Oral Zn-DTPA Therapy for Reducing 141Ce Retention in Suckling Rats

Summary

In neonatal rats DTPA reduced the intestinal retention of cerium ingested as an additive in its chloride form to milk. It also reduced retention of absorbed cerium. A similar decrease of cerium retention in gut and whole body was obtained after simultaneous or 24 hours' delayed DTPA administration.     

The placental transfer of cerium: experimental studies and estimates of doses to the human fetus from 141Ce and 144Ce

PURPOSE: To measure the transfer of cerium from mother to fetus in experimental animals and estimate doses to the human fetus following intakes of radioisotopes of Ce. MATERIALS AND METHODS: Cerium-141 in chloride solution was administered intravenously to rats at different stages of pregnancy (days 9.5, 12.5 or 18.5), and retention in the embryo/fetus and associated tissues was measured 3 days later in each case. Retention in rat fetal tissues on day 21.5 (shortly before birth) was also measured after administration of 141Ce chloride 1 month prior to conception or 141Ce citrate on day 18.5. Cerium-141 chloride was administered to guinea pigs on day 50 for measurements of fetal retention on day 57 (shortly before birth). RESULTS: Retention of 141Ce in the rat embryo/fetus, measured at 3 days after administration to the mother, increased from about 0.00002% of injected activity per embryo/fetus on day 12.5 to about 0.014% on day 21.5 of gestation. However, the relative concentrations of 141Ce in the embryo/fetus and mother (CF:CM ratio) were between 0.005 and 0.01 in each case. After 141Ce administration prior to conception, retention by the rat fetus on day 21.5 was substantially lower than after short-term administration. Comparison of retention of 141Ce on day 21.5 after administration on day 18.5 as either chloride or citrate showed similar levels in maternal tissues but greater transfer to the fetus (CF:CM ratio of 0.03). Retention in the guinea pig fetus in late gestation at 7 days after administration of (141)Ce chloride was about 0.05% injected activity per fetus, corresponding to a CF:CM ratio of about 0.02. CONCLUSION: These results and other published animal data have been used to specify CF:CM ratios for use in the calculation of doses to the human fetus. The values used were 0.05 for intakes during pregnancy and 0.01 for intakes prior to conception. Doses to the offspring after maternal ingestion of 141Ce or 144Ce are largely due to irradiation from activity in the maternal colon and are insensitive to CF:CM. After inhalation, however, absorption of Ce to blood is much greater and doses to the offspring are dominated by the contribution from activity in the fetus, and therefore dependent on the CF:CM ratio used.     

The Effect of Dietary Phosphorus on the Metabolism of Calcium and Strontium in the Rat

Summary

An investigation has been made of the way in which changes in dietary phosphorus within the physiological range influence the comparative metabolism of calcium and strontium in the rat. Radioactive calcium and strontium were used as tracers.

The absorption of both calcium and strontium after oral administration was dependent on the phosphorus level in the diet, but not to the same degree. The skeletal ratio ⁸⁵Sr/⁴⁷Ca decreased by some 40 per cent as the dietary phosphorus was increased from 0·5 to 1·3 g per cent.

After intraperitoneal injection of radioactive calcium and strontium, the skeletal retention of ⁸⁵Sr was about 25 per cent more on a diet containing 1·3 per cent phosphorus than on a diet containing 0·5 per cent phosphorus. Skeletal retention of calcium varied little.

It is concluded that renal discrimination against strontium as well as intestinal absorption of calcium and strontium were affected by the phosphorus content of the diet, but in opposite directions.     

3H-TdR与125I-UdR掺入淋巴细胞增殖的比较

目的 比较 ³H-TdR与 ¹²⁵I-UdR掺入淋巴细胞的增殖效应。方法 用 ³H-TdR与 ¹²⁵I-UdR掺入法测定淋巴细胞和Daudi淋巴瘤细胞的增殖效应。结果 ³H-TdR和 ¹²⁵I-UdR在正常淋巴细胞中的掺入率分别为20.95%±1.06%和1.00%±0.04%,在Daudi淋巴瘤细胞中的掺入率分别为29.94%±4.10%和6.02%±0.73%。 ³H-TdR在细胞中的掺入率明显高于 ¹²⁵I-UdR;且 ³H-TdR和 ¹²⁵I-UdR在淋巴瘤细胞中的掺入率高于正常淋巴细胞。结论 就淋巴细胞而言,作为示踪剂 ¹²⁵I-UdR不能替代 ³H-TdR;但对于淋巴瘤细胞,能否代替 ³H-TdR有待于进一步研究。     

