125I放射性粒子组织间植入治疗腮腺癌专家共识(2023年版)

¹²⁵I放射性粒子组织间植入治疗是腮腺癌主要治疗方法之一,具有局部剂量高和周围组织损伤小的特点。放射性粒子治疗效果与剂量、精度密切相关。然而,¹²⁵I放射性粒子在腮腺癌中的应用尚无明确规范,各治疗中心对于放射性粒子治疗的标准不尽相同。为进一步规范腮腺癌近距离放射治疗流程,经国内多位专家反复讨论后达成一致意见,制定本共识。本共识对¹²⁵I放射性粒子组织间植入治疗腮腺癌的适应证与禁忌证、治疗参数、操作流程、技术规范、放射防护、不良反应、随访等给出了规范化建议,可供临床实践参考。     

美国退伍军人医院前列腺癌粒子植入医疗不良事件介绍

放射性粒子植入作为早期前列腺癌的标准治疗手段,在美国已广泛开展。美国近距离治疗协会及美国医学物理学家协会有明确的指南来加以规范,但是仍有部分医院不能按照指南要求植入粒子,导致部分患者出现严重并发症。本文调研了美国放射性粒子植入相关医疗事件,对美国2002年以来发生的粒子植入医疗事件进行了梳理,分析其发生的原因,提出相应的解决方案,为我国粒子植入从业人员提供参考,以防类似事件发生,保障粒子植入术的健康发展。     

2016年外照射个人剂量监测能力考核检测报告书写存在问题的分析

放射性粒子植入作为早期前列腺癌的标准治疗手段,在美国已广泛开展。美国近距离治疗协会及美国医学物理学家协会有明确的指南来加以规范,但是仍有部分医院不能按照指南要求植入粒子,导致部分患者出现严重并发症。本文调研了对美国放射性粒子植入相关医疗事件,对美国2002年以来发生的粒子植入医疗事件进行了梳理,分析其发生的原因,提出相应的解决方案,以便我国粒子植入从业人员参考,以防类似事件发生,保障粒子植入术的健康发展。     

放射性粒子植入计划系统剂量计算准确性验证

放射性粒子永久性植入作为一种近距离放疗技术,是早期前列腺癌根治性治疗手段之一,在我国也广泛应用于其他肿瘤的治疗.剂量分布是影响粒子植入疗效最直接、最重要的因素.粒子植入计划系统越来越多地应用于粒子植入的术前、术中计划和术后剂量验证.目前,放射性粒子植入计划系统剂量计算准确性验证方面尚少见报道.本研究验证Prowess Brachytherpay 3.1计划系统125Ⅰ粒子永久性植入剂量计算的准确性,并说明其剂量计算方法和实施细节,以确保其能够用于临床.     

放射性125Ⅰ粒子组织间植入治疗盆腔恶性肿瘤的研究进展

放射性 ¹²⁵Ⅰ粒子组织间植入具有低剂量率、持续照射、可反复植入等特点,目前常应用于宫颈癌的治疗,也适用于卵巢癌、结直肠癌、膀胱癌等盆腔恶性肿瘤。与外放疗相比,¹²⁵Ⅰ粒子近距离治疗可提高肿瘤靶区剂量,有效控制局部肿瘤,同时保护周围正常组织,减少并发症。现从 ¹²⁵Ⅰ粒子组织间植入治疗盆腔恶性肿瘤的特性、作用机理、并发症以及临床应用的最新进展进行综述,同时介绍3D打印模板在粒子植入中的应用,为临床广泛推广提供一定的参考。     

3D打印技术在精准粒子植入治疗中的应用

近距离治疗是肿瘤重要的手段之一,具有局部剂量高和周围正常组织损伤小的优势。 近距离治疗包括高剂量率和低剂量率两种,其中低剂量率近距离治疗是直接将放射性核素植入到肿瘤体内对肿瘤细胞进行杀伤,亦称放射性粒子组织间永久植入治疗,简称粒子植入,在早期前列腺癌治疗中取得与手术和外照射同样的疗效。3D打印技术是通过影像学图像将信息传输到计算机计划系统,以数字化设计文件为基础,通过计算机设计针道、定义处方剂量,之后3D打印机打印出个体化引导模板,引导粒子针插植和粒子植入,经头颈部、胸、腹部和盆腔初步验证,治疗精度大大提高,粒子植入治疗成为可计划、可优化和可评估的标准技术手段,开启放射性粒子组织间植入治疗全新时代。     

