肝胆肿瘤患者68Ga-FAPI-04 PET显像的内照射剂量及分布研究

目的 评估⁶⁸Ga-FAPI-04 PET/CT检查在肝胆肿瘤患者中的内照射剂量及生物分布。方法 本研究纳入因肝脏占位于北京协和医院接受PET/CT检查的6例患者,经静脉注射⁶⁸Ga-FAPI-04（170.57 ±14.43） MBq后分别于第3、10、15、20、30和60 min进行全身显像。观察显像剂的生物分布;手动勾画感兴趣区;所有靶器官的内照射剂量应用OLINDA/EXM软件计算。结果 ⁶⁸Ga-FAPI-04在肝脏内放射性本底消退较快,在肿瘤组织内放射性摄取较为稳定,病灶平均SUV_max在注射后20 min达到最大（13.87 ±2.55）;病灶平均靶本比逐渐升高,在注射后30 min达到最大（10.09 ±8.17）。1次⁶⁸Ga-FAPI-04 PET/CT扫描的全身有效剂量为（0.020 ±0.002） mSv/MBq,吸收剂量最高的器官是膀胱壁,为（0.146 ±0.035） mSv/MBq。结论 ⁶⁸Ga-FAPI-04与¹⁸F-FDG全身有效剂量相近;肿瘤摄取快速,肝脏背景低,且不受血糖水平影响,有望成为潜在的肝胆肿瘤PET/CT显像药物。     

分化型甲状腺癌患者口服131I后体内活度变化及剂量水平

目的 研究¹³¹I治疗分化型甲状腺癌（DTC）患者体内放射性活度及外部剂量水平的变化规律，分析二者之间的关系，并估算400 MBq患者剂量当量率的修正因子。方法 研究对象为43例甲状腺全切术后，首次行¹³¹I"清甲"治疗的DTC患者，服药量为1 850~3 700 MBq，平均服药量（2 405±777）MBq。分别于口服¹³¹I后2、6、20、22、24、27、30、44、46、48、54、68及72 h，测定患者的体内剩余放射性活度以及患者前部0.3、1及3 m处的剂量当量率。结果 患者服¹³¹I后的体内剩余放射性活度随时间变化函数为A=A₀（1.033 16e^{-0.062 4t}+0.017 17）。可估算出"清甲"治疗的DTC患者有效半减期为12.19 h，体内放射性活度降至400 MBq仅需26.4~38.9 h。患者服用¹³¹I后距其0.3、1及3 m的标准化剂量当量率随时间变化函数分别为：Ḣ_0.3=127.220 7e^{-0.054 8t}+3.765 71、Ḣ₁=30.225 8e^{-0.064 4t}+0.824 67、Ḣ₃=4.161 9e^{-0.061 5t}+0.167 97。患者服¹³¹I后体内剩余放射性活度与1 m处剂量当量率呈正相关（r=0.982，P<0.05），函数为Ḣ₁=0.025A+1.245。DTC患者体内剩余活度分别为1 000、700和400 MBq时，距患者1 m处对应的剂量当量率分为26.2、18.7和11.2 μSv/h。估算活度为400 MBq的患者0.3、1及3 m处剂量当量率的修正因子分别为0.25、0.49及0.70。结论 服用¹³¹I活度在3 700 MBq以下的DTC患者仅需住院2日便可达到出院标准。当DTC患者体内活度降至400 MBq时，其1 m处的剂量当量率远小于25 μSv/h。单纯利用点源公式估算患者周围剂量当量率会造成高估的情况，因此对于公式估算患者周围辐射水平时使用的修正因子还需进一步研究，使模型估算结果更贴合实际情况。     

