99 Tcm-HYNIC-Annexin V荷瘤小鼠肿瘤细胞凋亡显像研究

目的研究99Tcm-联肼尼克酰胺-膜联蛋白V(HYNIC-Annexin V)的制备及其在荷瘤小鼠体内生物分布特性和活体显像.方法用双功能螯合剂法,以99Tcm标记Annexin V,经高效液相色谱仪分离纯化并检测产物的标记率、放化纯及稳定性.建立荷S180肉瘤小鼠模型,于20～25g/只昆明种小白鼠右前腋皮下接种S180肉瘤细胞1周.荷瘤小鼠在环磷酰胺腹膜内化疗72h后,尾静脉注射7.4 MBq(200μl)99Tcm-HYNIC-Annexin V,分别于5、30min和1、3、6 h进行显像和体内生物分布测定.实验结果应用SPSS 12.0统计软件进行分析.结果 99Tcm-HYNIC-Annexin V的标记率达95%,放化纯为99%.荷瘤小鼠注射99Tcm-HYNIC-Annexin V后6 h显像,可见肿瘤组织放射性浓聚明显异常.体内生物分布实验示,注射显像剂后6 h肿瘤组织的放射性摄取最高[每克组织百分注射剂量率(%ID/g)为1.59±0.44],与其他时相比较,差异有显著性(P＜0.05).99Tcm-HYNIC-Annexin V主要浓聚于肾、肺和肝,经肾脏排泄;其在血液中清除速度快,注射后30 min,血液放射性摄取[(1.59±0.50)%ID/g]较注射后5 min时[(8.85±2.65)%ID/g]减少80%(P＜0.05).注射显像剂后6 h,肿瘤/肌肉放射性摄取比值(3.73±1.42)高于肿瘤/血液(2.80±0.54).结论 99Tcm-HYNIC-Annexin V活体细胞凋亡显像可应用于荷瘤小鼠模型,其临床应用有待进一步研究.     

99Tcm标记双半胱氨酸-脱氧葡萄糖的小鼠实验研究

目的研究^99Tc^m标记双半胱氨酸一脱氧葡萄糖(EGDG)在正常小鼠及荷S180肉瘤小鼠体内的分布规律。方法正常小鼠及荷S180肉瘤小鼠各铝只，分8组，实验前禁食。尾静脉注射^99Tc^m-EC-DG后计算不同时间在小鼠体内的分布及肿瘤与血液、肌肉、肺、肝的放射性比值。同时，取荷瘤小鼠5只，在注射后不同时间进行显像，计算T／NT比值。结果肿瘤组织与血液、肌肉、肺的放射性比值随时间延长逐渐上升，在4h都超过1．0。显像示随时间延长瘤体周围组织放射性逐渐下降，瘤体在4h时显影清晰。结论^99Tc^m-EC-DG可用于肿瘤的葡萄糖代谢显像。     

99Tcm-环丙沙星炎症显像的动物实验研究

目的 用99Tcm标记环丙沙星并评估其生物学性能.方法 制备99Tcm-环丙沙星,测定其稳定性,并研究其在健康昆明小鼠体内和在炎症模型昆明小鼠及新西兰兔体内的分布.结果 99Tcm-环丙沙星标记率＞90%,6 h内放化纯均＞98%.99Tcm-环丙沙星静脉注射后主要分布在血供丰富的器官,如肾、肝、脾中.血液清除快,主要经泌尿系统排泄.新西兰兔炎症模型显像表明:注射99Tcm-环丙沙星1 h后即可显影;给药后3 h为炎症小鼠模型最佳显像时间,此时炎症组织/肌肉放射性比值为5.76.99Tcm-环丙沙星能高度特异地浓聚于细菌性炎症病灶.结论 99Tcm-环丙沙星是早期诊断细菌性炎症的一种特异性显像剂,其临床应用前景较好.     

