125Ⅰ粒子近距离治疗前列腺癌临床应用

目的探讨经会阴超声引导放射性125Ⅰ粒子近距离治疗前列腺癌的近期疗效和并发症.方法32例前列腺癌患者实施经会阴超声引导放射性125Ⅰ粒子植入术,11例单纯粒子治疗,6例术前或术后配合外放疗.15例粒子植入术后加睾丸去势术.连续3次前列腺特异抗原(prostatespecific antigen,PSA)升高即为生物化学失败.结果14例原发前列腺癌粒子植入治疗前和治疗后血清PSA分别为(52.14±54.61)ng/ml和(4.26±7.11)ng/ml,统计学处理差异有显著性(t=3.253,P=0.003),生物化学控制率为100%.12例去势术后复发患者125Ⅰ粒子植入治疗前和治疗后PSA分别为(15.14±20.80)ng/ml和(18.94±35.25)ng/ml(t=-0.307,P=0.764),统计学处理差异无显著性,生物化学控制率为75%.5例骨转移患者术前和术后PSA分别为(120.03±145.96)ng/ml和(75.53±84.84)ng/ml(t=0.527,P=0.621),统计学处理差异无显著性.125Ⅰ粒子单纯植入治疗34.62%患者无尿道副反应,Ⅰ～Ⅴ级尿道副反应发生率分别为38.46%、11.54%、11.54%、0和3.85%.125Ⅰ粒子植入联合外放疗组Ⅰ～Ⅳ级副反应发生率分别为16.67%、0、0和16.67%.Ⅰ级直肠副反应发生率为3.12%.3.12%患者1颗粒子移位,没有引起临床相关并发症,无粒子移位到肺.结论超声引导经会阴放射性125Ⅰ粒子植入治疗前列腺癌具有安全、微创、并发症发生率低等优点.     

~(125)I粒子近距离治疗前列腺癌临床应用

目的　探讨经会阴超声引导放射性1 2 5I粒子近距离治疗前列腺癌的近期疗效和并发症。方法　 32例前列腺癌患者实施经会阴超声引导放射性1 2 5I粒子植入术 ,11例单纯粒子治疗 ,6例术前或术后配合外放疗。 15例粒子植入术后加睾丸去势术。连续 3次前列腺特异抗原 (prostatespecificantigen ,PSA)升高即为生物化学失败。结果　 14例原发前列腺癌粒子植入治疗前和治疗后血清PSA分别为 (5 2 14± 5 4 6 1)ng ml和 (4 2 6± 7 11)ng ml,统计学处理差异有显著性 (t=3 2 5 3,P =0 0 0 3) ,生物化学控制率为 10 0 %。 12例去势术后复发患者1 2 5I粒子植入治疗前和治疗后PSA分别为 (15 14± 2 0 80 )ng ml和 (18 94± 35 2 5 )ng ml(t=- 0 30 7,P =0 76 4 ) ,统计学处理差异无显著性 ,生物化学控制率为 75 %。 5例骨转移患者术前和术后PSA分别为 (12 0 0 3± 14 5 96 )ng ml和(75 5 3± 84 84 )ng ml(t =0 5 2 7,P =0 6 2 1) ,统计学处理差异无显著性。1 2 5I粒子单纯植入治疗34 6 2 %患者无尿道副反应 ,Ⅰ～Ⅴ级尿道副反应发生率分别为 38 4 6 %、11 5 4 %、11 5 4 %、0和3 85 %。1 2 5I粒子植入联合外放疗组Ⅰ～Ⅳ级副反应发生率分别为 16 6 7%、0、0和 16 6 7%。Ⅰ级直肠副反应发生率为 3 12 %     