放射性125I粒子植入对人肺腺癌裸鼠移植瘤微血管生成的影响

目的 探讨放射性¹²⁵I粒子植入对人肺腺癌裸鼠移植瘤微血管生成的影响及其作用机制。方法 制备人肺腺癌细胞A549裸鼠皮下移植瘤模型24只,采用随机数字表法分为4组,每组6只,0、22.2、29.6 MBq组和对照组。用18 G植入针在各组裸鼠瘤体内分别植入放射活度为0、22.2和29.6 MBq ¹²⁵I粒子,每个移植瘤内植入一枚,对照组不予处理。观察肿瘤生长情况,每4天测量肿瘤大小。30 d后处死裸鼠,绘制肿瘤生长曲线。瘤组织免疫组织化学S-P法检测微血管密度（microvascular density,MVD）,并分别用RT-PCR、Western blot法检测血管内皮生长因子（vascular endothelial growth factor,VEGF）和缺氧诱导因子-1α（hypoxia inducible factor-1α,HIF-1α）的mRNA及蛋白的表达。结果 粒子植入治疗后54 d,22.2、29.6 MBq组移植瘤体积明显小于对照组（q=14.117、17.075,P<0.05）,但0 MBq组与对照组、22.2与29.6 MBq组瘤体积差异均无统计学意义（P>0.05）。CD34阳性染色结果显示,22.2 MBq组的MVD为522±119,29.6 MBq组为491±121,明显低于对照组的922±260（q=4.826、5.197,P<0.05）,但0 MBq组与对照组、22.2 MBq组与29.6 MBq组差异均无统计学意义（P>0.05）。RT-PCR检测表明,22.2 MBq组的VEGF和HIF-1α mRNA相对表达量分别为0.279±0.0659和0.370±0.0857,29.6 MBq组为0.215±0.0620、0.278±0.0651,均低于对照组（q=18.881、17.211和15.376、14.733,P<0.05）,但0 MBq组与对照组、22.2 MBq组与29.6 MBq组之间差异均无统计学意义（P>0.05）。Western blot结果显示,22.2 MBq组与29.6 MBq组瘤组织VEGF和HIF-1α蛋白表达均明显减少,与对照组相比,差异有统计学意义（q=5.848、6.263和6.560、7.576,P<0.05）,但0 MBq组与对照组以及22.2 MBq组与29.6 MBq组差异均无统计学意义（P>0.05）。结论 放射性¹²⁵I粒子植入能有效抑制人肺腺癌裸鼠移植瘤微血管生成。     

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。     

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。     

核医学场所空气中131I浓度监测及工作人员内照射剂量评价探讨

目的 了解医疗机构¹³¹I治疗工作场所空气中¹³¹I核素的活度浓度水平,探讨通过空气采样方法估算工作人员内照射剂量的方法并分析其影响因素。方法 选取郑州市10家开展¹³¹I核素治疗的工作场所,采用空气采样方法采集¹³¹I治疗工作场所中放射性气溶胶,用高纯锗γ能谱仪进行γ放射性核素测定并推算工作场所空气中¹³¹I核素的活度浓度水平,根据测量结果和现场调查结果估算放射工作人员因¹³¹I核素吸入导致的内照射剂量。结果 19个分装间空气样品的¹³¹I活度浓度为0.087~570 Bq/m³,平均为（51.04±128.58）Bq/m³;11个病房空气样品的¹³¹I活度浓度为0.162~54.6 Bq/m³,平均为（7.97±15.89）Bq/m³。根据GBZ 129-2016《职业性内照射个人监测规范》推荐的典型工作时间估算,放射工作人员由于吸入¹³¹I核素导致的年待积有效剂量范围为2 μSv~10 mSv,平均为（0.61±1.80）mSv,年有效剂量均未超过国家标准所规定的剂量限值。结论 郑州市10家医疗机构核医学工作场所中¹³¹I核素活度浓度较高的样品多分布在甲状腺癌住院患者较多、核素操作量较大的三甲医院,由此导致的工作人员内照射剂量不容忽视。根据空气样品的测量结果估算内照射剂量带有很大不确定度,但空气采样方法可及时发现异常或事故情况下的放射性污染,为工作人员开展体外直接测量和内照射评价提供预警。     