^99Tc^m标记亲肿瘤三肽的实验研究

目的 进行99Tcm-精氨酸-谷氨酸-丝氨酸（RES）的亲肿瘤实验研究.方法 采用标准Fmoc固相合成法合成RES,在不同的试剂和温度（100 ℃或室温）条件下,以氯化亚锡为还原剂进行RES的99Tcm标记,优化标记条件.进行荷A549肺癌裸鼠99Tcm-RES显像并测定%ID/g,研究99TcmRES在荷瘤裸鼠体内的分布.比较兔炎性反应和肿瘤模型显像结果.结果 （1）酒石酸钠及氢氧化钠为缓冲剂,氯化亚锡为还原剂,100 ℃水浴10 min,RES放化纯最高达到85%;99Tcm-RES性能稳定,室温下放置6 h,放化纯仍达75%.（2）注射后0.5 h,99Tcm-RES多分布于心、肝、肾等血供丰富脏器,2 h血液的放射性（0.36%ID/g）降幅明显,仅相当于0.5 h（2.35%ID/g）的1/7;心、肝、肺的放射性降幅稍慢,但明显快于肿瘤;注射后0.5 h肿瘤放射性摄取为2.32%ID/g,6 h为1.54%ID/g,6 h后仍有超过60%的放射性滞留.99Tcm-RES注射后6 h肿瘤/血、肿瘤/心、肿瘤/肝、肿瘤/肺、肿瘤/脾和肿瘤/骨骼肌放射性比值分别为5.31,1.88,1.57,3.58,4.16和5.92.（3）荷瘤鼠显像发现肿瘤部位明显浓聚99Tcm-RES,而201Tl、99Tcm-MIBI在肿瘤部位未见明显浓聚.（4）兔炎性反应和肿瘤模型显像示肿瘤部位放射性明显浓聚,而炎性反应部位放射性无明显浓聚,注药后6 h肿瘤/炎性反应部位放射性比值为3.12.结论 用放射性组合化学文库筛选出的小分子RES是一种与肿瘤高亲和力的多肽,有望成为一种肿瘤显像剂.     

99Tcm-RGD-4CK在动物体内的分布及显像

目的探讨^99Tc^m-环形精氨酸．甘氨酸-天冬氨酸九肽（RGD-4CK）在健康小鼠体内的生物分布及在健康家兔体内的动态显像表现。方法采用预锡化法以^99Tc^m直接标记RGD-4CK，3MM色谱纸层析测定^99Tc^m-RGD-4CK标记率，并计算其比活度。研究^99Tc^m-RGD-4CK于1、5、20、60、90、120、180和240min在健康小鼠体内的生物分布特性；通过SPECT显像，结合感兴趣区（ROI）时间-放射性曲线分析，观察240min内^99Tc^mmRGD-4CK在健康家兔体内的动态分布变化。结果^99Tc^mmRGD-4CK的标记率为（97．80±0．28）％，比活度为（11．91±0．04）TBq／mmol。小鼠血液放射性清除迅速，通过肾脏排泄较快，其余组织器官放射性均随时间逐渐降低，而脑放射性水平始终最低。家兔各组织器官放射性均随时间逐渐下降，与同一时间肾、心、肝相比，肺、胃、肌肉放射性呈低水平；1min双肾即显影，5min心、肝影开始减淡，肺放射性分布均匀，强度低于肝脏，膀胱显影；5min后膀胱影持续增浓，20min后软组织影逐渐减淡；胆囊始终未显影，腹部放射性呈持续低水平，胃区放射性始终缺损，颈部未见明显放射性浓聚。结论^99Tc^m-RGD-4CK制备方法简便，标记率高，体内稳定性好，具有比较珲椒并符合实际的动物体内动力学表现。     

