~(131)Ⅰ与~(132)Ⅰ对大鼠甲状腺损伤的形态计量学比较研究

应用图像分析技术和形态计量学方法，测量了１３１Ⅰ、１３２Ⅰ注入后２０月大鼠甲状腺组织损伤体视学参数的变化。结果表明，各剂量组胶体和滤泡的体积密度及表面积密度均明显小于对照组，且随着吸收剂量的增大逐渐减小（Ｐ＜００１）；间质的体积密度则随着剂量的增大而明显增大（Ｐ＜００１）；胶体的半径、体积和表面积随剂量的增大而明显变小；１３１Ⅰ、１３２Ⅰ各剂量组胶体半径的频率或概率分布的峰值均随照射剂量的增大而明显左移，即分布范围变窄，胶体的最大半径Ｘｍａｘ和期望值Ｅ（ｘ）显著变小。上述结果说明，胶体或滤泡的体积变小萎缩。用体积密度、表面积密度、胶体平均半径、体积和表面积等参数与吸收剂量的回归方程式计算出的半减或半增剂量Ｄ５０造成此相同效应１３１Ⅰ所需剂量为１３２Ⅰ的７～２６倍；因而，以１３１Ⅰ作为参考辐射造成此生物终点的１３２Ⅰ的相对生物效应（ＲＢＥ）为７～２６。     

人体乳腺单纯癌癌细胞超微结构的定量研究

应用体视学方法对１０例晚期女性乳腺单纯癌癌细胞线粒体、溶酶体、粗面内质网、核糖体的２８个形态结构参数进行体视学测定和分析。结果发现，癌细胞与正常细胞比较，４种细胞器的有关体积、表面积、面数密度及数密度等１７种形态参数有高度显著和显著差异；线粒体、粗面内质网形态结构均发生了显著变化，核糖体的数目明显增多。上述研究为今后研究不同期乳腺癌癌细胞超微结构的定量变化打下基础，并力求对乳腺癌的分期及病因提供较准确的定量依据。     

缺碘大鼠甲状腺结构及其变化的体视学研究

本文对缺碘饮食喂养１２周大鼠的甲状腺进行了组织学观察，并应用ＭＩＡＳ－３００型图像分析系统对甲状腺滤泡、滤泡腔以及滤泡上皮细胞进行了体视学指标的测量，并与对照组进行了比较分析。结果表明，缺碘组大鼠甲状腺明显肿大，其重量约为对照组的５倍；甲状腺呈弥漫性增生性甲状腺肿改变，表现为小滤泡性增生，上皮细胞增生肥大。体视学参数测量结果表明，缺碘组甲状腺滤泡及滤泡腔的平均体积（Ｖ）和平均表面积（Ｓ）均明显低于对照组；而数密度（Ｎｖ）及比表面（Ｓ／Ｖ）明显高于对照组；体积密度（Ｖｖ）和表面积密度（Ｓｖ）也发生不同程度变化；滤泡上皮细胞的截面积显著大于对照组。上述体视学测量结果以定量数据佐证了缺碘性甲状腺肿的形态学变化     

经LZ－410盼生安作用后肝癌细胞AgNORs的形态计量学改变

本文应用图像分析技术和形态计量学方法，测定了肝癌细胞经ＬＺ－４１０不同剂量处理后，ＡｇＮＯＲｓ形态计量学参数的变化。实验结果表明，经ＬＺ－４１０处理后细胞内ＡｇＮＯＲｓ的平均颗粒数和平均面积随剂量的增加而明显减小，并有较好的量效关系，表明ＬＺ－４１０可能有减弱肝癌细胞增殖能力、降低肝癌细胞恶性程度的作用。上述参数与给药剂量间有明确的函数依赖关系（Ｐ＜００５～Ｐ＜００１）。     