CT头颈部检查所致婴幼儿眼晶状体吸收剂量估算方法的模体研究

目的 探讨CT不同扫描方案检查所致婴幼儿眼晶状体吸收剂量估算方法,并寻求快速估算眼晶状体吸收剂量的实用方法。方法 通过设置7种临床标准扫描方案,对1岁年龄组仿真模体进行扫描,利用布放在模体不同位置的热释光探测器（TLD）测量剂量,最后测量结果分别用组织因子转换和个人剂量当量转换两种方法来估算眼晶状体吸收剂量,同时将眼晶状体吸收剂量与CT剂量指数（CTDI）建立线性回归方程。结果 7种临床标准儿童扫描方案CT检查所致的婴幼儿眼晶状体吸收剂量分别为（9.96±0.69）mGy（头部轴向）、（7.01±0.42）mGy（头部螺旋）、（12.60±0.97）mGy（副鼻窦）、（12.97±0.42）mGy（内耳高分辨）、（0.63±0.03）mGy（颈部软组织）、（8.89±0.44）mGy（颈部颈椎）和（0.34±0.01）mGy（胸部常规）,不同组之间剂量差异有统计学意义（F=846.826,P<0.05）。不同扫描部位,CTDI值与眼晶状体吸收剂量之间均存在线性关系（r=0.986~0.999,P<0.05）。结论 采用儿童CT扫描条件,婴幼儿眼晶状体吸收剂量单次剂量范围一般不会超过阈剂量。另外,通过读取CTDI值,利用线性关系,可快速估算眼晶状体吸收剂量。     

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。     

化疗联合125I粒子治疗不能手术的肺上沟癌的疗效分析

目的 探讨应用放射治疗计划系统（TPS）在CT引导下经皮穿刺种植放射性¹²⁵I粒子近距离联合化疗治疗肺上沟癌的疗效分析。方法 回顾性分析2002年12月至2010年12月本院收治的影像及病理证实为肺上沟癌的患者36例,其中鳞癌26例,腺癌10例。粒子植入后1周行化疗,具体方案为第1、8天静脉给予1 000 mg/m²吉西他滨,第1天静脉给予顺铂75 mg/m²,连续4个周期。¹²⁵I粒子在化疗间期植入,中位粒子数43,处方剂量（prescribed dose,PD）120 Gy,粒子中位活度0.7 mCi （2.59×10⁷ Bq）,范围0.68~0.82 mCi （2.52×10⁷~3.03×10⁷ Bq）。患者中位随访时间48个月,观察生存率。结果 靶区瘤体周围处方剂量mPD （118.7±7.2）Gy,D₉₀（126±4.7）Gy,D₉₀> mPD。术后6个月胸部CT显示,完全缓解（CR）11例,占30.6%;部分缓解（PR）19例,占52.8%;疾病稳定（SD）5例,占13.9%;疾病进展（PD）1例,占2.8%;总有效率（CR＋PR）为83.4%,共30例。1、3、5年的局部控制率分别为92%、83%和67%,中位局部控制时间56.8个月。1、3、5年累计生存率分别为84.1%、56.7%和36.8%,中位生存期38个月。结论 化疗联合组织间近距离¹²⁵I粒子植入是一种微创有效的治疗肺上沟癌的方法。     

模拟胆管内不同弧度125I粒子链的剂量学研究

目的 研究不同弧度胆管内¹²⁵I粒子链剂量学分布情况。方法 在纸上勾画出不同弧度的粒子链模型（弧长=2πr×角度/360）,计算弧长为45 mm对应的0°、30°、60°、90°、120°、150°、180°的模型。粒子链模型总长度为45 mm（每枚粒子间距为0 mm）。在粒子链模型向心侧和离心侧的中心点及两端点垂直距离5 mm处画标尺。用激光扫描仪扫描模型。每个弧度模型创建3层图片,模拟直径为8 mm的胆管。将图片导入放射性粒子源植入治疗计划系统（TPS）,模拟不同弧度的粒子链。使用TPS勾画大体肿瘤靶区（GTV）用于模拟直径8 mm的胆管,设定粒子初始活度1.85×10⁷ Bq,给予处方剂量60 Gy。计算直径为8 mm模拟胆管的D₉₀和V₁₀₀,以及粒子链中心点、两端点的向心侧及离心侧5 mm处剂量变化情况。结果 粒子链弧度为30°时,D₉₀（132 Gy）和V₁₀₀（100%）最高;弧度为60°时,D₉₀（45 Gy）和V₁₀₀（68%）最低。弧度为30°时,中心点处剂量最高（向心侧剂量为165 Gy,离心侧剂量142 Gy）;弧度为180°时,中心点处剂量最低（向心侧剂量为90 Gy,离心侧剂量50 Gy）。不同弧度时（不含0°）,中心点向心侧剂量均高于离心侧;两端点离心侧的剂量均大于向心侧。结论 随着弧度改变,粒子链剂量分布也相应变化,30°时D₉₀、V₁₀₀最大;弧度近心侧剂量明显高于远心侧。     