99Tcm标记亲肿瘤三肽的实验研究

目的 进行99Tcm-精氨酸-谷氨酸-丝氨酸(RES)的亲肿瘤实验研究.方法 采用标准Fmoc固相合成法合成RES,在不同的试剂和温度(100 ℃或室温)条件下,以氯化亚锡为还原剂进行RES的99Tcm标记,优化标记条件.进行荷A549肺癌裸鼠99Tcm-RES显像并测定%ID/g,研究99TcmRES在荷瘤裸鼠体内的分布.比较兔炎性反应和肿瘤模型显像结果.结果 (1)酒石酸钠及氢氧化钠为缓冲剂,氯化亚锡为还原剂,100 ℃水浴10 min,RES放化纯最高达到85%;99Tcm-RES性能稳定,室温下放置6 h,放化纯仍达75%.(2)注射后0.5 h,99Tcm-RES多分布于心、肝、肾等血供丰富脏器,2 h血液的放射性(0.36%ID/g)降幅明显,仅相当于0.5 h(2.35%ID/g)的1/7;心、肝、肺的放射性降幅稍慢,但明显快于肿瘤;注射后0.5 h肿瘤放射性摄取为2.32%ID/g,6 h为1.54%ID/g,6 h后仍有超过60%的放射性滞留.99Tcm-RES注射后6 h肿瘤/血、肿瘤/心、肿瘤/肝、肿瘤/肺、肿瘤/脾和肿瘤/骨骼肌放射性比值分别为5.31,1.88,1.57,3.58,4.16和5.92.(3)荷瘤鼠显像发现肿瘤部位明显浓聚99Tcm-RES,而201Tl、99Tcm-MIBI在肿瘤部位未见明显浓聚.(4)兔炎性反应和肿瘤模型显像示肿瘤部位放射性明显浓聚,而炎性反应部位放射性无明显浓聚,注药后6 h肿瘤/炎性反应部位放射性比值为3.12.结论 用放射性组合化学文库筛选出的小分子RES是一种与肿瘤高亲和力的多肽,有望成为一种肿瘤显像剂.     

99Tcm-Ap4A显像探测动脉粥样硬化斑块的动物实验研究

目的探讨应用二磷酸腺苷(ADP)的类似物99Tcm-四磷酸二腺苷(Ap4A)显像探测动脉粥样硬化斑块的可行性.方法采用酒石酸亚锡还原99TcmO-4标记Ap4A,柱层析纯化,纸层析鉴定放射化学纯度.观察99Tcm-Ap4A在昆明小鼠体内的生物分布并测定动脉粥样硬化模型家兔病灶斑块/血液、病灶斑块/无斑块动脉壁的放射性比值,进行腹主动脉宏观放射自显影及正常家兔及动脉粥样硬化家兔体外体内显像.结果99Tcm-Ap4A的放射化学纯度为85%～91%.99Tcm-Ap4A在小鼠血液内清除迅速.注射99Tcm-Ap4A后30min粥样硬化组靶/血比值达3.17±1.27,靶/非靶比值为5.23±1.87.粥样硬化组自显影胶片上的曝光黑影与肉眼可见的动脉粥样硬化斑块有良好的一致性.体外显像正常家兔组腹主动脉未显影,粥样硬化组腹主动脉放射性浓聚清晰可见.体内显像粥样硬化组家兔的腹主动脉在注射99Tcm-Ap4A后15～30min与正常家兔组相比放射性浓聚明显增强,并持续到注药后3h.结论99Tcm-Ap4A是一种有潜力的可快速显示动脉粥样硬化斑块形成的显像剂.     

