深圳特区土壤和建筑材料中的放射性水平

应用200只天鼠研究了²⁴¹Am内污染时四种络合剂(Ca-DTPA, Zn-DTPA,嗤胺酸钠盐和H-73-IO)钓促排效果.实验目的是为²⁴¹Am内污染治疗确定首先促排药物及制定最佳促排方案.实验结果表明:在四种结合剂中Ca-DTPA和Zn-DTPA促排效果为最佳,能使骨²⁴¹Am含量降低到对照组的10%,肝²⁴¹Am含量降低到对照组的5%左右.喹胺酸钠盐在降低骨、肝²⁴¹Am含量方面也有效(统计上与DTPA无显著差别),但能导致肾脏²⁴¹Am蓄积,甚至略高于对照组.H-73-10虽有-些效果,但远不及DTPA.     

喹胺酸和LICAM(C)对大鼠体内238Pu和241Am的促排效果比较

喹胺酸(Quinamic acid, QAA, 811)是一种异哇啉类络合剂, 对钍有较好的促排效果。本文主要研究大鼠静脉注入(iv)²³⁸Pu和²⁴¹Am各26kBq/kg后1小时, 经皮下注入(so)不同剂量.(1～30μmol/kg)QAA, 或静脉注入核素后立即灌胃(po)QAA(30μmol/kg)对²³⁸Pu、²⁴¹Am的促排疗效, 并与LICAM(C)相比较。实验观察到QAA对降低骨肝中²³⁸Pu、²⁴¹Am的蓄积量有较好的作用, QAA对²³⁸Pu的促排效果高于对²⁴¹Am.在剂量(1～30μgmol/kg)对肝、肾中²³⁸Pu和骨、肾中²⁴¹Am蓄积量的降低, QAA优于LICAM(C)；灌胃QAA(30μttmol/kg)伍用NaHCO₃(5mmol/kg的)疗效, 对骨、肝中²³⁸Pu蓄积量的降低, QAA和LICAM(C)二间无差异(P>0.05), 但对²³⁸Pu在肾中蓄积量和对²⁴¹Am在骨, 肾中蓄积量的降低, QAA明显优于LICAM(C)。     

放射自显影术评价促排和阻吸收放射性核素的效果研究

放射性桉素对机体的作用特性及其损伤效应的呈现,是与该核素在体内的蓄积特性、转移和排除程度密功相关联的。因此,本文研究了不同放射自显影术对加速排除和阻止吸收放射性桉素的效果评价如下,(1)宏观放射自显影评价喹胺酸和DTPA对¹⁶⁹Yb的促排作用,(2)宏现放射自显影评价稳定性Yb于¹⁶⁹Yb在骨中的减少沉积作用}(8)微观放射自显影评价噎胺酸和DTPA对¹⁶⁹Yb促排作用的机理探讨。     

镅-铍中子源事故及其处理

1982年4月我国南方某地误拾²⁴¹Am-Be中子源,经多人传递后被钻开,致使人身、场所大面积受到a污染.本协作组对污染情况作了较全面的调查、测量和初步评价,对事故进行了相应的处理.经估算受照人员x外照射剂量最高.胸部0.12Sv,手部0.32Sv;Y的²⁴¹Am内污染量最高,约3.3×10³Bq.对Y等4名受照人员进行了促排治疗,显著地增加了尿和粪中²⁴¹Am的排出.事故后1.5年进行的医学检查,除淋巴细胞染色体畸变率增高外,无归因于辐射作用的医学所见.     

苯酚氨羧酸类螯合剂对放射性核素加速排除效果的研究

动物实验表明取代苯酚、苯二酚等氨羧酸螯合剂对放射性核素¹⁴⁴Ce,²³⁴Th都有较好的促排效果。这类螯合剂的促排效果与结构有密切关系。本文对合成的27个螯合剂的构效关系研究初步表明:邻苯二酚化合物优于对,间苯二酚化合物。邻、间、对苯二酚审一个羟基代之以其它基因的化合物如邻取代苯酚化合物其效果下降,对、间代苯酚化合物效果有所提高,但不及邻苯二酚类效果好。     