Nephrotoxicity profiles and threshold dose values for [177Lu]-DOTATATE in nude mice

IntroductionIn peptide receptor radionuclide therapy for neuroendocrine tumors the main dose-limiting tissue is found in the kidneys because of tubular reabsorption and retention of radioactivity. The aim of this study was to quantify late effects in renal cortex of nude mice exposed to high amounts of [¹⁷⁷Lu]-DOTA-Tyr³-octreotate ([¹⁷⁷Lu]-DOTATATE), and to determine whether a threshold dose value exists for these findings.MethodsNude mice were exposed to 90, 120 or 150 MBq of [¹⁷⁷Lu]-DOTATATE. Renal toxicity was evaluated up to 6 months after injection. Blood samples were collected to examine renal functional markers, and after sacrifice at 6 months changes in renal morphology were explored. Tissue damage was estimated by quantifying the relative area of the different subunits in the renal cortex using point counting. Additional morphological signs of radiation damage were also noted. The absorbed doses to the kidneys were estimated by previously determined kidney pharmacokinetics and Monte Carlo simulations for different assumptions regarding the activity distribution.ResultsIncreased serum creatinine and urea values indicated long-term renal toxicity. The tissue area occupied by proximal tubules decreased with increasing doses of [¹⁷⁷Lu]-DOTATATE, whereas the other subunits in cortex slightly increased. The mean absorbed dose in the renal cortex for [¹⁷⁷Lu]-DOTATATE was estimated to be 35–58 Gy for the different groups of animals. A dose–response relationship was observed for proximal tubular damage, and a threshold dose value of 24 Gy (BED 37 Gy) was determined.ConclusionsSelective morphological changes in kidney cortex of nude mice were quantified and appeared in a dose dependent manner after injection of high amounts of [¹⁷⁷Lu]-DOTATATE.     

胶体32P-磷酸铬间质给药对犬累积损伤效应的研究

目的 探讨胶体³²P-磷酸铬(³²P-CP)在正常Beagle犬的肝叶或臀大肌行间质注射的安全性。方法 10只Beagle犬,随机分成间质给药不同剂量(185和370MBq)、不同部位(臀大肌和肝脏)及冷胶体对照5组(n＝2)。术后不同时间点称量体重,行血液生化学检查,ECT轫致辐射显像,组织形态学动态观察及连续测量体表、血液、尿液和粪便放射性计数率值。计量数据以均数±标准差(±s)表示,采用SPSS13.0软件进行统计分析。结果 给药后ECT示肝脏组全肝显影,放射性分布呈团块状不均匀,肌肉组局部放射性持续浓聚,肝脏未见显影。术后第4组犬体重进行性减少,45d时较术前减少2.7kg,余组体重增值均数依序为3.0、1.6、0.8和3.1kg。第4组血小板、红细胞术后有明显减少。分别于给药后23和45d死亡,死亡前谷草转氨酶和谷丙转氨酶均有急剧升高;其余组间血液和血生化学差异无统计学意义。术后体表分区测定以注射部位放射性计数率值为最高,其次为膀胱、脾。肝脏组血液峰时为5min,峰值分别为0.5×10⁷/min和1.0×10⁷/min;肌肉组持续在3×10⁵/min左右。组织学表现肌肉组和肝脏185MBq组4周内有充血水肿改变,8周后组织结构恢复正常;肝脏370MBq组4周内部分肝细胞坏死,6周时见大量肝细胞气球样变,充血水肿明显,肝小叶结构不清。尿液、粪便中放射性计数率肌肉组峰时均数分别为13和12d,峰值为(42.0±3.3)×10⁴/min和(29.6±4.5)×10⁴/min;肝脏组峰时为5和9d,峰值为(49.0±10.2)×10⁴/min和(28.5±7.1)×10⁴/min。至30d肌肉组从尿液和粪便中累积排泄率为36.58%和10.62%,肝脏组为23.48%和8.76%。吸收剂量肝脏组肝脏为(30.6±2.3)、(55.6±4.4)Gy;肌肉组肌肉注射部位为(53.4±3.1)、(98.1±3.3)Gy,肝脏为(2.3±1.3)、(6.5±1.2)Gy。结论 Beagle犬肝脏间质注射794.39MBq/m²,肝脏吸收剂量为56Gy时有较强肝毒性及全身毒副作用,是其致死剂量。肌肉给药463.98～772.93MBq/m²是安全剂量范围。³²P-CP间质给药是适用于治疗凡穿刺所能到达的乏血供及中等血供实体瘤的安全手段。     