99Tcm-J591的制备及荷人前列腺癌裸鼠显像

目的 研究99Tcm-抗前列腺特异性膜抗原(PSMA)抗体J591与前列腺癌细胞体外结合性能、在荷人前列腺癌裸鼠显像及体内分布情况.方法 用改进的Schwarz方法进行99Tcm标记J591,经Sephadex G-50柱分离纯化;用纸层析法和三氯醋酸法测定标记率与放化纯;用流式细胞术测定99Tcm-J591与肿瘤细胞在体外的结合性能.以PSMA阳性的C4-2前列腺癌荷瘤裸鼠为实验组,PSMA阴性的PC3前列腺癌荷瘤裸鼠为对照组,2组均经静脉注射99Tcm-J591 6.2～ 8.5 MBq(25 μg/只)后,分别于2、6、12及24h后行γ显像,利用ROI技术获得各时间点T/NT(NT为对侧肌肉组织).12 h显像后分批处死裸鼠(实验组4只,对照组5只),取肿瘤、心、肝、肾、胃、骨骼、肌肉和血液等组织,测湿质量和放射性计数,计算％ID/g,采用两样本t检验比较2组间差异.结果 99Tcm直接标记J591的标记率为(78.9±6.2)％,放化纯为(92.3±5.1)％,放射性比活度为68.7 MBq/mg.流式细胞术分析结果显示,J591与99Tcm-J591在体外均能结合PSMA阳性的C4-2细胞,与PSMA阴性的PC3细胞不结合.实验组静脉注射99Tcm-J591后6h,肿瘤部位出现明显放射性浓聚,至12 h放射性浓聚范围增大,边缘更清晰,2、6、12和24 h T/NT分别为1.9±1.1、4.3±1.8、5.6±2.7和1.4±0.6;对照组肿瘤部位未见明显放射性浓聚,各时间点T/NT均小于2.体内分布结果显示:注药后12 h,实验组肿瘤放射性为(20.1±5.2) ％ID/g,对照组为(5.8±2.6)％ID/g,两者差异有统计学意义(t=5.37,P＜0.001);其余部位2组间放射性摄取差异无统计学意义(均t＜1.98,均P＞0.05).结论 99Tcm-J591具有良好的免疫活性和生物分布特性,对接种于裸鼠体内的人前列腺癌具有靶向定位性能,可望用于前列腺癌的导向诊断及导向治疗.     

99mTc标记抗心肌肌凝蛋白轻链单克隆抗体在体亲梗死心肌放射免疫显像研究

为探讨99mTc标记抗心肌肌凝蛋白轻链单克隆抗体(AMLCA)在体亲梗死心肌放射免疫显像的可行性,5只狗静脉注射99mTc-AMLCA后2、4、8、24h,对血液标本和各脏器进行放射性测量和γ像机显像.对2例心肌梗死狗进行在体99mTc-AMLCA心血池显像和99mTc-MIBI心肌灌注显像,并对其离体心脏进行γ显像和双感兴趣区双核素放射性测量.结果表明,注射后2、4、8、24h,血液99mTcAMLCA放射活性分别是(51.5±5.2)%、(27.3±3.1)%、(12.3±1.8)%和(5.6±0.6)%,心脏放射性分别是(11.2±1.2)%、(6.7±1.5)%、(5.5±0.9)%和(2.8±0.3)%,注射2h在体心脏γ显像最清晰,以后逐渐衰减,注射24h心脏不再显像.心梗狗在体99mTc-AML-CA心血池显像与99mTc-MIBI心肌灌注显像比较,前者放射浓聚区与后者放射缺损区吻合,其离体心脏γ显像放射性浓聚区TTC染色证实是梗死心肌,双感兴趣区双核素放射性测量表明,梗死心肌摄取99mTc-AMLCA具有特异性.本研究提示,99mTc-AMLCA在血中清除迅速且能被梗死心肌特异性摄取,在体99mTc-AMLCA心血池显像能显示梗死心肌,99mTc-AMLCA在体亲梗死心肌显像可行.     

99 Tcm-抗人粒细胞单克隆抗体对兔炎症的放射免疫显像

目的评价99Tcm-抗人粒细胞单克隆抗体(McAb) SZ-102在实验性炎症家兔放射免疫显像中的价值.方法以2-亚氨基噻吩盐酸盐(2-IT)修饰SZ-102,99Tcm-葡庚糖酸钠(GH)配体交换法标记SZ-102.兔左下肢炎症模型经耳缘静脉注入99Tcm-SZ-102,行SPECT显像,99Tcm标记非特异性鼠IgG作阴性对照.显像完毕处死动物,测定99Tcm-SZ-102离体炎症肌肉/血液和对侧正常肌肉/血液放射性比值.结果 99Tcm-SZ-102对家兔炎症部位显影清晰,其最佳显像时间为注射后2～4 h,而99Tcm标记非特异性鼠IgG对家兔炎症部位未能显影.血液半清除时间99Tcm-SZ-102 T1/2α为(0.10±0.04) h,T1/2β为(3.19±0.41) h.99Tcm-SZ-102显像离体炎症肌肉/血液和对侧正常肌肉/血液放射性比值分别为0.22±0.02和0.02±0.01.结论 99Tcm-SZ-102具有活体内炎症定位导向能力,显像时间短,对隐匿性炎症或肿瘤感染病灶的诊断有潜在的临床价值.     