肝癌“双弹头”免疫导向药物的实验研究

以肝细胞癌单克隆抗体ＨＡｂ１８为载体，应用间接交流方法及氯胺Ｔ法，将１３１Ｉ和抗癌药物阿霉素（ＡＤＭ）连接到ＨＡｂ１８上，制备出“双弹头”肝癌免疫导向药物１３１Ｉ─ＨＡｂ１８─ＡＤＭ，其标记率为８５％，比放射性为７．７３×ｌ０４Ｂｑ／μｇ（１．９８μＣｉ／μｇ），免疫结合率为４３．５％。细胞毒实验结果显示，１３１Ｉ─ＨＡｂ１８─ＡＤＭ对靶肿瘤细胞ＳＭＭＣ─７７２１的杀伤效果明显强于ＨＡｂ１８─ＡＤＭ、ＨＡｂ１８─１３１Ｉ、ＡＭＤ。１３１Ｉ─ＨＡｂ１８─ＡＤＭ具有选择性的高效杀伤作用，它集中了化疗与内放射治疗的优点，互相补充，展示了肿瘤导向治疗的光明前景。     

正常人舌脱落上皮细胞的形态计量分析

获取正常人舌脱落细胞中不同细胞的形态计量学参数值及总体细胞形态计量学参数的频率分布图。采集 30例正常人舌脱落上皮细胞 ,涂片后作巴氏染色 ,应用MIPS - 1图像分析系统对脱落细胞进行形态计量学检测。测得了中层细胞、角化前细胞、不全角化细胞、完全角化细胞等不同脱落细胞的面积、周长、形状因子、等效直径和最大直径等形态计量学参数 ;分析了总体脱落细胞面积、形状因子及最大直径 3项参数。获得了正常人舌脱落细胞中不同细胞的形态计量学参数及总体细胞形态计量学参数值的频率分布图。     

双弹头组合单抗免疫导向治疗肝癌的实验研究

以肝癌单克隆抗体ＨＡｂ１８、ＨＡｂ２５为载体，以￣（１３１）Ｉ、阿霉素（ＡＤＭ）为“弹头”．应用间接交联方法及氯胺Ｔ法，制备出肝癌“双弹头组合单抗”免疫导向偶合物［￣（１３１）Ｉ－ＨＡｂ１８－ＡＤＭ］／［￣（１３１）Ｉ－ＨＡｂ２５－ＡＤＭ］，其标记率４９．８％，比放射性６．８８×１０４Ｂｑ／μｇ，免疫结合率４２．５％。细胞毒实验结果显示双弹头组合单抗偶合物杀伤力显著强于单弹头单抗体偶合物（Ｐ＜０．０５）。荷肝癌棵鼠导向治疗实验，１６８小时ＳＰＥＣＴ扫描清楚定位，瘤／肝比值３．７３５±０．１２０，治疗效果显著强于其它各组（Ｐ＜０．０５）。上述结果表明，“双弹头”集中了化疗与放疗优点，二者协同，明显提高了杀伤效应；组合单抗较好地消除了肿瘤异质性对导向治疗的影响。     

氟尿嘧啶对BEL－7402肝癌细胞作用的形态计量学研究

本文应用图像分析和形态计量学的方法研究了ＢＥＬ－７４０２肝癌细胞系经氟尿嘧啶（５－Ｆｕ）作用后细胞及细胞核的１５项形态计量学参数的变化。结果表明细胞及细胞核的面积、周长、最大直径、最小直径、等效直径、等效体积和核浆比等均随剂量增加而加大，说明５－Ｆｕ可使细胞及细胞核明显增大；其中细胞及细胞核等效体积随剂量增加而增大幅度最大，细胞及细胞核面积随剂量增加而增大幅度其次。各参数与药物剂量之间有较好的依赖关系，呈正相关。各参数与药后时间亦有明确的依赖关系     

化学物致畸作用阈值判断──兼讨论烯效唑的致畸测试结果与ADI的制订

化学物致畸作用阈值判断──兼讨论烯效唑的致畸测试结果与ＡＤＩ的制订李颖，薛寿征（上海医科大学劳动卫生学教研组上海２０００３２）１、基线剂量值（ＢＭＤ）简介发育毒理学最近推出基线剂量（ＢＭＤ）作关键指标，它是增加５％效应剂量的９５％可信限下限值。ＢＭＤ...     