离子交换法处理60Co污染的γ辐照装置源井水

目的 选择合适的离子交换树脂处理⁶⁰Co污染的贮源井水,使污染的贮源井水中放射性水平低于10 Bq/L,满足排放要求。 方法 通过亚硝酸钴钾共沉淀-β计数法测量水样中⁶⁰Co的活度,比较两种不同离子交换树脂处理⁶⁰Co污染模拟井水的效果,并选择净化效果较好的离子交换树脂处理⁶⁰Co污染的源井水。 结果 MBD-15-SC型混合离子交换树脂对模拟井水中⁶⁰Co净化效果明显高于ZGCNR50型强酸性阳离子交换树脂,大约为5.8倍;采用多次两级MBD-15-SC型混合离子交换树脂循环处理污染的源井水,可使水中⁶⁰Co放射性浓度从4.16×10⁵ Bq/L降至1.16 Bq/L。 结论 采用多次两级MBD-15-SC型混合离子交换树脂可有效处理⁶⁰Co污染的源井水,处理后的贮源井水符合排放要求。     

五种络合剂对促排钍的疗效评价

本文对有较好排钍效果的811、8102、8307-7603和DTPA等五种络合剂, 从量效关系, 时效关系和疗效强度等方面进行比较。结果表明, 从尿粪中²³⁴Th的排出量的增加和组织中²³⁴Th蓄积量的降低为指标, 以8102的疗效为最佳, 其次是811, 但811使肾²³⁴Th菩积量有增加。DTPA和7603在高剂量时才有较好的排²³⁴Th效果, 且7603以粪²³⁴Th形式排出为主, 其疗效与DTPA、8307基本相当。     

云南芒市地区野生食用蘑菇中137Cs、40K含量及所致居民剂量估算

目的 检测可食用野生蘑菇中人工放射性核素¹³⁷Cs和天然放射性核素⁴⁰K的含量及分布特点,计算野生蘑菇中放射性核素水平及其所致剂量。方法 采集了产自云南省芒市的18类33份可食用野生蘑菇样品,用实验室低本底高纯锗（HPGe）γ谱仪分析了其中放射性核素¹³⁷Cs、⁴⁰K的含量。结果 33份样品中,仅1份样品¹³⁷Cs的含量在探测限之下,其余32份样品中均可检测出¹³⁷Cs,比活度范围值为0.45~339.58 Bq/kg（干重）,平均值25.47 Bq/kg（干重）。所有样品均检测出天然放射性核素⁴⁰K,核素比活度最小值和最大值分别为453.4、1 882.6 Bq/kg（干重）,平均值为815.1 Bq/kg（干重）。当去除只有1个样品数的蘑菇种类后,毛钉菇、美味牛肝菌、白牛肝菌、锈盖粉孢牛肝菌、香菇、茶褐牛肝菌6个种类蘑菇间¹³⁷Cs含量差异有统计学意义（F=21.13,P<0.05）,而⁴⁰K含量差异无统计学意义。结论 6类不同蘑菇中¹³⁷Cs含量不同,其中毛钉菇、香菇中人工放射性核素¹³⁷Cs含量相对较高。但食入此类蘑菇对成人所致待积有效剂量极其微小,不会影响健康。     

125I-UdR壳聚糖纳米微粒对肝癌细胞的内照射生物学效应

目的 评估¹²⁵I-UdR壳聚糖载药纳米微粒(¹²⁵I-UdR-CS-DLN)对肝癌细胞的内照射生物学效应.方法 采用激光共聚焦显微镜观察¹²⁵I-UdR-CS-DLN在肝癌细胞HepG2和人正常肝组织细胞HL-7702内的聚积和分布;通过MTT实验、流式细胞仪和单细胞凝胶电泳技术,评价内照射细胞生物学效应;采用TUNEL染色法观察兔肝原位肿瘤细胞经¹²⁵I-UdR-CS-DLN靶向治疗后的细胞凋亡.结果 纳米微粒作用30 min后,其在HepG2细胞质内的聚积大于HL-7702;当¹²⁵I-UdR-CS-DLN浓度大于37 kBq/ml时,HepG2细胞在纳米微粒作用后24、48 h的存活率显著低于HL-7702细胞(t=-4.46~6.31,P<0.05),且细胞周期G₁期阻滞明显, G₂/M期细胞明显受损;¹²⁵I-UdR-CS-DLN造成细胞DNA双链断裂的程度明显高于¹²⁵I-UdR,HepG2细胞的DNA损伤后修复能力显著低于HL-7702(Olive尾矩:t=2.94,P<0.05;彗尾DNA%:t=10.64,P<0.01);兔肝原位癌模型经介入被动靶向治疗后的TUNEL染色结果表明,¹²⁵I-UdR-CS-DLN可使兔肝原位肿瘤细胞产生明显的凋亡,而相同剂量¹²⁵I-UdR作用后肿瘤并未出现明显的凋亡.结论 ¹²⁵I-UdR-CS-DLN进入肝癌细胞的能力明显强于¹²⁵I-UdR,引起的DNA辐射损伤效应更强,可明显加剧肝癌细胞的凋亡,阻止DNA损伤修复.     