放射性核素肾动态显像中的辐射剂量计算

目的 研究在放射性核素肾动态显像中肾脏和膀胱所受到的内照射剂量。方法 建立一个双隔室链肾脏-膀胱排泄模型并推导出相关的数学表达式,模拟放射性核素肾动态显像剂被人体摄入后的转移、排泄过程,计算核素在肾脏、膀胱和人体其余组织内的总衰变数,再采用蒙特卡罗模拟的方法,计算核素衰变释放的射线在肾脏以及膀胱内产生的能量沉积,最后根据辐射的品质因数计算它们的有效剂量。结果 以 ¹³¹I-OIH和 ⁹⁹Tc^m-DTPA显像剂为例,肾脏受到的内照射剂量分别为0.058mGy/MBq(¹³¹I-OIH)和0.0054 mGy/MBq(⁹⁹Tc^m-DTPA);膀胱受到的内照射剂量分别为0.40mGy/MBq(¹³¹I-OIH)和0.033mGy/MBq(⁹⁹Tc^m-DTPA)。结论 常规剂量水平下的放射性核素肾动态显像对肾脏和膀胱造成的辐射剂量很小。     

Human radiation dosimetry of [11C]MeAIB, a new tracer for imaging of system A amino acid transport

Purpose [N-methyl-¹¹C]α-methylaminoisobutyric acid ([¹¹C]MeAIB) is a promising positron emission tomography (PET) tracer for imaging hormonally regulated system A amino acid transport. Uptake of [¹¹C]MeAIB is totally specific for amino acid transport since [¹¹C]MeAIB is metabolically stable both extra- and intracellularly. The aim of this study was to measure cumulated radioactivity in different organs and estimate the absorbed radiation doses to humans with the Medical Internal Radiation Dosimetry (MIRD) method.Methods Radiation absorbed doses were calculated from PET images for 25 volunteers. Dynamic acquisition data were obtained for the thoracic, abdominal, femoral and head and neck regions. The median dose of intravenously injected [¹¹C]MeAIB was 422±35 MBq, with a range of 295–493 MBq. After PET imaging the radioactivity in voided urine was measured. Experimental human data were used for residence time estimates. Radiation doses were calculated with commonly used software.Results The effective dose for a 70-kg adult was 0.004 mSv/MBq, corresponding to a 1.72 mSv effective dose from the PET study with injection of 430 MBq [¹¹C]MeAIB. The highest absorbed doses were in the pancreas (0.018 mGy/MBq), kidneys (0.017 mGy/MBq), intestine (0.014 mGy/MBq), liver (0.008 mGy/MBq) and stomach (0.005 mGy/MBq). Only 0.57% of injected activity was excreted to urine within 1 h after injection.Conclusion Biodistribution of [¹¹C]MeAIB in the abdominal region reflected the high activity of the transportation of amino acids via system A and these organs also had the highest radiation doses. An effective dose of 0.004 mSv/MBq is fully justified when [¹¹C]MeAIB PET is performed to study system A activity in vivo.     