抗人肺癌单抗LC—1对荷人肺腺癌裸鼠的放射免疫定位

我们以荷人肺腺癌（ＬＡＸ－８３）裸鼠为动物模型，注入１３１Ｉ－ＬＣ－１，结果显示：注入１３１Ｉ－ＬＣ－Ｉ９６小时后，除脾、肾外，其余组织每克所含ｃｐｍ值均小于相同重量的肺癌组织；注入１３１Ｉ－ＬＣ－Ｉ１２０小时后，除血液外，其余各组织每克所含ｃｐｍ值均小于肺癌组织；肺腺癌细胞上１３１Ｌ－ＬＣ－１能被部分洗脱，但还保持一定含量。     

Stability and pharmacokinetics of m-[131I]iodobenzylguanidine in patients

A pharmacokinetic study was done to elucidate the body distribution, elimination, and metabolism of m-[131I]iodobenzylguanidine (m-[131I]IBG). For this purpose, an analytical method using solid phase extraction columns was developed. m-[131I]IBG was administered as an i.v. infusion according to different schedules with doses of 7,055 to 13,580 MBq/m2. At the start of the infusion m-[131I]IBG accounted for 93.0 +/- 2.3% (SD; n = 10) of the total radioactivity. At the end of the infusion m-[131I]IBG accounted for 88.0 +/- 7.4%. The non-m-IBG-bound radioactivity was predominantly 131I. The pharmacokinetic parameters (n = 7) are adequately described by a three compartment model. The parameters for m-[131I]IBG were determined with a mean terminal half-life of 37.0 h, a volume of distribution of 307 liters/m2, and an area under the curve value of 1091 kBq x h/ml. The total body clearance was 189 ml/min/m2. The values for 131I showed a terminal half-life of 71.6 h, a volume of distribution of 190 liters/m2, and an area under the curve value of 1537 kBq x h/ml. The total body clearance was 70 ml/min/m2. The selectivity of the m-[131I]IBG treatment might be improved by a reduction of 131I in the infusion fluid and further investigations are warranted.     

Microsatellite instability in primary and metastatic colorectal cancers

Microsatellite instability characterizes a sub-set of sporadic colorectal cancers (CRCs) as well as CRCs from patients with hereditary non-polyposis colorectal cancer (HNPCC). In order to clarify when the cells acquire a replication-error phenotype (RER) during colorectal-tumor progression, we examined the incidence of RER in 80 primary tumors and 36 liver metastases at 8 microsatellite loci; I mono-, 5 di-, I tetra- and I penta-nucleotide. RER were detected in 20.1% (17/80) of primary tumors, including 5 tumors showing RER at 2 or more loci (RER2), while the incidence of RER in liver metastases (22.2%, 8/36) was almost the same as that in primary tumors, and there was only one RER2 case in metastases. There were 3 cases in which both primary tumors and liver metastases had the same type of RER at the same locus, and there were 2 cases that showed RER in primary tumors but not in liver metastases. In contrast, there was no case in which RER was detected in a metastasis but not in the corresponding primary tumor. The RER phenotype did not show correlation with any clinicopatho-logical parameters of cancer-cell aggressiveness, such as clinical staging, histological grade and survival. These results indicate that a sub-set of CRCs acquire the RER phenotype in the relatively early stages of colorectal carcinogenesis, and that the RER phenotype is not associated with aggressiveness of CRCs. © 1995 Wiley-Liss, Inc.     