56Fe17+、12C6+重离子束与60Co γ射线对人淋巴细胞染色体畸变、细胞周期

目的 比较⁵⁶Fe¹⁷⁺、¹²C⁶⁺重离子束与⁶⁰Co γ射线对人淋巴细胞染色体畸变、周期、凋亡的影响。方法 ⁵⁶Fe¹⁷⁺、¹²C⁶⁺重离子束和⁶⁰Co γ射线分别照射人淋巴细胞系Peng-EBV,吸收剂量均为0、0.5和2.0 Gy,⁵⁶Fe¹⁷⁺重离子束剂量率为0.26～0.55 Gy/min,¹²C⁶⁺重离子束剂量率为0.30～0.50 Gy/min,γ射线照射剂量率为0.75 Gy/min。研究不同射线对染色体细胞畸变率、“双+环”畸变率的影响。利用流式细胞仪检测细胞周期和细胞凋亡。结果 ¹²C⁶⁺、⁵⁶Fe¹⁷⁺重离子与⁶⁰Co γ射线照射后细胞畸变率与0 Gy相比,差异有统计学意义（χ²=12.08～322.97,P<0.05）。“双+环”畸变率与0 Gy相比,差异有统计学意义（χ²=4.06～205.37,P<0.05）。其中,¹²C⁶⁺重离子束诱导的细胞畸变率和“双+环”畸变率最高,其次是⁵⁶Fe¹⁷⁺重离子束,而且二者均高于⁶⁰Co γ射线。⁵⁶Fe¹⁷⁺、¹²C⁶⁺离子束与⁶⁰Co γ射线均能诱导人淋巴细胞发生明显的G₂期阻滞,差异有统计学意义（t=-80.9～0.17,P<0.05）,¹²C⁶⁺重离子、γ射线及⁵⁶Fe¹⁷⁺重离子诱导的G₂期阻滞程度依次降低。⁵⁶Fe¹⁷⁺、¹²C⁶⁺离子束与⁶⁰Co γ射线均能促进细胞凋亡,差异有统计学意义（t=-22.65～0.87,P<0.05）,¹²C⁶⁺重离子、γ射线及⁵⁶Fe¹⁷⁺重离子诱导的早期凋亡率依次降低。结论 ⁵⁶Fe¹⁷⁺、¹²C⁶⁺离子束与⁶⁰Co γ射线均能诱导人淋巴细胞发生明显的染色体畸变、G₂期阻滞及细胞凋亡。¹²C⁶⁺离子束诱导的染色体畸变、周期阻滞和凋亡程度最高。⁵⁶Fe¹⁷⁺、¹²C⁶⁺离子束与γ射线的生物学效应与LET相关。     

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。     

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.     

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.     

Diagnostic Performance of 68Ga-DOTATATE PET/CT, 18F-FDG PET/CT and 131I-MIBG Scintigraphy in Mapping Metastatic Pheochromocytoma and Paraganglioma

Purpose

To evaluate the diagnostic performance of ⁶⁸Ga-DOTATATE ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) positron emission tomography (PET)/computed tomography (CT), ¹⁸F-FDG PET/CT and ¹³¹I-MIBG scintigraphy in the mapping of metastatic pheochromocytoma and paraganglioma.