New bone-seeking agent: Animal study of Tc-99m-incadronate

OBJECTIVE: Disodium cycloheptylaminomethylenediphosphonate monohydrate (incadronate disodium) is a third-generation bisphosphonate compound which potently inhibits bone resorption, and a highly effective drug in the treatment of metastatic bone disease. We first labeled incadronate disodium with 99mTc, and examined its biodistribution and bone uptake after intravenous injection in rats to assess its potential for clinical use as a bone-seeking agent for judgment of the therapeutic effect of incadronate on bone metastases. Bone scan with 99mTc-labeled incadronate (99mTc-incadronate) may yield important information prior to the use of incadronate for treatment of bone metastases. METHODS: Synthesis of 99mTc-incadronate was carried out by reduction of 99mTc-pertechnetate in the presence of SnCl2 and N2 gas. Normal rats were injected with 18.5 MBq (0.5 mCi) 99mTc-incadronate in a volume of 0.1 ml intravenously and then sacrificed at 15 min, 30 min, 1 h or 2 h (six rats at each time point) after injection. Samples of muscle, stomach, small intestine, kidney, liver and bone (femur) were taken and weighed. In addition, a 1-ml sample of blood was drawn from the heart, and urine was taken from the urinary bladder immediately after sacrifice. Samples were measured for radioactivity and expressed as percent uptake of injected dose per gram or per milliliter (% ID/g or ml). Bone-to-blood and bone-to-muscle uptake ratios were determined from the % ID/g or ml values for these organs. RESULTS: The greatest accumulation of 99mTc-incadronate was found in bone. Radioactivity in bone was as high as 3.22 +/- 0.68% ID/g at 2 hours after injection. Scintigraphic images of 99mTc-incadronate in normal rats revealed highly selective skeletal uptake. CONCLUSION: 99mTc-incadronate exhibited high uptake in bone, and relatively low uptake in soft tissue, suggesting that it may be useful as a bone-seeking agent for judgment of the therapeutic effect of incadronate on bone metastases, by determining the degree of its accumulation in metastatic bone lesions.     