Targeting of meta-iodobenzylguanidine to SK-N-SH human neuroblastoma xenografts: tissue distribution, metabolism and therapeutic efficacy

The clinical results of [(131)I]meta-iodobenzylguanidine (MIBG)-targeted radiotherapy in neuroblastoma patients is highly variable. To assess the therapeutic potential of [(131)I]MIBG, we used the SK-N-SH human neuroblastoma, xenografted in nude mice. The model was first characterized for basic parameters of MIBG handling in the host species. This demonstrated the presence of both strain- and nu/nu mutation-related differences in [(131)I]MIBG biodistribution. Fecal and urinary clearance rates of [(131)I]MIBG in mice roughly resemble those in humans, but mice metabolize MIBG more extensively. In both species, enzymatic deiodination in vivo was not an important metabolic route. Therapy with increasing [(131)I]MIBG doses (25-92 MBq) given as single i.v. injections resulted in proportionally increasing specific growth delay values (tumor regrowth delay/doubling time) of 1 to 5. Using gamma-camera scintigraphy for non-invasive dosimetry, the corresponding calculated absorbed tumor radiation doses ranged from 2 to 11 Gy. We also compared the therapeutic effects of a single [(131)I]MIBG administration with those resulting from a more protracted exposure by fractionating the dose in 2 to 6 injections or with high dose rate external-beam irradiation. No therapeutic advantage of a fractionated schedule was observed, and 5.5 Gy delivered by low dose-rate [(131)I]MIBG endo-irradiation was equi-effective with 5.0 Gy X-rays. The SK-N-SH neuroblastoma xenograft model thus appears suitable to evaluate possible treatment improvements to reach full potential of MIBG radiotherapy.     

Radiation doses to the cell nucleus in single cells and cells in micrometastases in targeted therapy with (131)I labeled ligands or antibodies

PURPOSE: The aim of this study was to theoretically investigate how the radiation dose to cell nuclei depends on the subcellular position of (131)I. The influence of the size of the cells and crossfire irradiation in clusters of cells was also studied. METHODS AND MATERIAL: Using data describing the dose rate around a point source of (131)I, we calculated the dose distributions inside and around cell models of different sizes. The assumed positions of (131)I were on the cellular or nuclear membrane, in the cytoplasm, in the nucleus, or spread in the whole cell. The mean doses to the nucleus of the targeted cell and to the nuclei of its neighbors were calculated using the dose distributions. RESULTS: The dose distributions inside a single targeted cell showed very different distribution profiles depending on the subcellular position of the (131)I. Targeting the nucleus instead of the cellular membrane could increase the dose to the nucleus 10-fold. Crossfire irradiation can be the major contributor to the nuclear dose in clusters of more than six cells. CONCLUSIONS: Dosimetry without microscopic considerations is inadequate for targeted radionuclide therapy of disseminated or clustering tumor cells exposed to (131)I. Therapeutic doses could be achieved, even in single cells, when (131)I was positioned near, or inside the cell nucleus, or when the clusters were large enough.     

Biodistribution and dosimetry following infusion of antibodies labeled with large amounts of 131I.

Dosimetry and treatment planning for therapeutic infusions of radiolabeled antibodies are usually performed by extrapolation from the biodistribution of trace-labeled antibody. This extrapolation assumes that the biodistribution of high specific activity antibody will be similar to that seen with trace-labeled antibody. However, high doses of radiation result in rapid depletion of lymphoid and hematopoietic cells in lymph nodes, spleen, and marrow with replacement by blood and plasma. If radiolabeled antibody is cleared slowly from blood, this replacement may result in increased radionuclide concentrations in these tissues following infusions of antibody labeled with large amounts of radionuclide. To examine the influence of deposited radiation on the biodistribution of radiolabeled antibody, we treated mice with a constant amount of antibody that was labeled with varying amounts of 131I. Survival was determined in normal specific pathogen-free AKR/Cum mice (Thy1.2+) after infusion of anti-Thy1.1 antibody labeled with 10 to 6500 muCi of 131I, to determine an appropriate range of 131I doses for further study. The dose producing 50% lethality within 30 days following infusion of 131I-labeled antibody was 530 muCi 131I. Biodistribution, bone marrow histology, and dosimetry were subsequently determined after infusion of 500 micrograms of antibody labeled with 10, 250, 500, or 3500 muCi 131I. The amount of 131I did not influence uptake or retention of antibody in blood, liver, lung, or kidney. In contrast, infusion of antibody labeled with 250 to 3500 muCi of 131I led to a dose-related increase in the concentration of 131I in marrow, spleen, lymph node, and thymus. For example, at 96 h after infusion of antibody labeled with 500 or 3500 muCi 131I, concentrations in marrow were 3- to 4-fold higher than after infusion of trace-labeled antibody. The increase in marrow 131I concentrations was associated with depletion of cells and hemorrhage within the marrow space. As a result, estimated mean absorbed doses to marrow, lymph node, spleen, and thymus were 1.2 to 3.1 times higher than would have been predicted from the biodistribution of trace-labeled antibody. These results suggest that the biodistribution of trace-labeled antibody should be an accurate predictor of the behavior of high specific activity antibody in blood and solid organs such as liver and kidney. In contrast, radiation from antibody labeled with large amounts of radionuclide can result in an alteration of the concentration of radiolabeled antibody in rapidly responding tissues such as marrow.(ABSTRACT TRUNCATED AT 400 WORDS)     

