~(131)I-美妥昔单抗联合动脉化疗栓塞治疗原发性肝癌的药代动力学研究

目的 探讨~(131)I-美妥昔单抗联合动脉化疗栓塞(TACE)治疗原发性肝癌(HCC)的药代动力学.方法 15例肝癌患者巴塞罗纳临床肝癌分期(BCLC、B期7例、C期8例),经肝动脉注入~(131)I-美妥昔单抗(27.75 MBq/kg),间隔20 min后再注入混合化疗药物的碘化油乳剂.γ计数仪测量注射药物后5 min和0.5、2.0、4.0、24.0、48.0、72.0、120.0、168.0 h血清和尿液的放射性浓度,拟合血液药物放射性-时间曲线,残数法计算药物动力学参数和尿液药物清除速率.用SPECT行4次不同时间的全身扫描,使用ROI图像处理法计算肝肿瘤与非肿瘤组织放射性比值(T/NT),依据医学内照射辐射剂量学方法计算器官的内照射吸收剂量,采用重复测量资料的方差分析对患者体内不同时间各组织器官之间的~(131)I-美妥昔单抗分布以及T/NT值进行统计检验.结果 ~(131)I-美妥昔单抗联合TACE治疗HCC的药代动力学符合二室开放模型,药物体内吸收半衰期(t_(1/2)α)为(1.96±1.65)h,分布半衰期(t_(1/2)α)为(19.07±5.91)h,消除半衰期(t_(1/2)β)为(57.09±10.92)h,血药峰值浓度(C_(max)为2.113×10~9min~(-1)·L~(-1),血液药物放射性-时间曲线下面积(AUC_(0-∞))为1.302×10~(11)h·min~(-1)·L~(-1).用药1周累积尿排泄放射性占注入剂量的52.2%.患者体内不同时间各组织器官之间的~(131)I-美妥昔单抗分布以及T/NT值差异有统计学意义(F值分别=6.583、3.546,P值均<0.01);器官放射性分布主要浓聚于肝区肿瘤组织,心脏和脾脏等其他组织分布少.肝脏T/NT值呈逐渐减少趋势,3 h为2.88±1.02,至168 h为1.64±0.40.器官吸收剂量分别为肝脏(3.19±1.01)Gy,红骨髓(0.55±0.09)Gy.结论 ~(131)I-美妥昔单抗联合TACE治疗HCC可提高~(131)I-美妥昔单抗的肿瘤靶向性,保证患者的辐射安全.     

131I标记抗肝癌单克隆抗体片段的内照射吸收剂量估算

目的对给予^131I标记抗肝癌单克隆抗体（简称单抗）片段[HAb18F（ab）2]的志愿者进行脏器内照射吸收剂量估算。方法2例志愿者静脉注射^131I-HAbl8F（ab）2后，分别于5、30min和2、4、8、24h及2、3、4、6、10d共11个时间点收集血样，并分别于治疗后3、24h和2、4、8、16d进行SPECT全身显像；对血样进行放射性测量，测定全身平面图像感兴趣区（ROI）计数；应用SPSS13．0软件对获得的数据进行曲线拟合；计算药物在各脏器的有效半衰期；估算各脏器的吸收剂量。结果^131I-HAb18F（ab）2在人体各脏器内的有效半衰期为1．8～6．4d，甲状腺的吸收剂量最大为28．5Gy，其余脏器不超过3Gy。结论该计算方法简便易行，可应用于内照射吸收剂量的估算。     