Treatment of Radioresistant Cancers–Proceedings of the International Symposium on the Prospects for Treatment of Radioresistant Cancers Held in Kyto (Japan), May 21st 1979

Summary

Using autoradiographic methods it was noted that S phase cells at the bottom of the crypts in the small intestine were the most efficient scavengers of exogenous injected thymidine. The efficiency of the incorporation of ³H-TdR (salvage pathway of DNA synthesis) by cells at the crypt base (stem cell zone) was twice as high as for the S phase cells at the top of the crypt (maturing proliferative cells). There were no such position-dependent differences in incorporation of ³H-UdR (de novo pathway of DNA synthesis). Radiation (0·75–5·0 Gy ¹³⁷Cs γ-rays) inhibited the incorporation of ³H-TdR very rapidly and this was also cell-position dependent. The cells at the bottom of the crypt were the most affected. The injection of cold thymidine before ³H-TdR changed the pattern of the incorporation of ³H-TdR along the side of the crypt in a very similar way to radiation, and the grain number was decreased predominantly in the cells at lower positions.

The possibility of the existence of a regional gradient of endogenous thymidine (reutilization from intestinal sources), and the influence of irradiation on the gradient of thymidine incorporation resulting from direct and abscopal effects of whole body exposure, are discussed.     

In vivo monitoring of intranuclear p27 protein expression in breast cancer cells during trastuzumab (Herceptin) therapy

IntroductionTrastuzumab, a humanized antibody directed against the Her2 receptor, induces the expression of p27^kip1, an intranuclear cyclin-dependent kinase inhibitor in some breast cancer cells. The aim of this study was to develop a radioimmunoconjugate (RIC) to monitor trastuzumab-induced p27^kip1 protein up-regulation in vivo.Materials and MethodsAnti-p27^kip1 IgG was purified, and conjugated to diethylenetriaminopentaacetate, to allow radiolabeling with ¹¹¹In for in vivo detection. Then tat peptide (GRKKRRQRRRPPQGYG), containing a nuclear localization sequence (underlined), was conjugated to the Fc-domain of IgG, using NaIO₄ oxidation of carbohydrates and the resulting Schiff base stabilized with NaCNBH₃. The conjugate was radiolabeled with ¹¹¹In, yielding [¹¹¹In]-anti-p27^kip1-tat. ¹¹¹In labeling efficiency, purity and p27^kip1 binding were measured. Trastuzumab-induced p27^kip1 up-regulation was assessed in a panel of breast cancer cell lines by Western blot analysis. Uptake and retention of [¹¹¹In]-anti-p27^kip1-tat were measured in MDA-MB-361 and SKBr3 cells after exposure to trastuzumab. Uptake of [¹¹¹In]-anti-p27^kip1-tat was determined at 72 h postintravenous injection in MDA-MB-361 xenografts in athymic mice treated with trastuzumab or saline.Results[¹¹¹In]-anti-p27^kip1-tat was synthesized to 97% purity. The RIC was able to bind to p27^kip1 protein and internalized in the cells and was transported to the nuclei of MDA-MB-361 cells. The level of p27^kip1 protein in MDA-MB-361 cells was increased after exposure to clinically relevant doses of trastuzumab for 3 days. Trastuzumab-mediated induction of p27^kip1 was not associated with increased cellular uptake or nuclear localization of [¹¹¹In]-anti-p27^kip1-tat (6.53±0.61% vs. 6.98±1.36% internalized into trastuzumab-treated vs. control cells, respectively). However, retention of [¹¹¹In]-anti-p27^kip1-tat at 72 h was increased approximately twofold (13.5±1.3% vs. 6.6±0.6% of internalized [¹¹¹In]-anti-p27^kip1-tat was retained in trastuzumab-treated vs. control cells, respectively; P=.016). Immunohistochemistry showed up-regulation of p27^kip1 in trastuzumab-treated xenografts. Tumour uptake of [¹¹¹In]-anti-p27^kip1-tat was significantly higher in trastuzumab-treated compared to control animals (6.5±0.9 vs. 4.8±0.1 %ID/g at 72 h postinjection, respectively; P=.0065).Conclusion[¹¹¹In]-Anti-p27^kip1-tat may be useful for monitoring changes in the expression of the intranuclear protein, p27^kip1. Up-regulation of p27^kip1 resulted in increased retention of [¹¹¹In]-anti-p27^kip1-tat in cells treated with trastuzumab. Modest, but statistically significantly higher, retention was also observed in tumours in mice treated with trastuzumab. Since responsiveness to trastuzumab correlated to up-regulation of p27^kip1, it may be possible to use [¹¹¹In]-anti-p27^kip1-tat to guide treatment with Herceptin and other drugs which alter p27^kip1 expression.     