Pre-dosing with lilotomab prior to therapy with <Superscript>177</Superscript>Lu-lilotomab satetraxetan significantly increases the ratio of tumor to red marrow absorbed dose in non-Hodgkin lymphoma patients

Purpose

¹⁷⁷Lu-lilotomab satetraxetan is a novel anti-CD37 antibody radionuclide conjugate for the treatment of non-Hodgkin lymphoma (NHL). Four arms with different combinations of pre-dosing and pre-treatment have been investigated in a first-in-human phase 1/2a study for relapsed CD37+ indolent NHL. The aim of this work was to determine the tumor and normal tissue absorbed doses for all four arms, and investigate possible variations in the ratios of tumor to organs-at-risk absorbed doses.

Methods

Two of the phase 1 arms included cold lilotomab pre-dosing (arm 1 and 4; 40 mg fixed and 100 mg/m² BSA dosage, respectively) and two did not (arms 2 and 3). All patients were pre-treated with different regimens of rituximab. The patients received either 10, 15, or 20 MBq ¹⁷⁷Lu-lilotomab satetraxetan per kg body weight. Nineteen patients were included for dosimetry, and a total of 47 lesions were included. The absorbed doses were calculated from multiple SPECT/CT-images and normalized by administered activity for each patient. Two-sided Student’s t tests were used for all statistical analyses.

Results

Organs with distinct uptake of ¹⁷⁷Lu-lilotomab satetraxetan, in addition to tumors, were red marrow (RM), liver, spleen, and kidneys. The mean RM absorbed doses were 0.94, 1.55, 1.44, and 0.89 mGy/MBq for arms 1–4, respectively. For the patients not pre-dosed with lilotomab (arms 2 and 3 combined) the mean RM absorbed dose was 1.48 mGy/MBq, which was significantly higher than for both arm 1 (p?=?0.04) and arm 4 (p?=?0.02). Of the other organs, the highest uptake was found in the spleen, and there was a significantly lower spleen absorbed dose for arm-4 patients than for the patient group without lilotomab pre-dosing (1.13 vs. 3.20 mGy/MBq; p?<?0.01).Mean tumor absorbed doses were 2.15, 2.31, 1.33, and 2.67 mGy/MBq for arms 1–4, respectively. After averaging the tumor absorbed dose for each patient, the patient mean tumor absorbed dose to RM absorbed dose ratios were obtained, given mean values of 1.07 for the patient group not pre-dosed with lilotomab, of 2.16 for arm 1, and of 4.62 for arm 4. The ratios were significantly higher in both arms 1 and 4 compared to the group without pre-dosing (p?=?0.05 and p?=?0.02). No statistically significant difference between arms 1 and 4 was found.

Conclusions

RM is the primary dose-limiting organ for ¹⁷⁷Lu-lilotomab satetraxetan treatment, and pre-dosing with lilotomab has a mitigating effect on RM absorbed dose. Increasing the amount of lilotomab from 40 mg to 100 mg/m² was found to slightly decrease the RM absorbed dose and increase the ratio of tumor to RM absorbed dose. Still, both pre-dosing amounts resulted in significantly higher tumor to RM absorbed dose ratios. The findings encourage continued use of pre-dosing with lilotomab.