131I-肿瘤细胞核人鼠嵌合单抗肿瘤治疗内照射吸收剂量估算

目的　估算1 31 I 肿瘤细胞核人鼠嵌合单克隆抗体 (chTNT)肿瘤治疗中肿瘤和主要器官内照射吸收剂量。方法　 9例肿瘤患者 ,单次静脉注射1 31 I chTNT按体重 (2 9 6± 3 7)MBq kg后测量各时间点血、尿样放射性 ,并采用连续 (配对 )显像结合CT扣除周围组织本底的方法估算各时间点全身、肿瘤及主要器官放射性 ;将原始数据转换为百分注射剂量 (%ID) ,用一室或二室模型拟合时间 放射性曲线 ,求单位累积活度 ,采用医用内照射照射吸收剂量 (MIRD)方法将其输入Mirdose 3软件 ,求得全身、肿瘤和各主要器官的平均总吸收剂量。结果　肿瘤平均总吸收剂量为 (8 2 8± 2 6 5 )Gy ,瘤 非瘤比值为 3 95± 1 5 5。结论　该注射剂量难以满足抑制肿瘤生长的要求。为姑息性抑制肿瘤生长 ,有必要多次重复给药。     

药盒法制备99mTc-RBC的人体内稳定性及内照射剂量研究

目的研究用自制RBC药盒制备的^99mTc—RBC人体内稳定性和内照射辐射吸收剂量。方法4名健康志愿者，分别取肘静脉血1ml，用自制的RBC药盒进行放射性锝标记，每人注射481～555MBq，给药后5min，1，2．5，4，8和24h进行全身显像，测定^99Tc-RBC在人体内的生物分布；计算各器官在各时间点的放射性占注入量的百分数（％ID）；两种方法绘制各脏器时间一放射性计数曲线，计算各脏器的滞留时间，用MIRDOSE3．0软件计算出各受照器官的内照射辐射剂量。结果^99Tc—RBC在人体内较稳定，血池及大血管于给药后5min至8h均可清晰显影；人体内照射辐射吸收剂量估算结果与文献值相近，按一次给药555MBq计算，各器官的吸收剂量均低于50mGy。结论用本实验室自制RBC药盒制备的^99Tc—RBC体内稳定性好，内照射辐射吸收剂量符合要求。     

内照射剂量学指导131I治疗分化型甲状腺癌弥散性肺转移

目的 从内照射剂量学角度探讨如何确定治疗分化型甲状腺癌弥散性肺转移（DTC-DPM）的131I活度.方法 依据美国核医学会医用内照射剂量学委员会提出的内照射剂量计算方法（MIRD体系）,将131I治疗DTC-DPM服131I后48 h时滞留于患者体内的131I不超过2.96 GBq的限定（2.96 GBq法则）转变为服131I后48 h时肺组织剂量率限定（DRCLU·48h）.假设眼131I后48 h时沉积于肺的131I与滞留于全身的131I活度比（F48h）在0.6～0.9间,131I在肺及剩余组织的有效半衰期（TLL、TRB）分别为20～120 h和10～20 h,参照OLINDA（Organ Level Internal Dose Assessment）软件中不同参考人体数据,计算不同DTC-DPM患者的131Ⅰ最大安全治疗活度（Amax）.结果 依据MIRD体系和2.96 GBq法则,131I治疗DTC-DPM,DRCLU·48h应不超过46.4 mGy/h.按照不同的F48h、TLU及TRB,成年男性、成年女性、15岁和10岁DTC-DPM患者的Amax分别在6.77～81.36 GBq、5.29～56.20 GBq、5.08～55.19 GBq和3.87～40.52 GBq间.结论 内照射剂量学指导131I治疗DTC-DPM充分地考虑了131I在不同患者体内的代谢动力学差异,可在避免发生放射性肺炎、肺纤维化的前提下,调节131I用量.     