HER-2受体放射性配体99Tcm-TP1623的制备及其在正常动物体内的分布

目的 探讨HER-2受体放射性配体 ⁹⁹Tc^m-B2-S22-AFA(⁹⁹Tc^m-TP1623)在健康小鼠体内的生物分布和健康家兔体内的动态显像分布.方法 采用氯化亚锡间接法 ⁹⁹Tc^m标记TP1623,3MM色谱纸层析测定 ⁹⁹Tc^m-TP1623标记率,计算其比活度;通过体外稳定性实验、血清蛋白结合实验和油/水分配实验,鉴定标记产品理化性质;研究 ⁹⁹Tc^m-TP1623于1、5、10、30、60和120 min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 ⁹⁹Tc^m-TP1623在健康家兔体内的动态分布变化.结果 ⁹⁹Tc^m-TP1623标记率为(96.4±0.1)%,比活度为(24.35±0.06)TBq/mmol,室温下放置6 h后放化纯度为(95.03±0.97)%.油/水分配系数P为－(2.51±0.15).小鼠血液放射性清除快,通过肾脏排泄较快,心、肺、肝、肌肉、骨骼等放射性随时间延长逐渐减低,60 min后放射性呈明显低水平,肠道放射性则随时间缓慢增加.脑放射性始终呈最低水平.健康家兔体内 ⁹⁹Tc^m-TP1623血池影消退迅速,主要通过肾脏排泄,见胆囊、肠道排泄影,胃区和颈部未见放射性浓聚,脑组织始终呈低本底.结论 ⁹⁹Tc^m-TP1623制备方法简便,标记率及产品比活度高,体内、外稳定性好,具有优良的动物体内动力学特性.     

应对福岛核事故我国食品和饮用水的放射性监测

目的 汇总分析日本福岛核电站事故发生后我国沿海城市和主要内陆城市食品和饮用水放射性的抽样监测结果,评价是否对我国居民的健康造成影响.方法 根据国家标准方法,制定应对日本福岛核事故对我国食品和饮用水的监测方案,统一数据报送格式,对数据进行对比分析.结果 4月2日北京露天生长菠菜样品中,监测到极微量的人工放射性核素131I,此后在全国范围内10种露天生长的蔬菜中也检测出131I,最高值为菠菜样品3.1 Bq/kg,到5月初未再检测出.牛奶、海产品和饮用水样品中未检测到人工放射性核素.结论 监测到的蔬菜中131I来自日本福岛核电站事故释放,与此次事故期间欧洲一些国家食品中的的131I水平相一致,远低于1986年切尔诺贝利核电站事故时我国蔬菜中131I活度,其对公众所致吸收剂量极其微小,不会对我国境内公众造成影响.     

18F-FLT和18F-FDG评价食管癌细胞照射后超早期生物学反应

目的 比较18F-氟代脱氧胸腺嘧啶(18F-FLT)和18F-氟代脱氧葡萄糖(18F-FDG)在反映食管癌细胞受照后超早期生物学反应的差异.方法 将人食管癌Eca-109细胞分别接受5、10、15 Gy剂量X射线照射,照射后2、4、8h检测细胞对18F-FDG和18F-FLT摄取率的变化,以及细胞相对存活率和ATP表达情况的变化.结果 5 Gy照射后2、4h,细胞对18F-FDG摄取率与对照组相比分别减少了9.45％和16.4％,差异无统计学意义;但15 Gy照后2h,对18F-FDG摄取率却增加了26.5％(=3.04,P＜0.05),其余照射组对18F-FDG摄取率均有明显减少(F=25.75,P＜0.05).5 Gy照后2h,18F-FLT摄取率(3.65±0.41)％与对照组(4.00±0.42)％相比,差异无统计学意义,其余照射组对18F-FLT摄取率与对照组比较均有明显减少(F=33.93,P＜0.05).在5、10、15 Gy照后2、4、8h,各组细胞相对存活率差异无统计学意义.经不同剂量照射后,细胞对18F-FLT摄取率与ATP浓度之间的相关性(r=0.887,P＜0.05)优于18F-FDG与ATP浓度之间的相关性(r=0.622,P＞0.05).结论 18F-FDG和18 F-FLT两者均可反映食管癌细胞照射后超早期生物学反应,18F-FLT比18F-FDG能较好地反映食管癌细胞照射后超早期生物学反应.     