Single-cell dosimetry for radioimmunotherapy of B-cell lymphoma patients with special reference to leukemic spread

AIMS: Many lymphoma patients have both macroscopic tumors and single-cell manifestations of their disease. Treatment efficacy could, therefore, depend on the radionuclide used. The aim of this study was to investigate dosimetry at a cellular level for three isotopes of radioiodine. METHODS: Cells were assumed to be spherical with radii of 6.35, 7.7, and 9.05 microm corresponding to the dimensions of the Raji cells. The radius of the nucleus was assumed to be 75% of the cellular radius. The electron energies were 18, 28, and 190 keV, corresponding to the mean electron energy per decay for (125)I, (123)I, and (131)I, respectively. S-values for different activity distributions were simulated using Monte Carlo and dose-volume histograms as well as absorbed doses, and absorbed dose rates were calculated. RESULTS: (125)I gives the highest absorbed dose (approximately 4-40 times that of (131)I), whereas (123)I will give the highest absorbed dose rate (approximately 100 times that of (131)I). Under the given assumptions, the absorbed dose at this level is more dependent on the size of the cells than on whether the radioimmunoconjugate is internalized. CONCLUSIONS: This enquiry showed that both (123)I and (125)I have greater potential than (131)I for the treatment of leukemic spread in patients with lymphoma.     

Radiological Impact of Atmospheric Nuclear Weapons Tests at Mururoa and Fangataufa Atolls to Populations in Oceania,South America and Africa: Comparison with French Polynesia

Objective: To evaluate the potential radiological impact of atmospheric nuclear weapons tests conducted in 1966-1974 at Mururoa and Fangataufa atolls on populations in Oceania, South America and Africa. Methods: Results of measurements of total beta(β)-concentrations in filtered air and 131I activity concentrations in locally produced cow’s milk in Oceania, South America and Africa after the tests were compared with those in French Polynesia. Radiation doses due to external irradiation and thyroid doses due to 131I intake with milk by local populations were also compared. Results: Higher total β-concentrations in filtered air, 131I activity concentrations in locally produced milk and radiation doses to local population were, in general, observed in French Polynesia than in other countries in the southern hemisphere. However, for specific years during the testing period, the radiological impact to South America was found to be similar or slightly higher than that to Tahiti. The resulting thyroid doses in the considered countries were lower than those in French Polynesia with two exceptions: thyroid doses due to 131I intake with cow’s milk for 1-y old child in 1968 were higher in Peru (0.35 mGy) and in Madagascar (0.30 mGy) than in Tahiti (0.25 mGy). However, the populations outside French Polynesia received doses lower than those from the natural sources of radiation. Conclusion: According to the current knowledge in radiation epidemiology, it is very unlikely that nuclear fallout due to French nuclear tests had a measurable radiological and health impact outside French Polynesia.     