153Sm-EDTMP吸收剂量的MonteCarlo和MIRD算法比较

目的以153Sm-乙二胺四甲撑膦酸(153Sm-EDTMP)治疗鼻咽癌多发性骨转移为例,分别用蒙特卡罗法(Monte Carlo,MC)和MIRD方法计算153Sm-EDTMP治疗后病灶和骨髓等靶器官的吸收剂量,探讨其临床应用之不同.方法基于病人时序性SPECT/CT扫描和累积尿液的放射性测定,利用优化的MC EGS4程序和MIRD方法分别计算病灶和其他靶器官的吸收剂量.结果MC EGS4法计算结果提示病灶内剂量分布不均匀.患者注射153Sm-EDTMP 33.6×37 MBq,左髂骨转移病灶最高吸收剂量约为5.6 Gy,病灶边缘的吸收剂量为2.0 Gy,以病灶区最高剂量点为参考点,则椎体、皮质、骨髓、脊髓和盆腔组织仅相当于最高剂量的37%、12%、13%、21%和2%;MIRD方法的计算数据仅能粗略提示全身红骨髓吸收剂量,为2.39 Gy.结论MC EGS4方法能准确计算病灶、骨髓和其他靶器官的内照射吸收剂量,故可以真正指导核素临床治疗;而MIRD仅能大致评估153Sm-EDTMP的骨髓毒性.     

分化型甲状腺癌患者^131I治疗后体内残留放射性活度的评估

目的 评估分化型甲状腺癌（DTC）患者^131I治疗后体内残留放射性活度.方法 本研究共纳入了35例DTC患者,分为“清甲”（20例）与“清灶”（15例）组,分别于服^13I后2、6、24、48、72 h进行^131I全身显像及1m处当量剂量率的测定,以2h时显像计数和活度作为总计数和总活度.根据各时间点显像计数与2h的显像计数比值间接估算体内残留放射性活度,并估算患者体内残留放射性活度达到400 MBq时的1m处当量剂量率.统计学分析采用直线相关与回归分析.结果 “清甲”组服^131I后2、6、24、48、72 h体内残留^131I活度占服^131I总活度的百分比分别为99％±4％、86％±6％、35％±10％、12％±8％、7％±8％, “清灶”组分别为99％±1％、91％±7％、47％±17％、11％±9％、4％±6％. “清甲”组服^131I后2、6、24、48、72 h的1m处当量剂量率分别为（157±37）、（120±36）、（35±13）、（11±9）、（9±11）μSv/h,“清灶”组分别为（234±43）、（186±51）、（49±20）、（12±11）、（4±6）μSv/h.体内残留的放射性活度与1m处当量剂量率呈正相关（r=0.87,P＜0.001）.“清甲”与“清灶”组服^131I后48、72 h体内残留放射性活度分别为（432±292）、（265±281） MBq及（731±701）、（277±470） MBq,对应的1m处当量剂量率为8～ 11 μSv/h.结论 DTC患者服^131I后48～72 h体内残留放射性活度达到国家标准规定的400 MBq时,即DTC患者1m处当量剂量率达到8～11 μSv/h时方可出院.     

131I-美妥昔单抗注射液的人体显像和组织分布

笔者研究了国家一类新药——^131I-美妥昔单克隆抗体[简称单抗，肝癌单抗片段HAb18F（ab’）2]注射液（批号1999XL0140）在人体的显像和分布，现报道如下。     

131I清除分化型甲状腺癌术后残留腺体的内照射吸收剂量与疗效的分析

目的 探讨131I清除DTC术后残留甲状腺组织（简称清甲）的内照射吸收剂量与疗效的相关性.方法 前瞻性分析2009年9月至2011年9月拟行清甲的72例DTC患者[男14例,女58例,年龄16～67（41±16）岁].在患者服用3.7 GBq 131I后采用连续显像法评估残留腺体的碘代动力学,利用超声测量残留腺体的质量,按照美国核医学会医用内照射剂量学委员会提出的内照射吸收剂量计算方法,计算残留腺体的吸收剂量.清甲治疗后6～9个月,判断疗效：若刺激状态下Tg＜l μg/L及颈部超声检查提示甲状腺床区无腺体组织残留,判断为清甲成功.清甲成功与未成功者组间比较采用两样本t检验.结果 72例患者的残留腺体24h摄碘率为0.9％～6.3％, 131I有效半衰期为12.0～146.4 h,腺体质量为1.0～6.9g,吸收剂量为23～2 197 Gy,24 h吸收剂量率为0.5～8.1 Gy/h.43例清甲成功者与29例清甲未成功者残留腺体的吸收剂量分别为（363±148） Gy和（341±167） Gy,差异无统计学意义（￡=15.097,P＞0.05）;24 h吸收剂量率分别为（3.7±2.1） Gy/h和（2.9±1.6） Gy/h,差异有统计学意义（t=7.908,P＜0.05）.结论 131I清甲残留腺体的吸收剂量率影响清甲疗效.     

