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。     

共面模板辅助CT引导下125I粒子植入治疗脊柱转移瘤疗效分析

目的 探讨共面模板（co-planar template, CPT）辅助CT下植入¹²⁵I放射性粒子近距离治疗脊柱转移瘤质量控制与近期疗效。方法 12例原发肿瘤经病理学明确诊断,影像学改变符合脊柱转移瘤特征,患者共有16个病灶。处方剂量（prescribed dose, PD）80 Gy,粒子活度（1.48×10⁷~2.59×10⁷）Bq（0.4~0.7 mCi）,CPT辅助CT引导下将植入针按术前计划穿刺并种植放射性¹²⁵I粒子。术后即刻扫描观察粒子分布情况,剂量评估。随访复查CT判定瘤体直径变化,进行疗效评估。随访时间为3~29个月。同时给予疼痛分级,评判疼痛改善情况。结果 16个病灶全部穿刺成功植入粒子。植入后剂量验证显示肿瘤靶区接受的平均照射剂量（209.21±37.16）Gy,D₉₀为（115.29±7.87）Gy,D₁₀₀为（76.59±5.53）Gy,V₉₀为（99.30±0.51）%,V₁₀₀为（98.06±1.15）%,适形指数（CI）0.981±0.012,靶区外体积指数（EI）0.012±0.007。脊髓接受的平均照射剂量为（30.47±4.83）Gy。靶区和脊髓接受的平均照射剂量与术前计划比较,差异无统计学意义（P>0.05）。术后3个月病灶完全缓解（CR）18.8%（3/16）, 部分缓解（PR）62.5%（10/16）,疾病进展（PD）6.25%（1/16）,疾病稳定 （SD）6.25%（1/16）,有效率（CR+PR）81.3%;疼痛完全缓解3例,部分缓解7例,轻度缓解2例;生存期11~39个月,中位生存期24个月。所有患者脊髓无放射性损伤发生。结论 应用CPT辅助CT引导可以按照术前计划控制粒子植入的位置和放射剂量,达到治疗肿瘤、并发症少、患者可耐受的目的。     

3D打印共面模板辅助CT引导125Ⅰ粒子植入治疗非小细胞肺癌的剂量学研究

目的 探讨3D打印共面模板（3D-print coplanar template,3D-PCT）辅助CT引导 ¹²⁵Ⅰ粒子植入治疗非小细胞肺癌（NSCLC）的安全、有效及对剂量学的可控性。方法 选取2014年5月到2016年11月符合 ¹²⁵Ⅰ粒子植入适应证的NSCLC患者20例,其中3D-PCT辅助CT引导 ¹²⁵Ⅰ粒子植入治疗的患者10例（3D组）,CT引导徒手穿刺 ¹²⁵Ⅰ粒子植入治疗的患者10例（徒手组）,术前2 d内行CT定位扫描,得出医学数字成像和通信（digital imaging and communications in medicine,DICOM）数据,输入治疗计划系统（brachytherapy treatment planning system,BTPS）,行术前预计划。术后即刻行胸部CT扫描,术后质量验证。对比两组术前、术后剂量学参数,包括90%和100%的靶区体积所占的剂量D₉₀和D₁₀₀、100%和150%的处方剂量所占的靶区体积百分比V₁₀₀和V₁₅₀、适形指数（CI）、靶区外体积指数（EI）、均匀性指数（HI）。结果 3D组术前与术后剂量学参数V₁₅₀差异有统计学意义（t=-2.916,P< 0.05）,其他剂量学参数差异无统计学意义（P> 0.05）。徒手组术前与术后剂量学参数,包括粒子数、V₁₀₀、EI、HI差异有统计学意义（t=-2.516、2.492、4.725、7.258,P< 0.05）,其他剂量学参数差异无统计学意义（P> 0.05）。3D组术后剂量学参数和徒手组术后剂量学参数行单样本t检验,其中V₁₀₀、CI、EI、HI、剂量误差率差异有统计学意义（t=2.598、2.278、4.637、4.616、-4.785,P< 0.05）,两组术后V₁₅₀差异无统计学意义（P> 0.05）。结论 3D-PCT辅助CT引导¹²⁵Ⅰ近距离放射性粒子植入治疗NSCLC安全可行,剂量学可控,且在粒子空间分布方面较徒手穿刺具有一定优势。     