新型骨显像剂99Tcm-BIPrDP的制备及生物学性质研究

目的 探讨99Tcm-1-羟基-3-(2-丁基-1H-咪唑-1-基)丙烷-1,1-双膦酸(BIPrDP)用于骨显像的可能性.方法 以2-丁基咪唑为原料,经过3步反应得到BIPrDP.以SnCl2为还原剂,在100℃下沸煮BIPrDP钠盐溶液(50 mg/ml,100μl)与新鲜淋洗的Na99TcmO4溶液(37.0 MBq)混合液30 min,制得99Tcm-BIPrDP.用TLC测定标记率和稳定性.测定99Tcm-BIPrDP在正辛醇-水中的脂水分配系数(log P)和在新鲜肝素抗凝的人血血浆中的血浆蛋白结合率.向ICR小鼠尾静脉注射0.2 ml (7.4 MBq) 99Tcm-BIP(r)DP,分别在5、10、15、30、60、120和240 min时处死小鼠,取其心、肝、脾、肺、肾、骨骼、肌肉、性腺、肠、胃、脑和血液,测其质量及放射性计数,计算％ ID/g及骨放射性与各组织中放射性的比值.计算血药清除动力学方程.对新西兰兔静脉注射99Tcm-BIPrDP后于不同时问显像.用单因素方差分析方法对不同时间各组织％ID/g进行统计学分析.结果 99Tcm-BIPrDP的标记率和放化纯均＞95％,在放置6h后仍具有很好的稳定性.99Tcm-BIPrDP在pH值为7.0和7.4时的log P分别为-2.396 ±0.035和-2.242±0.025,99Tcm-BIPrDP的血浆蛋白结合率为(47.07±0.05)％.在注射99Tcm-BIPrDP 30 min后小鼠骨摄取达到最大值(19.20％ID/g),且能持久,在4h时为18.98％ID/g.在所有的非靶向性组织中,99Tcm-BIPrDP在肾的摄取最高,5min时为24.50％ID/g,4h为5.22％ID/g.其他重要器官普遍摄取较低,在4h时肌肉和脑最低,分别为0.18 ％ID/g和0.03 ％ID/g.在5 min时99Tcm-BIPrDP在血液中的摄取为18.60％ID/g,随后迅速降低,在4h时仅为0.40％ID/g,血药动力学方程为C ＝9.109e-0.262t+2.696e-0.00558t.从药物清除曲线可看出该药在小鼠体内血液清除速率较快,与小鼠体内分布中的血液清除趋势一致.注射99Tcm-BIPrDP后1h即可获得清晰的兔骨显影,在其他软组织中摄取低,清除快.各组织不同时间％ ID/g差异有统计学意义(F=5.65 ～ 859.24,P均＜0.05).结论 99Tcm-BIPrDP制备方便,骨显影清晰,是一种较有潜力的新型骨显像剂.     

Rhenium-188 hydroxyethylidene diphosphonate: a new generator-produced radiotherapeutic drug of potential value for the treatment of bone metastases

The search for an ideal radioisotope for systemic radiotherapy continues. As a generator-produced radioisotope emitting both beta and gamma rays and having a short physical half-life of 16.9 h, rhenium-188 is a very good potential candidate for systemic radiotherapy. In this study, we labeled hydroxyethylidene diphosphonate (HEDP) with¹⁸⁸Re and analyzed the biodistribution and bone uptake following intravenous injection in rats to assess its potential for clinical use. The rats were injected with approximately 14.8 MBq (0.4 mCi)¹⁸⁸Re-HEDP in a volume of 0.1 ml intravenously and then sacrificed at 1 h, 24 h, or 48 h (four rats at each time). Samples (about 0.1 g) of lung, liver, kidney, spleen, testis, muscle, stool, and bone (thoracic vertebra) were taken and weighed carefully. In addition, a 1-ml sample of blood was drawn from the heart and 1 ml of urine was taken from the urinary bladder immediately after killing. Tissue concentrations were calculated and expressed as percent injected dose per gram or per milliliter (% ID/g or ml). Bone lesions were created in the right tibial bone in three rabbits to calculate the lesion to normal uptake ratio (UN ratio). The biodistribution data showed that the radioactivity in the bone tissue was as high as 1.877% ID/g at 1 h and that it climbed to 2.017% ID/g at 4 h. The activity level in the kidney was highest at 1 h but declined rapidly throughout the study. The radioactivities in the lung, liver, muscle, spleen, testis, blood, and stool were all lower than 0.3% ID/g at I h and also declined rapidly. The biological half-life in bone was the longest (60.86 h). In contrast, the biological half-lives in muscle and blood were short (2.99 h and 6.21 h respectively). The concentrations of radioactivity in muscle, spleen, testis, and stool were quite low throughout the study. Most of the radiotracer was excreted by the urinary system. The L/N ratio was 4.23±0.21 in rabbits injected with¹⁸⁸Re-HEDP and 4.25±0.23 in those injected with technetium-99m methylene diphosphonate. In conclusion, we would suggest that¹⁸⁸Re-HEDP is a very good potential candidate for the treatment of bone metastases because of the following characteristics: (1) it is generator produced; (2) it has a short half-life; (3) it emits gamma rays suitable for imaging; (4) there is highly selective uptake in the skeletal system and bone lesions; and (5) it has a low non-target uptake and rapid clearance in nonosseous tissue.     