^131I-酪氨酸-奥曲肽对荷人非小细胞肺癌小鼠的抑瘤效果

目的探讨^131I标记酪氨酸一奥曲肽（^131I-Tyr-octreotide）对荷人非小细胞肺癌（NSCLC）小鼠的抑瘤效果。方法经氯胺T法标记Tyr-octreotide,测其放化纯及其在小鼠体内的生物分布;建立荷人NSCLC小鼠模型,分为尾静脉注射^131I-Tyr-octreotide组、肿瘤间质注射^131I-Tyr-octreotide组、肿瘤间质单纯注射^131I组和间质注射生理盐水组,观察肿瘤部位的放射性摄取,勾画感兴趣区（ROI）,计算肿瘤与对侧正常组织（T／NT）放射性比值,并对肿瘤进行细胞周期检测和免疫组织化学检测,观察癌细胞的凋亡。采用SPSS 11.0软件进行统计学处理,组间两两比较行单因素方差分析。结果标记产物放化纯为（95．23±1．67）％,比活度为3．5×10^6 Bq／μg。小鼠体内放射性分布示肾摄取最高,肝、脾摄取较少;荷瘤鼠显像示：间质注射^131I-Tyr-octreotide组肿瘤放射性浓聚较尾静脉注射和间质单纯注射^131I明显,放射性滞留较久;其24h的T／NT比值最高,为52．74±0．13,明显高于其他2组（8．90±0．23,6．42±0．02,q=628．81和664．33,P均〈0．05）;流式细胞检测可见经间质给药组较尾静脉给药组和单纯注射^131I组G．期细胞阻滞明显[各组G1期肿瘤细胞占总细胞的百分比分别为（83．17±6．86）％、（57．02±18．81）％、（49．29±7．80）％,q=1．56～6．86,P均〈0．05],免疫组织化学检查结果示肿瘤细胞大量凋亡,可见凋亡小体形成。结论^131I-Tyr-octreotide易于标记且与生长抑素受体（SSTR）表达阳性的NSCLC有较高的亲和力,对肿瘤组织有较强的促凋亡和抑瘤作用。     

Radioisotope therapy of malignant pheochromocytoma with iodine-131 metaiodobenzylguanidine--absorbed dose assessments using SPECT]

The correlation of absorbed doses D (rad) of tumors in 4 patients with malignant pheochromocytoma, who were treated by 131I-MIBG (3.7 GBq), with their clinical courses were analyzed and the clinical significance of determination of absorbed dose was discussed. Absorbed doses of 131I-MIBG in the tumors were measured by using SPECT at the time of therapy. Absorbed dose was calculated based on the MIRD (medical internal radiation dose committee) equation. Tumor volumes were ranged from 17 g-100 g (mean 40 g), effective half lives were ranged from 1.3 days-5.9 days (mean 3.6 days), and tumor absorbed doses were varied between 5.4 Gy-68 Gy (mean 40 Gy). When the absorbed doses of the tumor exceeded over 40 Gy, good clinical responses were obtained. The initial treatment seemed to be important for 131I-MIBG therapy, since the absorbed doses in the following therapy became reduced. These results indicate that the quantitative SPECT for radioisotope therapy is clinically valid and that the calculated absorbed doses correlate well with clinical responses.     

Bone marrow dosimetry and safety of high 131I activities given after recombinant human thyroid-stimulating hormone to treat metastatic differentiated thyroid cancer.