超声引导125I粒子治疗前列腺癌引起的直肠并发症

目的探讨经会阴超声引导放射性^125I粒子近距离治疗前列腺癌的直肠并发症。方法80例前列腺癌患者实施经会阴超声引导放射性^125I粒子植入术，其中68例单纯粒子植入治疗，12例行粒子治疗联合外放疗。单纯^125I粒子治疗肿瘤匹配周边剂量（matched peripheral dose，MPD）为140～160Gy，联合组^125I粒子植入MPD为90～110Gy。联合组外照射剂量为40～50Gy/4～5周，20Gy/次，5次/周，4野照射，粒子植入后4周进行。根据术中计划，利用Mick枪后退式植入粒子，活度为0．35～0．50mCi，中位植入粒子65颗（平均19～100颗）。术后1个月行盆腔CT扫描，进行质量验证。结果68例单纯放射性^125I粒子植入治疗前列腺癌后直肠Ⅰ级、Ⅱ级、Ⅲ级和Ⅳ级副反应发生率分别为7．3％、4．4％、2．9％和1．5％，而12例^125I粒子植入治疗和联合外放疗直肠副反应Ⅰ级和Ⅱ级发生率分别为10％和10％，没有Ⅲ级以上直肠副反应。直肠反应出现中位时间12月（1～16个月）。结论超声引导经会阴放射性^125I粒子植入治疗前列腺癌直肠并发症发生率可以接受，需要进一步明确直肠剂量与发生副反应的关系。     

超声引导下~(125)I粒子植入治疗前列腺癌术后血清PSA变化与疗效评估

目的探讨经直肠超声引导下~(125)I放射性粒子植入治疗前列腺癌患者术后PSA变化及影响治疗效果的危险因素。方法 2010年1月~2015年12月经直肠超声引导下~(125)I放射性粒子植入治疗的前列腺癌患者70例,年龄52~81岁,平均(67.2±0.7)岁,术前均经病理证实为前列腺癌。术前PSA 5.68~35.43ng/ml,平均(14.42±0.73)ng/ml,临床分期T1c~T2b,Gleason评分4~7分,随访3~60个月,依随访结果分三组:A组:良性反弹组,32例(45.7%),B组:生化复发组,12例(17.1%)。C组:疗效稳定组,26例(37.1%)。结果 A组PSA降至最低值后开始升高时间发生在术后(16.5±1.3)月,且65.6%(21/32)出现于14~27周;B组PSA降至最低值后开始升高时间发生在术后(29.7±2.2)月;C组PSA降至最低值时后长期保持稳定。治疗时患者年龄是良性反弹(A组)的危险因素(P=0.0025,P0.01)。A组和B组在PSA降至最低值开始升高时间参数中差异具有统计学意义(P0.01)。结论超声引导下~(125)I放射性粒子植入治疗前列腺癌术后监测血PSA变化有助于临床对治疗效果的评估。     

060经会阴植入125I粒子近距离治疗局限性前列腺癌

从1985～1996年,在阿姆斯特丹学术医疗中心,102例T1～T2N0期前列腺癌患者接受了经会阴植入125I粒子近距离治疗,其中T1c期4例,T2a期73例,T2b期25例.放疗前PSA平均17ng/ml.直肠超声引导下植入放射性粒子,前列腺平均容量31ml(15～48ml),平均植入49粒(29～74).前列腺周边剂量160Gy.直到1988年才有27例追加盆腔外照射40Gy,20d,2Gy/d.     

经会阴植入~(125)I粒子近距离治疗局限性前列腺癌

从1985～1996年,在阿姆斯特丹学术医疗中心,102例T_1～T_2N_0期前列腺癌患者接受了经会阴植入~(125)I粒子近距离治疗,其中T_(1c)期4例,T_(2a)期73例,T_(2b)期25例。放疗前PSA平均17ng/ml。直肠超声引导下植入放射性粒子,前列腺平均容量31ml(15～48ml),平均植入49粒(29～74)。前列腺周边剂量160Gy。直到1988年才有27例追加盆腔外照射40Gy,20d,2Gy/d。结果:5年实际生存率77％,7年实际生存率63％。平均102个月。其中10人(9.5％)死于前列腺癌。5年、7年临床进展率分别为12％、17％。生化指标PSA显示5年、7年失败率分     