Increased liver and spleen accumulation of Tc-99m methylene diphosphonate associated with intravenous injection of MRI contrast gadolinium-diethylenetriaminepentaacetic acid

Several conditions that can cause diffuse hepatic or splenic uptake of Tc-99m methylene diphosphonate (Tc-99m MDP) have been previously reported. Nevertheless, diffuse abnormal liver and spleen uptake of Tc-99m MDP associated with intravenous injection of magnetic resonance imaging contrast gadolinium-diethylenetriaminepentaacetic acid is not previously known. In our series, we reported diffuse increased Tc-99m MDP activity in the liver and spleen in bone scans in patients who received Tc-99m MDP injection shortly after contrast-enhanced magnetic resonance imaging.     

Altered Biodistribution of <Superscript>99m</Superscript>Tc-DPD on Bone Scan After Intravenous Iron Supplement

We report a case with altered biodistribution of ^99mTc-dicarboxypropane diphosphonate (^99mTc-DPD) on whole body bone scan after intravenous iron supplement therapy. A 47-year-old male patient who had recently been detected with a hepatic mass suggestive of hepatocellular carcinoma underwent bone scan as staging work-up before surgery. Bone scan images at 3 h after injection of ^99mTc-DPD demonstrated unusually increased blood pool activities in the heart, liver, and spleen with usual skeletal uptakes. The patient had been treated for severe anemia from hemorrhoid with two intravenous administration of ferric hydroxide carboxymaltose complex at approximately 22 h and 2 h prior to the ^99mTc-DPD injection, which we consider as the most probable cause of altered biodistribution of ^99mTc-DPD.     

Biodistribution on Tc-99m labeled somatostatin receptor-binding peptide (Depreotide,NeoTec) planar and SPECT studies

PURPOSE: To determine the biodistribution of Tc-99m labeled somatostatin receptor-binding peptide (Depreotide) on planar and SPECT studies of the thorax and upper abdomen in order to improve diagnostic accuracy. METHODS AND MATERIALS: Retrospectively 29 planar and SPECT studies from 28 patients (all males, average age of 65.79) were reviewed. All the patients had been referred for evaluation of solitary pulmonary nodules. Two to four hours after IV injection of 555- to 740-MBq (15-20 mCi) Tc-99m Depreotide, anterior and posterior total body images, and anterior, posterior, right lateral and left lateral planar images were obtained, and thoracic SPECT was acquired with a three-head gamma camera. The degree of uptake in the lungs, thoracic cage, and organs of the upper abdomen was rated from "0" to "++++". RESULTS: The range of normal activity in the thorax includes cardiac, "0"; pulmonary, "+"; rib, "+/++"; sternum, "++"; vertebrae, "++". The degree of normal activity seen in the upper abdominal organs includes liver and spleen, "+++", and kidneys, "+++/++++". Eight patients with emphysema had diffuse pulmonary uptake graded as "+/++". One patient with left pneumonectomy and radiation therapy to the left hemithorax had photon-deficiency in the left hemithorax and decreased to absent uptake including the vertebrae and ribs. Although some cases had background pulmonary uptake of Tc-99m Depreotide, the bone/ bone marrow activity of the thoracic cage including the ribs, sternum, and thoracic spine is sufficiently great enough to produce a clear distinction between bone and lung in the thoracic cavity that gives high-contrast resolution on SPECT. CONCLUSIONS: The intensity of radioactivity in the sub-diaphragmatic organs such as the liver, spleen, and kidneys provides useful guidance for the categorization of pulmonary lesions. The uptake of land marks such as the sternum, which is anteriorly located, and the thoracic vertebrae, which are posteriorly located in the thoracic cage, can be used in the localization of a Depreotide avid tumor.     