Recombinant human thyroid-stimulating hormone (rhTSH) recently was introduced as a radioiodine administration adjunct that avoids levothyroxine (LT-4) withdrawal and resultant hypothyroidism. The pharmacokinetics of 131I after rhTSH administration are known to differ from those after LT-4 withdrawal but are largely nondelineated in the radioiodine therapy setting. We therefore sought to calculate the red marrow absorbed dose of high therapeutic activities of 131I given after rhTSH administration to patients with metastatic or inoperable locally recurrent differentiated thyroid cancer. We also sought to evaluate the clinical and laboratory effects of this therapy on the bone marrow. METHODS: Fourteen consecutive patients received in total 17 131I treatments (7.4 GBq). Blood and urine samples were obtained at fixed intervals, and their activities were measured in a well counter. Based on blood activity, renal clearance of the activity, and residence times in red marrow and the remainder of the body, the red marrow absorbed dose was calculated using the MIRD schema. Additionally, we monitored for potential hematologic toxicity and compared platelet counts before and 3 mo after treatment. RESULTS: The mean +/- SD absorbed dose per unit of administered (131)I in the red marrow was 0.16 +/- 0.07 mGy/MBq. The corresponding total red marrow absorbed dose was 1.15 +/- 0.52 Gy (range, 0.28-1.91 Gy). In none of the patients was hematologic toxicity observed. The mean +/- SD platelet count (n = 13 treatments) was 243 +/- 62 x 10(9)/L before treatment and 233 +/- 87 x 10(9)/L 3 mo later, a slight and statistically insignificant decrease. After rhTSH-aided administration of high activities of 131I, the bone marrow absorbed dose remained under 2 Gy, the level long considered the safety threshold for all radioiodine therapy. CONCLUSION: Our specific findings imply that when clinically warranted, rhTSH should allow an increase in the therapeutic radioiodine activity. Such an increase might improve efficacy while preserving safety and tolerability; this possibility should be assessed in further studies.     

High-dose (131)I-tositumomab (anti-CD20) radioimmunotherapy for non-Hodgkin's lymphoma: adjusting radiation absorbed dose to actual organ volumes.

Radioimmunotherapy (RIT) using (131)I-tositumomab has been used successfully to treat relapsed or refractory B-cell non-Hodgkin's lymphoma (NHL). Our approach to treatment planning has been to determine limits on radiation absorbed dose to critical nonhematopoietic organs. This study demonstrates the feasibility of using CT to adjust for actual organ volumes in calculating organ-specific absorbed dose estimates. METHODS: Records of 84 patients who underwent biodistribution studies after a trace-labeled infusion of (131)I-tositumomab for RIT (January 1990 and April 2003) were reviewed. Serial planar gamma-camera images and whole-body NaI probe counts were obtained to estimate (131)I-antibody source-organ residence times as recommended by the MIRD Committee. The source-organ residence times for standard man or woman were adjusted by the ratio of the MIRD phantom organ mass to the CT-derived organ mass. RESULTS: The mean radiation absorbed doses (in mGy/MBq) for our data using the MIRD model were lungs = 1.67; liver = 1.03; kidneys = 1.08; spleen = 2.67; and whole body = 0.3; and for CT volume-adjusted organ volumes (in mGy/MBq) were lungs = 1.30; liver = 0.92; kidneys = 0.76; spleen = 1.40; and whole body = 0.22. We determined the following correlation coefficients between the 2 methods for the various organs: lungs, 0.49 (P = 0.0001); liver, 0.64 (P = 0.004); kidneys, 0.45 (P = 0.0004); spleen, 0.22 (P = 0.0001); and whole body, 0.78 (P = 0.0001), for the residence times. For therapy, patients received mean (131)I administered activities of 19.2 GBq (520 mCi) after adjustment for CT-derived organ mass compared with 16.0 GBq (433 mCi) that would otherwise have been given had therapy been based only using standard MIRD organ volumes-a statistically significant difference (P = 0.0001). CONCLUSION: We observed large variations in organ masses among our patients. Our treatments were planned to deliver the maximally tolerated radiation dose to the dose-limiting normal organ. This work provides a simplified method for calculating patient-specific radiation doses by adjusting for the actual organ mass and shows the value of this approach in treatment planning for RIT.     