Materials and Methods

Seventeen patients (male = 8, female = 9; age range, 13–68 years) with clinically proven or suspicious metastatic pheochromocytoma or paraganglioma were included in this prospective study. Twelve patients underwent all three modalities, whereas five patients underwent ⁶⁸Ga-DOTATATE and ¹³¹I-MIBG without ¹⁸F-FDG. A composite reference standard derived from anatomical and functional imaging findings, along with histopathological information, was used to validate the findings. Results were analysed on a per-patient and on per-lesion basis. Sensitivity and accuracy were assessed using McNemar’s test.

Results

On a per-patient basis, 14/17 patients were detected in ⁶⁸Ga-DOTATATE, 7/17 patients in ¹³¹I-MIBG, and 10/12 patients in ¹⁸F-FDG. The sensitivity and accuracy of ⁶⁸Ga-DOTATATE, ¹³¹I-MIBG and ¹⁸F-FDG were (93.3 %, 94.1 %), (46.7 %, 52.9 %) and (90.9 %, 91.7 %) respectively. On a per-lesion basis, an overall of 472 positive lesions were detected; of which 432/472 were identified by ⁶⁸Ga-DOTATATE, 74/472 by ¹³¹I-MIBG, and 154/300 (patient, n = 12) by ¹⁸F-FDG. The sensitivity and accuracy of ⁶⁸Ga-DOTATATE, ¹³¹I-MIBG and ¹⁸F-FDG were (91.5 %, 92.6 % p < 0.0001), (15.7 %, 26.0 % p < 0.0001) and (51.3 %, 57.8 % p < 0.0001) respectively. Discordant lesions were demonstrated on ⁶⁸Ga-DOTATATE, ¹³¹I-MIBG and ¹⁸F-FDG.

Conclusions

Ga-DOTATATE PET/CT shows high diagnostic accuracy than ¹³¹I-MIBG scintigraphy and ¹⁸F-FDG PET/ CT in mapping metastatic pheochromocytoma and paraganglioma.     

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.     

Placenta,embryo, and tumor uptake of 67Ga-citrate and 59Fe-citrate

The uptake of gallium citrate Ga⁶⁷ and ferrous citrate Fe⁵⁹ was studied in pregnant rats with or without a 4-dimethylamino-stilben (DS)-induced sarcoma tumor. The liver and placenta of the mother concentrated ⁶⁷Ga, while the uptake of ⁶⁷Ga in the embryo was minimal. However, the embryo showed higher concentrations of ⁵⁹Fe. Preloading with iron did not affect the ⁶⁷Ga uptake of the placenta, but increased the uptake in the blood and liver of the mother. With regard to ⁵⁹Fe uptake, iron loading only affected the embryo liver. Tumors and the placenta showed a similar ⁶⁷Ga uptake but a different incorporation of ⁵⁹Fe. The probable mechanisms involved are discussed.     

Molecular structures involved in 67Ga and 59Fe binding by placenta and tumors

The binding of ⁶⁷Ga and ⁵⁹Fe by placenta and tumors was compared. After sonification, about 50% of the total radioactivity was present in the insoluble fraction consisting of heavy subcellular particles (mitochondria, fragments of membranes, nuclei, etc.) and known to be rich in lipo- and glycoproteins. Heat denaturation and gel filtration were used to study transferrin and ferritin distribution in the supernatant. The differences between ⁵⁹Fe and ⁶⁷Ga uptake in this supernatant seemed to indicate that the transferrin-ferritin system plays a less important role in ⁶⁷Ga binding than in ⁵⁹Fe binding.     

Value of 111In-DOTA-lanreotide and 111In-DOTA-DPhe1-Tyr3-octreotide in differentiated thyroid cancer: results of in vitro binding studies and in vivo comparison with 18F-FDG PET