     

Long-term toxicity of [<Superscript>177</Superscript>Lu-DOTA<Superscript>0</Superscript>,Tyr<Superscript>3</Superscript>]octreotate in rats

Purpose and methods Studies on peptide receptor radionuclide therapy (PRRT) using radiolabelled somatostatin analogues have shown promising results with regard to tumour control. The efficacy of PRRT is limited by uptake and retention in the proximal tubules of the kidney, which might lead to radiation nephropathy. We investigated the long-term renal toxicity after different doses of [¹⁷⁷Lu-DOTA⁰,Tyr³]octreotate and the effects of dose fractionation and lysine co-injection in two tumour-bearing rat models. Results Significant renal toxicity was detected beyond 100 days after start of treatment as shown by elevated serum creatinine and proteinuria. Microscopically, tubules were strongly dilated with flat epithelium, containing protein cylinders. Creatinine levels rose significantly after 555 MBq [¹⁷⁷Lu-DOTA⁰,Tyr³]octreotate, but were significantly lower after 278 MBq (single injection) or two weekly doses of 278 MBq. Renal damage scores were maximal after 555 MBq and significantly lower in the 278 and 2×278 MBq groups. Three doses of 185 MBq [¹⁷⁷Lu-DOTA⁰,Tyr³]octreotate with intervals of a day, a week or a month significantly influenced serum creatinine (469±18, 134±70 and 65±15 μmol/l, respectively; p<0.001). Renal histological damage scores were not significantly influenced by dose fractionation. Lysine co-administration with three weekly treatments of 185 MBq significantly lowered serum creatinine and proteinuria. Conclusion Injection of high doses of [¹⁷⁷Lu-DOTA⁰,Tyr³]octreotate resulted in severe renal damage in rats as indicated by proteinuria, elevated serum creatinine and histological damage. This damage was dose dependent and became overt between 100 and 200 days after treatment. Dose fractionation had significant beneficial effects on kidney function. Also, lysine co-injection successfully prevented functional damage.     

Radiation dosimetry of <Emphasis Type="Italic">N</Emphasis>-([<Superscript>11</Superscript>C]methyl)benperidol as determined by whole-body PET imaging of primates

Purpose N-([¹¹C]methyl)benperidol ([¹¹C]NMB) can be used for positron emission tomography (PET) measurements of D₂-like dopamine receptor binding in vivo. We report the absorbed radiation dosimetry of i.v.-administered ¹¹C-NMB, a critical step before applying this radioligand to imaging studies in humans. Materials and methods Whole-body PET imaging with a CTI/Siemens ECAT 953B scanner was done in a male and a female baboon. After i.v. injection of 444–1221 MBq of ¹¹C-NMB, sequential images taken from the head to the pelvis were collected for 3 h. Volumes of interest (VOIs) were identified that entirely encompassed small organs (whole brain, striatum, eyes, and myocardium). Large organs (liver, lungs, kidneys, lower large intestine, and urinary bladder) were sampled by drawing representative regions within the organ volume. Time–activity curves for each VOI were extracted from the PET, and organ residence times were calculated by analytical integration of a multi-exponential fit of the time–activity curves. Human radiation doses were estimated using OLINDA/EXM 1.0 and the standard human model. Results Highest retention was observed in the blood and liver, each with total residence times of 1.5 min. The highest absorbed radiation doses were to the heart (10.5 mGy/kBq) and kidney (9.19 mGy/kBq), making these the critical organs for [¹¹C]NMB. A heart absorption of 50 mGy would result from an injected dose of 4,762 MBq [¹¹C]NMB. Conclusions Thus, this study suggests that up to 4,762 MBq of [¹¹C]NMB can be safely administered to human subjects for PET studies. Total body dose and effective dose for [¹¹C]NMB are 2.82 mGy/kBq and 3.7 mSv/kBq, respectively.     

Biodistribution and dosimetry of iodine-123-labelled Z -MIVE: an oestrogen receptor radioligand for breast cancer imaging