Estimates of radiation absorbed dose for intraperitoneally administered iodine-131 radiolabeled B72.3 monoclonal antibody in patients with peritoneal carcinomatoses

Using a newly available model for determining estimates of radiation absorbed dose of radioisotopes administered intraperitoneally, we have calculated absorbed dose to tumor and normal tissues based on a surgically controlled study of radiolabeled antibody distribution. Ten patients with peritoneal carcinomatosis received intraperitoneal injections of the murine monoclonal antibody B72.3 radiolabeled with 131I. Biodistribution studies were performed using nuclear medicine methods until laparotomy at 4-14 days after injection. Surgical biopsies of normal tissues and tumor were obtained. The marrow was predicted to be the critical organ, with maximum tolerated dose [200 rad (2 Gy) to marrow] expected at about 200 mCi (7.4 GBq). In patients with large intraperitoneal tumor deposits, the tumor itself is an important source tissue for radiation exposure to normal tissues. Local "hot-spots" for tumor-absorbed dose were observed, with maximum tumor-absorbed dose calculated at 11,000 rad (11 Gy) per 100 mCi (3.7 GBq) administered intraperitoneal; however, tumor rad dose varied considerably. This may pose serious problems for curative therapy, especially in patients with large tumor burdens.     

Dosimetry-guided radioactive iodine treatment in patients with metastatic differentiated thyroid cancer: largest safe dose using a risk-adapted approach.

This study is a retrospective analysis of 124 differentiated thyroid cancer patients who underwent dosimetric evaluation using MIRD methodology over a period of 15 y. The objectives of the study were to demonstrate the clinical use of dosimetry-guided radioactive iodine ([RAI] (131)I) treatment and the safe and effective application of a 3-Gy bone marrow (BM) dose in patients with differentiated thyroid cancer. METHODS: Tumor and BM dose estimates were obtained. The administered activity that would deliver a maximum safe dose to the organ at risk (red BM or lungs) was determined as well as the resulting doses to the metastases. The clinical benefit of an individual RAI treatment was predicted on the basis of the dose estimates and the expected therapeutic response. Each patient's response to treatment was assessed clinically and by monitoring the hematologic profile. RESULTS: One hundred twenty-four patients underwent 187 dosimetric evaluations. One hundred four RAI treatments were performed. A complete response at metastatic deposits was attained with absorbed doses of >100 Gy. No permanent BM suppression was observed in patients who received absorbed doses of <3 Gy to BM. The maximum administered dose was 38.5 GBq (1,040 mCi) with the BM dose limitation. CONCLUSION: Dosimetry-guided RAI treatment allows administration of the maximum possible RAI dose to achieve the maximum therapeutic benefit. Estimation of tumor dose rates helps to determine the curative versus the palliative intent of the therapy.     

Radioimmunotherapy with intravenously administered 131I-labeled chimeric monoclonal antibody MOv18 in patients with ovarian cancer.

We investigated the safety and pharmacokinetics of (131)I-labeled chimeric monoclonal antibody MOv18 ((131)I-c-MOv18 IgG) in patients with ovarian cancer and the estimated radiation dose to cancer-free organs and tumor. METHODS: Three patients were injected intravenously with 3 GBq (131)I-c-MOv18. Toxicity was evaluated according to the World Health Organization toxicity scales. Blood sampling was performed for 12 wk after injection. Whole-body and SPECT imaging was performed frequently. Dose rates were obtained with a portable dose-rate measure. Quantitative activity analysis of several organs was performed with the region-of-interest technique. Absorbed doses were calculated using MIRDOSE3. RESULTS: Transient changes in hematologic profiles were seen in 2 patients. Pancytopenia developed in 1 patient; on analysis, she entered the study probably with exhausted bone marrow reserves. Nonhematologic toxicity was mild. No human antichimeric antibody responses were observed. Mean isolation time was 12 d. The plasma elimination half-life increased almost 3-fold compared with that after tracer doses of c-MOv18. Dosimetry showed mean absorbed doses of 163, 380, 276, 338, 781, and 216 cGy, for whole-body, liver, kidney, spleen, lung, and red marrow, respectively. Tumor-absorbed doses ranged from 600 to 3800 cGy. All patients achieved a stable disease state, as confirmed by CT and carcinoma-associated antigen CA 125, lasting from 2 to >6 mo. CONCLUSION: (131)I-labeled c-MOv18 can safely be given to patients with noncompromised bone marrow reserves and may have therapeutic potential particularly in patients with minimal residual disease.     