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。     

125I粒子联合化疗治疗局限期小细胞肺癌预后及影响因素分析

目的 评估CT引导下¹²⁵I放射性粒子植入联合全身化疗治疗局限期小细胞肺癌（limited-stage small cell lung cancer LS-SCLC）的临床疗效及影响预后因素。方法 2008年6月至2012年6月在天津医科大学第二医院接受¹²⁵I粒子植入联合全身化疗治疗的LS-SCLC患者128例。采用χ²检验对患者近期疗效影响因素进行分析。采用Kaplan-Meier法计算生存率,Log-rank进行单因素分析,采用Cox比例风险模型进行多因素分析。结果 全组128例患者治疗后,6个月总有效率86.7%（111/128）。1、2、3年生存率分别为77.9%、39.8%、28.0%;中位生存期21.0个月。单因素分析结果显示,年龄、一般状态（performance status,PS）、术前血红蛋白、吸烟指数、肿瘤直径、术前神经元特异性烯醇化酶（neuron-specific enolase,NSE）、是否接受预防性全脑照射（prophylactic cranial irradiation,PCI）、化疗周期数、化疗疗效、处方剂量、术后D₁₀₀、治疗模式均可影响LS-SCLC患者的生存。多因素分析结果显示,年龄、PS评分、术前血红蛋白、肿瘤直径、处理方剂量、化疗周期数、化疗疗效及治疗模式是LS-SCLC的独立预后因素。全组术中气胸29例占22.7%,咯血16例,占12.5%。结论 ¹²⁵I放射性粒子植入治疗LS-SCLC显示了较好的疗效,年龄、PS评分、术前血红蛋白、肿瘤直径、PD、化疗周期数、化疗疗效及治疗模式为LS-SCLC患者预后的主要影响因素。     

3D打印模板辅助CT引导放射性125I粒子植入治疗软组织肉瘤的剂量学研究

目的 通过对3D打印模板（共面和非共面）辅助治疗软组织肉瘤术前、术后的剂量学比较,探讨其应用的精确性。方法 2015年12月—2017年7月于北京大学第三医院接受3D打印模板辅助CT引导放射性¹²⁵I粒子植入的软组织肉瘤患者19例,共25处病灶。所有患者行术前病情评估、CT模拟定位、术前计划设计、3D模板打印、3D模板复位、插植粒子针和粒子植入、术后剂量学评估、术后护理及定期随访。对比术前、术后剂量学参数。筛选位于躯干及四肢浅部的软组织肉瘤10例,分别设计共面模板和非共面模板引导的术前计划,对比两种模板引导下术前计划的剂量学参数。结果 设计制作3D打印模板25块,共25处病灶,术前、术后剂量学参数差异无统计学意义（P>0.05）。位于躯干及四肢浅表并使用3D打印共面模板与非共面模板引导的术前计划各剂量学参数差异无统计学意义（P>0.05）。结论 应用3D打印模板辅助¹²⁵I粒子植入治疗软组织肉瘤具有较好的定位精确性。对位于躯干及四肢浅部的软组织肉瘤,建议优先选择3D打印共面模板。     

老年头颈癌患者125I粒子植入治疗后的生存质量研究

目的 评价老年头颈癌患者碘-125(¹²⁵I)粒子植入治疗后生存质量状况。方法 选择2005年至2011年就诊于本院因头颈癌行¹²⁵I粒子植入治疗的老年患者40例,采用QOL-RTI问卷对生存质量进行调查。评价其生存质量情况,并分析治疗后影响生存质量的因素。结果 40例入选患者,治疗后维持了良好的生存质量。老年舌根癌患者粒子植入后生存质量低于其他部位癌患者;老年患者功能状况和整体生存质量随年龄增加而降低;术后辅助¹²⁵I粒子植入治疗患者生存质量(QOL)高于未能完全切除或难以手术的患者;病理类型、粒子植入数量以及治疗后时长对患者生存质量无明显影响。结论 老年头颈癌患者行¹²⁵I粒子植入术后,维持有良好的生存质量。肿瘤靶区和临床分期是影响患者生存质量的重要因素。     