This study reports on the distribution and radiation dosimetry of iodine-123-labelled cis-11β-methoxy-17α-iodovinyloestradiol (Z-[¹²³I]MIVE), a promising radioligand for imaging of oestrogen receptors (ERs) in human breast cancer. Whole-body scans were performed up to 24 h after intravenous injection of 138–193 MBq Z-[¹²³I]MIVE in five healthy female volunteers, four with and one without thyroid blockade. Blood samples were taken at various times up to 24 h after injection. Urine was collected up to 24 h after injection in order to calculate renal clearance and to aid in the interpretation of whole-body clearance, including faecal excretion. Time-activity curves were generated for the thyroid, heart, brain, breasts and liver, by fitting the organ-specific geometric mean counts, obtained from regions of interest, to a multicompartmental model. The MIRD formulation, using 11 source organs, was applied to calculate the absorbed radiation doses for various organs upon administration of Z-[¹²³I]MIVE. The images showed rapid hepatobiliary excretion which resulted in good imaging conditions for the thoracic region. Imaging of the abdominal region was impeded due to extensive bowel activity. Diffuse uptake and retention of activity was seen in breast tissue, the breast-to-non-specific uptake ratio increasing over time. Z-[¹²³I]MIVE was cleared by both the kidneys and the gastrointestinal tract. At 50 h p.i. the mean excretion in urine was predicted to be 58%±14% (SD) and that in faeces 31%±19%. If the thyroid was not blocked, it was the most critical organ (0.33 mGy/MBq). In general, the excretory organs received the highest absorbed doses, i.e. the lower and upper large intestinal walls (0.11 and 0.098 mGy/MBq, respectively), the urinary bladder wall (0.090 mGy/MBq), the gallbladder wall (0.087 mGy/MBq) and the small intestine (0.043 mGy/MBq). The average effective dose equivalent of Z-[¹²³I]MIVE was estimated to be 0.033 mSv/MBq. The amount of Z-[¹²³I]MIVE required for adequate breast cancer ER imaging results in an acceptable effective dose equivalent to the patient. Received 28 June and in revised form 26 September 1997     

Dosimetric analysis of chimeric monoclonal antibody cMOv18 IgG in ovarian carcinoma patients after intraperitoneal and intravenous administration

In this study the potential of intraperitoneal (i.p.) and intravenous (i.v.) administration of chimeric iodine-131-labelled MOv18 IgG for radioimmunotherapy was determined. The dosimetry associated with both routes of administration of cMOv18 IgG was studied in patients. Eight patients suspected of having ovarian carcinoma received 150 MBq ¹³¹I-cMOv18 IgG i.p. Blood and urine were collected and serial gamma camera images were acquired. Another group of four patients received 7.5 MBq ¹³¹I-cMOv18 IgG i.v. For all patients, tissue biopsies were obtained at surgery. Activity in the blood after i.p. administration was described by a bi-exponential curve with a mean uptake and elimination half-life of 6.9±3.2 h and 160±45 h, respectively. For i.v. infusion the mean half-life for the elimination phase was 103±12 h. Cumulative excretion in the urine was 17%±3% ID and 21%±7% ID in 96 h for i.p. and i.v. administration, respectively. Scintigraphic images after i.p. administration showed accumulation in ovarian cancer lesions, while all other tissues showed decreasing activity with time. Tumour uptake determined in the ovarian cancer tissue specimens ranged from 3.4% to 12.3% ID/kg for i.p. administration and from 3.6% to 5.4% ID/kg for i.v. administration. Dosimetric analysis of the data indicated that 1.7–4.3 mGy/MBq and 1.7–2.2 mGy/MBq can be guided to solid or ascites cells after i.p. and i.v. administration, respectively. Assuming that an absorbed dose to the bone marrow of 2 Gy will be dose limiting, a total activity of 4.1 GBq ¹³¹I-cMOv18 IgG can be administered safely via the i.p. route and 3.5 GBq via the i.v. route. At this maximal tolerated dose, a maximum absorbed dose to 1-g tumours in the peritoneal cavity of 18 and 8 Gy can be reached after i.p. and i.v. administration, respectively. For the i.p. route of administration, dose estimates for the tumour are even higher when the electron dose of the peritoneal activity is also taken into account: total doses to the tumour of 30 Gy and 22 Gy will be absorbed at the tumour surface and at 0.2 mm depth, respectively. In conclusion, therapeutic tumour doses can be achieved with ¹³¹I-cMOv18 IgG in patients with intraperitoneal ovarian cancer lesions with no normal organ toxicity. The i.p. route of administration seems to be preferable to i.v. administration. Received 10 July and in revised form 17 August 1998