Relationship between cumulative radiation dose and salivary gland uptake associated with radioiodine therapy of thyroid cancer

AIM: To estimate the individual absorbed dose to the parotid and submandibular salivary glands in radioiodine therapy and its dependence from the previous cumulative therapy. METHODS: Fifty-five patients with differentiated thyroid carcinoma after thyroidectomy received 1-21 GBq (131)I using single activities of 1-6 GBq. The patients were stratified according to the cumulative activities into low-activity (1-2 GBq), middle-activity (3-7 GBq), and high-activity groups (9-21 GBq). The time-activity curves over the respective salivary glands were derived from multiple static calibrated images measured for each patient up to 48 h after ingestion of the radioiodine therapy capsule with a gamma camera. Manually drawn regions of interests were used to determine the background activities and the activities arising from the salivary glands. The gland volumes were determined by ultrasonography using appropriate volume models. RESULTS: The median absorbed dose per administered activity of each single parotid and submandibular gland was about 0.15 Gy.GBq (range, 0.1-0.3 Gy.GBq(-1)) and 0.48 Gy.GBq(-1) (range, 0.2-1.2 Gy.GBq(-1)), respectively. The maximum uptake of both gland types was significantly lower for the high-activity than for the low-activity groups and correlated with the mean cumulative administered activity of the activity groups. CONCLUSION: The iodine uptake of salivary glands is significantly reduced, whereas the absorbed dose per administered (131)I activity was not significantly decreased during the course of therapy. Comparing the well-known dose-effect relationships in external radiation therapy, the absorbed dose per administered (131)I activity is too low to induce comparable radiation damage, suggesting an inhomogeneous distribution of (131)I in human salivary glands.     

Lung dosimetry for radioiodine treatment planning in the case of diffuse lung metastases.

The lungs are the most frequent sites of distant metastasis in differentiated thyroid carcinoma. Radioiodine treatment planning for these patients is usually performed following the Benua-Leeper method, which constrains the administered activity to 2.96 GBq (80 mCi) whole-body retention at 48 h after administration to prevent lung toxicity in the presence of iodine-avid lung metastases. This limit was derived from clinical experience, and a dosimetric analysis of lung and tumor absorbed dose would be useful to understand the implications of this limit on toxicity and tumor control. Because of highly nonuniform lung density and composition as well as the nonuniform activity distribution when the lungs contain tumor nodules, Monte Carlo dosimetry is required to estimate tumor and normal lung absorbed dose. Reassessment of this toxicity limit is also appropriate in light of the contemporary use of recombinant thyrotropin (thyroid-stimulating hormone) (rTSH) to prepare patients for radioiodine therapy. In this work we demonstrated the use of MCNP, a Monte Carlo electron and photon transport code, in a 3-dimensional (3D) imaging-based absorbed dose calculation for tumor and normal lungs. METHODS: A pediatric thyroid cancer patient with diffuse lung metastases was administered 37 MBq of (131)I after preparation with rTSH. SPECT/CT scans were performed over the chest at 27, 74, and 147 h after tracer administration. The time-activity curve for (131)I in the lungs was derived from the whole-body planar imaging and compared with that obtained from the quantitative SPECT methods. Reconstructed and coregistered SPECT/CT images were converted into 3D density and activity probability maps suitable for MCNP4b input. Absorbed dose maps were calculated using electron and photon transport in MCNP4b. Administered activity was estimated on the basis of the maximum tolerated dose (MTD) of 27.25 Gy to the normal lungs. Computational efficiency of the MCNP4b code was studied with a simple segmentation approach. In addition, the Benua-Leeper method was used to estimate the recommended administered activity. The standard dosing plan was modified to account for the weight of this pediatric patient, where the 2.96-GBq (80 mCi) whole-body retention was scaled to 2.44 GBq (66 mCi) to give the same dose rate of 43.6 rad/h in the lungs at 48 h. RESULTS: Using the MCNP4b code, both the spatial dose distribution and a dose-volume histogram were obtained for the lungs. An administered activity of 1.72 GBq (46.4 mCi) delivered the putative MTD of 27.25 Gy to the lungs with a tumor absorbed dose of 63.7 Gy. Directly applying the Benua-Leeper method, an administered activity of 3.89 GBq (105.0 mCi) was obtained, resulting in tumor and lung absorbed doses of 144.2 and 61.6 Gy, respectively, when the MCNP-based dosimetry was applied. The voxel-by-voxel calculation time of 4,642.3 h for photon transport was reduced to 16.8 h when the activity maps were segmented into 20 regions. CONCLUSION: MCNP4b-based, patient-specific 3D dosimetry is feasible and important in the dosimetry of thyroid cancer patients with avid lung metastases that exhibit prolonged retention in the lungs.     