Purpose Radioiodine-negative thyroid cancer presents diagnostic and therapeutic difficulties, warranting the implementation of new imaging and treatment strategies. The purpose of this study was twofold. First, we investigated in vitro the binding characteristics of ¹¹¹In-DOTA-lanreotide (¹¹¹In-DOTA-LAN) and ¹¹¹In-DOTA-DPhe¹-Tyr³-octreotide (¹¹¹In-DOTA-TOC) to cells derived from differentiated thyroid cancer (DTC). Second, we evaluated the value of somatostatin receptor (SSTR) scintigraphy with these radioligands, as compared with ¹⁸F-fluorodeoxyglucose (FDG) positron emission tomography (PET), for the detection of tumour lesions in DTC patients.Methods Binding of ¹¹¹In-DOTA-LAN and ¹¹¹In-DOTA-TOC to cells isolated from surgically removed thyroid tissue was evaluated in vitro by performing saturation and displacement studies. Eighteen DTC patients with elevated thyroglobulin (12 radioiodine-negative, six radioiodine-positive) were investigated with ¹¹¹In-DOTA-LAN, ¹¹¹In-DOTA-TOC and ¹⁸F-FDG PET scans.Results Large numbers of SSTR binding sites for ¹¹¹In-DOTA-LAN and ¹¹¹In-DOTA-TOC were found on the cells investigated. Both SSTR radioligands exhibited a high binding affinity for these SSTR binding sites. ¹¹¹In-DOTA-LAN and ¹¹¹In-DOTA-TOC scintigraphy detected 37 and 33 lesions, respectively, in 17 (94%) patients each, whereas ¹⁸F-FDG PET revealed 30 lesions in 15 (83%) patients. Uptake of both SSTR radioligands was found in several radioiodine-negative sites. No striking differences in lesion imaging by ¹¹¹In-DOTA-LAN and ¹¹¹In-DOTA-TOC were found. In both radioiodine-negative and radioiodine-positive patients, more lesions were SSTR-positive/¹⁸F-FDG-negative than were ¹⁸F-FDG-positive/SSTR-negative.Conclusion Adding a SSTR scan with these radioligands to the diagnostic work-up increases the diagnostic capacity in DTC, and should be considered particularly in radioiodine-negative patients with elevated thyroglobulin levels.These studies were supported in part by the Austrian National Bank (Anniversary Foundation, Projects No. 7487 and 8185) and by a Foundation of the Mayor of the City of Vienna.     

Intraindividual comparison of <Superscript>68</Superscript>Ga-DOTA-TATE and <Superscript>18</Superscript>F-DOPA PET in patients with well-differentiated metastatic neuroendocrine tumours

Aim  To compare the diagnostic impact of ⁶⁸Ga-DOTA-TATE and ¹⁸F-DOPA PET in the diagnosis of well-differentiated metastatic neuroendocrine tumours (NET). Methods  PET/CT using both ⁶⁸Ga-DOTA-TATE and ¹⁸F-DOPA was performed in 25 patients with histologically proven metastatic NET (nine gut, five pancreas, six lung, one paranasal sinus, four with unknown primary). Analyses of PET examinations were patient-based (pathological uptake: yes/no), and based on tumour regions (primary tumour if present and metastases of liver, lung, bones and lymph nodes). The results were compared with the results of contrast enhanced CT, and with plasma serotonin levels, which were available in 24 of the 25 patients. Results  Patient-based sensitivities were 96% for ⁶⁸Ga-DOTA-TATE PET and 56% for ¹⁸F-DOPA PET. ⁶⁸Ga-DOTA-TATE PET delineated metastases in 54 of 55 positive metastatic tumour regions in contrast to 29 of 55 delineated by ¹⁸F-DOPA PET. Overall, ⁶⁸Ga-DOTA-TATE was superior to ¹⁸F-DOPA in 13 patients (two patients showed fewer positive tumour regions with ¹⁸F-DOPA PET). The results were comparable in 12 patients. In 13 of 24 patients, plasma serotonin levels were elevated, and 11 of these 13 patients showed pathological uptake of ¹⁸F-DOPA. Of the 11 patients with normal levels of serotonin, 3 also showed positive ¹⁸F-DOPA uptake. In patients positive for ¹⁸F-DOPA uptake the maximum tumour SUVs were correlated with the levels of serotonin (r=0.66, p=0.01). Conclusion  In this study ⁶⁸Ga-DOTA-TATE PET proved clearly superior to ¹⁸F-DOPA PET for detection and staging of NET. ¹⁸F-DOPA uptake tended to be increased in those patients with elevated plasma serotonin. We conclude that ¹⁸F-DOPA PET should be employed in patients with NET with negative ⁶⁸Ga-DOTA-TATE PET and elevated plasma serotonin.     

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.