级直肠炎和膀胱炎。结论 IMRT联合顺铂同步化疗治疗宫颈癌比单纯IMRT疗效好。     

Ⅲa-pN2非小细胞肺癌术后同步放化疗与单纯化疗随机对照研究

目的 通过随机对照研究、比较非小细胞肺癌（NSCLC）患者放化疗（POCRT）和单纯化疗（POCT）的疗效。方法 对术后140例病理分期为Ⅲ_a-pN₂的NSCLC患者用随机信封法分为POCRT组和POCT组,每组70例。两组化疗方案均采用紫杉醇和顺铂,共化疗4个周期。在第1、21、43、64天给予紫杉醇175 mg/m²,顺铂60 mg/m²静脉滴注。POCRT组在化疗的第1天给予同期放疗,50.4 Gy/28次。结果 POCRT组5年总生存率为37.9%;POCT组5年总生存率为27.5%,POCRT组死亡风险比为0.69（95%CI,0.457~1.044,χ²=3.224,P>0.05）。POCRT组5年无复发生存率为30.3%;POCT组5年无复发生存率为18.8%,POCT组复发风险比为1.49（95%CI,1.008~2.204,χ²=4.193,P<0.05）。亚组分析显示POCRT组能明显提高pN₂淋巴结≥2枚患者总生存率（χ²=5.308,P<0.05）。POCRT组复发率（χ²=5.308,P<0.05）和远处转移率（χ²=3.840,P<0.05）均显著低于POCT组。POCRT组1例患者死于脓毒血症,POCRT组发生3,4级放射性食管炎高于POCT组（χ²=8.010,P<0.05）,两组血液学毒性相似且可耐受。结论 和POCT相比,POCRT能减少 Ⅲ_a-pN₂的非小细胞肺癌患者的局部复发率和远处转移率,提高无复发生存率,POCRT未能提高总生存率。     

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.