Therapy using labelled somatostatin analogues: comparison of the absorbed doses with 111In-DTPA-D-Phe1-octreotide and yttrium-labelled DOTA-D-Phe1-Tyr3-octreotide

OBJECTIVE: We estimated the absorbed doses for (111)In-DTPA-D-Phe(1)-octreotide and (90)Y-DOTA-D-Phe(1)-Tyr(3)-octreotide in the same patients in order to compare the potential effectiveness (tumour dose) and safety (kidney and red marrow dose) of these drugs for peptide-targeted radiotherapy of somatostatin receptor positive tumours. METHODS: Six patients with neuroendocrine tumours underwent quantitative (111)In-DTPA-D-Phe(1)-octreotide SPECT and (86)Y-DOTA-D-Phe(1)-Tyr(3)-octreotide PET scan at intervals of 1 week. All studies were performed with a co-infusion of amino acids for renal protection. PET and SPECT were reconstructed using iterative algorithms, incorporating attenuation and scatter corrections. Tissue uptakes (IA%) were measured and used to calculate residence times. Absorbed doses to tissues were estimated and the maximal allowed activity, defined as either the activity delivering 23 Gy to the kidneys (MAA(K)) or 2 Gy to the red marrow (MAA(RM)), was calculated and the resulting tumour absorbed doses were computed. RESULTS: For the MAA(K) the mean absorbed dose to the red marrow was lower for (90)Y-DOTA-D-Phe(1)-Tyr(3)-octreotide than for (111)In-DTPA-D-Phe(1)-octreotide (1.8+/-0.9 Gy vs. 6.4+/-1.6 Gy; P<0.001). The median absorbed dose to tumours for the MAA(K) was two-fold higher for (90)Y-DOTA-D-Phe(1)-Tyr(3)-octreotide as compared to (111)In-DTPA-D-Phe(1)-octreotide (30.1 vs. 12.6 Gy; P<0.05). The median absorbed dose to tumours estimated for the MAA(RM) was 10-fold higher for (90)Y-DOTA-D-Phe(1)-Tyr(3)-octreotide than for (111)In-DTPA-D-Phe(1)-octreotide (35.1 Gy vs. 3.9 Gy; P<0.05). CONCLUSIONS: This direct intra-patient comparison confirms that the use of (90)Y-DOTA-D-Phe(1)-Tyr(3)-octreotide is more appropriate for therapy of somatostatin receptor bearing tumours. When using (111)In-DTPA-D-Phe(1)-octreotide, the red marrow represents the major critical organ; this can result in significant toxicity if high activities have to be administered to obtain efficient tumour irradiation.