High-dose radioiodine treatment for differentiated thyroid carcinoma is not associated with change in female fertility or any genetic risk to the offspring

BACKGROUND: We tried to evaluate the female fertility and genetic risk to the offspring from the exposure to high-dose (131)I by assessing the pregnancy outcomes and health status of the children of female patients with differentiated thyroid cancer who had received therapeutic doses of (131)I. MATERIALS AND METHODS: From 1967 to 2002, a total of 1,282 women had been treated with (131)I. Of these patients, 692 (54%) were in the reproductive age group (18-45 years). Forty women had a total of 50 pregnancies after high-dose (131)I. Age at presentation ranged from 16 to 36 years (mean, 23 +/- 4 years). Histopathology was papillary thyroid cancer in 32 cases and follicular thyroid cancer in 8 cases. RESULTS: Single high-dose therapy was given in 30 cases, 2 doses were given in 7 cases, 3 doses were given in 2 cases, and four doses were given in 1 case in which lung metastases had occurred. In 37 patients (92%), disease was successfully ablated before pregnancy. Ovarian absorbed-radiation dose calculated by the MIRD method ranged from 3.5 to 60 cGy (mean, 12 +/- 11 cGy). The interval between (131)I therapy and pregnancy varied from 7 to 120 months (37.4 +/- 28.2 months). Three spontaneous abortions occurred in 2 women. Forty-seven babies (20 females and 27 males) were born. Forty-four babies were healthy with normal birth weight and normal developmental milestones. Twenty women delivered their first baby after (131)I therapy. The youngest child in our series is 11 months of age, and the oldest is 8.5 years of age. CONCLUSIONS: Female fertility is not affected by high-dose radioiodine treatment, and the therapy does not appear to be associated with any genetic risks to the offspring.     

Tumors after radiotherapy for thyroid cancer. A case-control study within a cohort of thyroid cancer patients.

A case-control study of Swedish thyroid cancer patients was conducted to evaluate the possible influence of 131I treatment and external radiotherapy on the risk of developing a subsequent cancer. Both cases and controls derived from a cohort of Swedish thyroid cancer patients treated with 131I (n = 834) or by other means (n = 1,121). Thirty-six breast, 13 stomach, 12 kidney, and 5 bladder cancers were found more than 2 years after 131I treatment/thyroid cancer diagnosis. Individual, absorbed dose in the organs was calculated by using ICRP tables, administered activity of 131I, and 24-h 131I uptake. In studying the effect of 131I and external radiotherapy no statistically significant dose-response relationships were found for cancers of the breast, stomach, bladder or kidney. When the absorbed dose from 131I was analyzed separately the risks remained essentially the same. The present follow-up time and the relatively low absorbed dose that the patients received from 131I and external radiotherapy necessitate studies with a longer follow-up time or a larger patient material before more firm conclusions can be made.     

The significance of I-131 treatment of metastatic thyroid-carcinoma

The benefit of I-131 therapy of metastatic differentiated thyroid carcinoma is controversial. To evaluate usefulness of I-131 therapy for metastatic differentiated carcinoma, 83 patients were chosen from 276 patients with differentiated thyroid carcinoma who were operated at Nagasaki University Hospital since 1960 according to the following criteria; (i) thyroids totally removed, (ii) existence of metastases at total thyroidectomy, (iii) the cause of death related to thyroid carcinoma if the patient died. The usefulness of I-131 therapy was evaluated by analysis of survival during 10 years following total thyroidectomy. In patients without remote metastases, the survivors and nonsurvivors were 37 and 2 in those without I-131 therapy (Group I), and 11 and 1 in those with I-131 therapy (Group II), respectively. There was no significant difference between the two groups. In patients with remote metastases, the survivors and non survivors were 9 and 1 in I-131 treated patients who had I-131 accumulation in the metastases with tracer doses (Group III-1), 1 and 11 in I-131 treated patients without I-131 accumulation in metastases with tracer doses (Group III-2), and 4 and 6 in non I-131 treated patients whose metastases were not examined for I-131 accumulation (Group IV), respectively. The prognosis was best in Group III-1 and followed by Group IV and Group III-2 in this order in patients with remote metastases. There was no significant difference in age and sex among the groups and in pathological findings of carcinoma. These results suggest that I-131 therapy may be useful for patients with remote metastases which accumulate I-131 with tracer doses but not for those patients who do not accumulate I-131 and that I-131 accumulation in metastases with tracer doses may be of prognostic significance.