Comparison of 99Tcm complexes (NEP-DADT, ME-NEP-DADT and HMPAO) with 123IAMP for brain SPECT imaging in dogs

Several new lipophilic 99Tcm complexes have recently been described as alternatives to N-isopropyl (123I) iodoamphetamine (123IAMP) for measurement of regional cerebral blood flow (RCBF). In this study we have compared brain uptake and blood clearance of 99Tcm-N-ethylpiperidine-diamino dithiol (99Tcm-NEP DADT), its 4-methylated derivative (99Tcm-Me-NEP-DADT) and 99Tcm-hexamethyl-propylene-amine-oxime (99Tcm-HMPAO) with that of 123IAMP in two dogs. Single photon emission tomography (SPECT) was employed to measure brain accumulation and retention of the four radiopharmaceuticals. Cerebral uptake of the 99Tcm complexes (0.8-1.1%) was lower than that of 123IAMP (1.6% of the injected dose). There was considerable extracerebral activity in the dog's head, especially in the olfactory and snout regions. Because of slow blood clearance 99Tcm-HMPAO showed high uptake in these regions. Brain uptake of 99Tcm-HMPAO reached a plateau 5 to 10 min after intravenous injection and remained constant for the entire study period (1 h). 99Tcm-NEP-DADT, on the other hand, showed significant clearance from the brain after reaching maximal uptake at 10 to 15 min after injection. However, brain imaging with these agents was possible during the first 20 min. The mechanism of brain uptake, as well as the relationship between brain uptake and RCBF need to be evaluated for each of the four radiopharmaceuticals.     

Preclinical evaluation of isostructural Tc-99m- and Re-188-folate-Gly-Gly-Cys-Glu for folate receptor-positive tumor targeting

Objective

The purpose of the present study was to prepare isostructural Tc-99m- and Re-188-folate-Gly-Gly-Cys-Glu (folate-GGCE), and to evaluate the feasibility of their use for folate receptor (FR)-targeted molecular imaging and as theranostic agents in a mouse tumor model.

Methods

Folate-GGCE was synthesized using solid-phase peptide synthesis and radiolabeled with Tc-99m or Re-188. Radiochemical characterization was performed by radio-high-performance liquid chromatography. The biodistribution of Tc-99m-folate-GGCE was studied, with or without co-injection of excess free folate, in mice bearing both FR-positive (KB cell) and FR-negative (HT1080 cell) tumors. Biodistribution of Re-188-folate-GGCE was studied in mice bearing KB tumors. Serial planar scintigraphy was performed in the dual tumor mouse model after intravenous injection of Tc-99m-folate-GGCE. Serial micro-single photon emission computed tomography/computed tomography (SPECT/CT) studies were performed, with or without co-injection of excess free folate, in the mouse tumor model after injection of Tc-99m-folate-GGCE or Re-188-folate-GGCE.

Results

The radiolabeling efficiency and radiochemical stability of Tc-99m- and Re-188-folate-GGCE were more than 95 % for up to 4 h after radiolabeling. Uptake of Tc-99m-folate-GGCE at 1, 2, and 4 h after injection in KB tumor was 16.4, 23.2, and 17.6 % injected dose per gram (%ID/g), respectively. This uptake was suppressed by 97.4 % when excess free folate was co-administered. Tumor:normal organ ratios at 4 h for blood, liver, lung, muscle, and kidney were 54.3, 25.2, 38.3, 97.8, and 0.3, respectively. Tumor uptake of Re-188-folate-GGCE at 2, 4, 8, and 16 h after injection was 17.4, 21.7, 24.1, and 15.6 %ID/g, respectively. Tumor:normal organ ratios at 8 h for blood, liver, lung, muscle, and kidney were 126.8, 21.9, 54.8, 80.3, and 0.4, respectively. KB tumors were clearly visualized at a high intensity using serial scintigraphy and micro-SPECT/CT in mice injected with Tc-99m- or Re-188-folate-GGCE. The tumor uptake of these molecules was completely suppressed when excess free folate was co-administered.

Conclusion

Isostructural Tc-99m- and Re-188-folate-GGCE showed high and FR-specific uptake by tumors and generally favorable tumor:normal organ ratios. The tumor targeting capabilities of Tc-99m- and Re-188-folate-GGCE were clearly evident on serial imaging studies. This isostructural pair may have potential diagnostic and theranostic applications for FR-positive tumors.