125I放射性粒子治疗腮腺复发性腺样囊性癌的靶区设计及剂量学分析

目的 分析¹²⁵I放射性粒子单纯植入治疗腮腺区复发性腺样囊性癌的靶区设计方法及剂量学参数。方法 回顾性分析2005年1月至2019年10月北京大学口腔医院收治的行单纯¹²⁵I放射性粒子近距离植入治疗的25例复发性腮腺腺样囊性癌患者的靶区设计及剂量学参数。术前结合腺样囊性癌病理学特点对不同复发部位设计靶区范围,处方剂量为100~120 Gy,术后验证靶区范围与剂量学参数。随访统计局部控制情况及放疗相关不良反应。结果 25例患者复发部位分别为腮腺浅叶区10例,腮腺深叶区7例,颅底区及乳突颌后区复发各4例。中位植入粒子数量为59颗,粒子活度18.5~25.9 MBq,植入后验证所有患者均实现植入前靶区设计范围,D₉₀、V₁₀₀、V₁₅₀等剂量学参数与植入前相近,差异无统计学意义（P>0.05）。3年、5年局部控制率分别为81.5%和61.5%,不同部位的局部控制率差异无统计学意义（P>0.05）。结论 单纯应用¹²⁵I放射性粒子植入治疗腮腺区复发性腺样囊性癌,通过结合病理学特点及复发部位优化靶区设计,合理准确应用达到剂量学参数,可获得较好的局部控制。     

125I粒子治疗儿少期头颈部交界瘤的靶区与剂量设计

目的总结并评价儿少期头颈部交界性肿瘤125I放射性粒子植入方案的靶区与剂量设计。方法选择2010年1月至2018年12月间于北京大学口腔医院就诊经单纯125I放射性粒子组织间植入近距离治疗或联合手术治疗的儿少期交界性肿瘤患者11例, 以大体肿瘤靶区外扩0.5～1.0 cm为计划靶区, 处方剂量80～120 Gy, 活度为18.5 MBq, 全麻下按治疗计划将125I放射性粒子植入靶区。术后进行随访, 记录疗效及不良反应。评析粒子植入前、后剂量学参数以及局部控制率、客观缓解率和不良反应发生率。结果 11例儿少期患者粒子植入前、后剂量学参数差异无统计学意义(P>0.05)。随访33～131个月, 中位时间48个月。局部控制率100%, 完全缓解率71.4%, 客观缓解率100%, 急性不良反应率81.8%。结论 125I放射性粒子植入治疗儿少期头颈部交界瘤, 在合理的靶区及剂量设计下, 可获得满意的临床疗效且不良反应较低, 是一种可行的治疗手段。     

125I放射性粒子治疗复发性腮腺癌24例临床分析

目的 探讨应用¹²⁵I放射性粒子组织间植入近距离放疗在腮腺区复发恶性肿瘤的临床应用及疗效。方法 回顾性分析2006年至2013年,就诊于北京大学口腔医院,经放射性¹²⁵I粒子组织间植入治疗的24例复发腮腺腺源性恶性肿瘤患者的临床资料,所有患者均为临床Ⅳ期。定期随访,观察并分析局部控制率,生存率及不良反应。结果 24例复发肿瘤患者,随访时间4至59个月。6例局部控制失败,10例患者死亡。患者1年、3年生存率分别为74.8%和39.3%,1年、3年无进展生存率分别为74.8%和31.5%,1年、3年局部控制率分别为82.0%和69.4%。无3级以上放射性损伤。结论 单纯放射性¹²⁵I粒子组织间植入治疗,对于无法手术切除的复发腮腺恶性肿瘤患者,为可选治疗方式,局部控制率较好。     

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。     

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。     

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.     

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.     

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 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.     

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.     

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.