图像引导放射性125I粒子植入治疗复发性软组织肉瘤疗效以及临床预后因素分析

目的 观察图像引导下放射性¹²⁵I粒子植入治疗复发性软组织肉瘤的疗效和不良反应,分析临床因素与预后之间关系。方法 回顾分析2002年9月—2015年12月北京大学第三医院图像引导下采用放射性¹²⁵I粒子植入治疗的60例局部复发软组织肉瘤资料。入组患者KPS≥60分、拒绝或不能耐受再次手术、拒绝或不能耐受放疗、预计总生存时间>3个月的软组织肉瘤多重治疗后复发,行CT或超声引导性放射性¹²⁵I粒子植入治疗。本组患者中位粒子活度为25.9×10⁶ Bq（11.1×10⁶~29.6×10⁶ Bq）,植入粒子中位数为58颗（3~133）,中位D₉₀为120 Gy（36.50~460.97 Gy）。评价患者总生存（OS）时间和局部无进展生存（LPFS）时间及其与临床因素的关系。Kaplan-Meier计算OS率和LPFS率。Log-rank检验和Cox回归进行单因素和多因素分析。结果 中位随访时间18.75个月（1~146个月）。中位OS时间18.5个月（95%CI 13.1~23.9）,1、3、5年OS率分别为63.3%、33.0%、29.5%。1、3、5年LPFS率分别为72.5%、63.7%、59.7%。疼痛缓解率为100%（6/6）。8.3%（5/60）患者出现4级皮肤反应,无致死性并发症发生。单因素分析显示,肿瘤最大径 < 7 cm、既往应用化疗、KPS评分、是否伴有全身转移、肿瘤体积 < 45 cm³、D₉₀ > 110 Gy是影响OS的预后因素;肿瘤最大径 < 5 cm、KPS评分、体积 < 40 cm³、D₉₀ > 95 Gy是影响LPFS的预后因素。多因素分析显示既往化疗和伴有全身多发转移是影响总生存的预后因素。结论 图像引导下¹²⁵I粒子植入治疗复发性软组织肉瘤,局部控制好,是一种安全、有效的挽救治疗手段。肿瘤大小、D₉₀是影响OS和LPFS的主要因素。     

携带125I粒子导管和徒手粒子植入模拟病灶后粒子纵向间距准确性的对比研究

目的 对比携带¹²⁵I粒子的可降解导管植入和徒手粒子植入后粒子纵向间距的准确性。方法 本研究用薯蓣制成24个模拟病灶,分为徒手组和粒子导管组,每组12个模拟病灶,由3位医师完成粒子和粒子针插植,每位医师每组插植4个病灶,每组共插植60针道,并按设定粒子间距（0.5和1.0 cm）分别在两组模拟病灶内行粒子植入。术后CT复查,并测量粒子纵向间距。配对t检验分析徒手组和导管组与设定间距偏离的差异。结果 徒手组与设定间距的偏离程度分别为（0.184±0.047）和（0.127±0.051）cm,导管组与设定间距的偏离程度分别为（0.007±0.006）和（-0.003±0.006）cm,导管组粒子的偏离程度明显小于徒手组（t=3.804、2.499,P<0.05）。结论 携带¹²⁵I粒子导管的应用,使粒子纵向间距的准确性优于徒手组,受术者的影响较小。     

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。     

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.}     

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.     

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 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.     

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。     

Scintigraphic findings of MALT lymphoma of the thyroid

Mucosa-associated lymphoid tissue (MALT) lymphoma has been established as a distinct entity among non-Hodgkin's lymphomas, and the most common primary site is the stomach. We describe scintigraphic findings in a patient with MALT lymphoma of the thyroid. A 71-year-old woman with Hashimoto's thyroiditis suffered from rapid cervical swelling, and ultrasonography and CT revealed a thyroid nodule. The nodule showed accumulation of 99mTc pertechnetate comparable to the surrounding thyroid tissue, mimicking a benign nodule. Both 67Ga and 201Tl imaging visualized the lesion as an increased uptake area. After radiotherapy, abnormally increased uptake disappeared on 67Ga images, which predicted a favorable outcome. MALT lymphoma of the thyroid may be visualized as a warm nodule on 99mTc pertechnetate scintigraphy.     

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.     

The role of I-131-MIBG in the diagnosis and therapy of carcinoids

The successful use of ¹³¹I-MIBG for the diagnosis and treatment of pheochromocytoma and neuroblastoma has led to its application in patients with carcinoid, another neural crest tumor. The present report describes the scintigraphic findings, in correlation with clinical and biochemical parameters, in 20 patients with histologically proven carcinoids. ¹³¹I-MIBG total body scintigraphy was positive in 12 and equivocal in 1 of 19 patients with metastases. The necessity of delayed imaging and the possible advantage of single photon emission tomography for the detection of this tumor are emphasized. The results of ¹³¹I-MIBG treatment in five patients with progressive carcinoid metastases are discussed. It is concluded that ¹³¹I-MIBG has a role in the work up of patients with proven carcinoid and can be used for palliative treatment of this tumor.     

Development of a modular system for the synthesis of PET [C]labelled radiopharmaceuticals

[¹¹C]labelled radiopharmaceuticals as N-[¹¹C]methyl-choline ([¹¹C]choline), l-(S-methyl-[¹¹C])methionine ([¹¹C]methionine) and [¹¹C]acetate have gained increasing importance in clinical PET and for the routine production of these radiopharmaceuticals, simple and reliable modules are needed to produce clinically relevant radioactivity. On the other hand, flexible devices are needed not only for the routine synthesis but also for more complex applications as the development of new tracers. The aim of this work was the adaptation of an Eckert Ziegler modular system for easy routine synthesis of [¹¹C]choline, [¹¹C]methionine and [¹¹C]acetate using components that account for straightforward scaling up and upgrades.