前列腺癌ADC值与PSA浓度的相关性研究

目的:探讨前列腺癌表观扩散系数(ADC)值与前列腺特异性抗原(PSA)浓度的相关性。方法:回顾性分析经穿刺活检、手术病理证实的36例前列腺癌患者的临床及影像资料,记录前列腺癌兴趣区的ADC值,测量患者PSA浓度,统计分析各期(TNM分期)前列腺癌病灶ADC值与PSA的相关性。结果:T2期22例,平均ADC值为(0.70±0.08)×10-3 mm2/s,平均PSA值为(70.0±10.7)ng/ml;T3期6例,平均ADC值为(0.76±0.09)×10-3 mm2/s,平均PSA值为(301.0±20.1)ng/ml;T4期8例,平均ADC值为(0.72±0.08)×10-3 mm2/s,平均PSA值为(360.0±25.1)ng/ml。ADC值与PSA浓度在前列腺各期中均存在负相关关系,r值分别为-0.638、-0.674和-0.731,P值均<0.01。结论:前列腺癌病灶的ADC值与PSA浓度呈负相关,根据ADC值可对前列腺癌的生物学特性进行初步评估,可为临床制定合适的治疗方案提供相关信息。     

125Ⅰ粒子源近距离治疗前列腺癌模型的剂量学研究

目的 研究放射性125Ⅰ粒子源在治疗前列腺癌中的剂量分布,探寻治疗计划系统(TPS)优化效果的有效方法.方法 选定1个治疗计划系统,应用热释光剂量计,基于前列腺癌等效模体,模拟测量前列腺癌中的剂量分布.模拟植入共89颗125Ⅰ粒子,每个粒子的活度为1.37×107Bq(±5%).结果 各层的最大剂量为151～241 G...     

MRI在三维适形125I近距离放射治疗前列腺癌的应用

目的 探讨MRI在三维适形¹²⁵I近距离放射治疗对于非转移性去势抵抗性前列腺癌(nonmetastatic castration-resistant prostate cancer, nCRPC)治疗前的应用价值。方法 选取13例接受¹²⁵I放射性粒子永久性近距离挽救性放疗的nCRPC患者，治疗前行MRI检查，分析MRI影像特征。结果 前列腺癌Gleason评分(7.08±0.95)分，术前PSA平均(6.27±4.37) ng/ml。PSA升至术前水平时间(11.1±3.9)个月；PSA上升至术前水平的时间与术前PSA呈负的直线相关关系。所有患者无尿潴留、放射性膀胱炎、放射性直肠炎、尿道狭窄等并发症；患者住院时间平均为(5.6±1.5)天，术后住院(1.8±0.8)天。结论 MRI检查在三维适形¹²⁵I近距离放射治疗对于非转移去势抵抗性前列腺癌治疗前的效果良好，PSA上升至术前水平的时间与术前PSA呈负的直线相关关系。     

125I粒子植入治疗结肠直肠癌肝转移

目的 探讨放射性125I粒子植入治疗结肠直肠癌肝转移(CRLM)的疗效及安全性.方法 为24例化疗失败或不能耐受化疗的CRLM患者共计65个肝转病灶行CT引导下植入125I粒子,粒子的放射性活度介于0.5 ～ 0.7 mCi,每例患者接种的粒子数为18 ～ 109枚,最小边缘剂量为110 ～ 160 Gy.植入后进行质量验证.结果 在6个月的随访中,肿瘤的最长径基线和从术前(7.21±3.28) cm降到术后3个月时的(4.47±3.34)和6个月时的(3.94±2.05) cm,差异有统计学意义(P＜0.05).CEA由术前的(293±89) ng/ml降至术后3、6个月的(198±103)ng/ml、(155±61) ng/ml,差异有统计学意义(P＜0.05).未出现与治疗相关的死亡.1、2年生存率分别为87.5％和75.0％.结论 CT引导下125I粒子植入治疗CRLM微创、安全,近期疗效确切,远期疗效有待观察.     

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.     

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 [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.     

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.