Synthesis and application of molecular probe for detection of hydroxyl radicals produced by Na125I and gamma-rays in aqueous solution

Purpose: To synthesize N-(3-(3-aminopropylamino)propyl)-2-oxo-2H-chromene-3-carboxamide (7), a novel DNA-binding, coumarin-based, fluorescent hydroxylradical (^?OH) indicator and to assess its quantum efficiency compared with that of coumarin-3-carboxylic acid (1) and N1,N12-bis[2-oxo-2H-chromene-3-carbonyl]- 1,12-diamine-4,9-diazadodecane (9).

Materials and methods: Using computer-generated molecular modeling, 7 and 9 and their respective 7-hydroxylated derivatives 8 and 10 were docked onto DNA dodecamer d(CGCGAATTCGCG)2, the ligand–DNA complexes were energy minimized, and binding free energies and inhibition constants were calculated. Compound 7 was judged an appropriate target molecule and was synthesized. Compounds 1, 7, and 9 were incubated with Na¹²⁵I or irradiated with ¹³⁷Cs γ-rays, and the influence of pH, dose, type of radiation, and the concentration of indicator on fluorescence yield were determined.

Results: Non-fluorescent 7 and 9 are converted to fluorescent, 7-hydroxylated derivatives 8 and 10 after interaction with ^?OH in aqueous solution. For 1, 7, and 9, hydroxylation yield increases linearly with both Na¹²⁵I dose (0–700×10⁶ decays) and ¹³⁷Cs dose (0–11.0 Gy). Fluorescence induction is significantly reduced at acidic pH and the fluorescent quantum yield of 8 is ～3 times that of 2 or 10 at pH 7.0. With Na¹²⁵I incubation and γ-ray irradiation, the fluorescence signal of 7 increases linearly with concentration and saturates at ～50 μM.

Conclusion: Compound 7 quantifies lower concentrations of ^?OH than do 1 and 9. This detector is therefore likely to be a good reporter of ^?OH produced within a few nanometers of DNA.     

Preparation and preliminary bioevaluation of 99mTc(CO)3-11β-progesterone derivative prepared via click chemistry route

IntroductionProgesterone receptors (PRs) overexpressed in breast cancers serve as potential targets for developing radiotracers for use in nuclear medicine. Hence, suitably derivatized progesterone can be envisaged as a potential vector for targeting overexpression of receptors in breast cancer. In the present article, we report the preparation of a ^99mTc(CO)₃-progesterone triazole using the Cu(I)-catalyzed novel click chemistry route. Preliminary evaluation of the radiolabeled derivative has been carried out in binding studies with MCF 7 cell lines.Methods11-Hydroxyprogesterone has been synthetically derivatized to 11-azidoprogesterone. Subsequently, the cycloaddition reaction between progesterone azide and propargyl glycine was carried out to prepare 1,4-bifunctionalized progesterone triazole analogue. The clicked progesterone triazole derivative was radiolabeled with ^99mTc and characterized by HPLC. The chemical characterization of ^99mTc(CO)₃-progesterone triazole has been carried out by preparing its corresponding rhenium complex using the [NEt₄]₂[Re(CO)₃Br₃] precursor. While in vitro studies were carried out in MCF7 cell lines, in vivo distribution studies were performed in female Swiss mice.ResultsThe radiolabeled complex could be prepared in >95% radiochemical yield as determined by HPLC. In vitro studies of ^99mTc(CO)₃-progesterone complex in MCF7 cell lines overexpressing receptors for breast cancer showed binding up to 30%. In vivo distribution studies in female Swiss mice have shown uterine uptake of 0.41 (0.06) % ID/g at 3 h postinjection (pi) and retention therein till 24 h pi.ConclusionThe present study demonstrates a novel and facile route for preparation of ^99mTc-labeled progesterone complex using click chemistry. This strategy can be further extended towards preparation of radiolabeled complexes of other steroidal derivatives.     

2017—2020年北京地区大气气溶胶中7 Be和210 Pb放射性活度浓度监测与分析

目的 监测与分析2017—2020年北京地区大气气溶胶中⁷Be和²¹⁰Pb放射性活度浓度变化情况,为有效防治空气污染提供科学依据。方法 利用大流量空气气溶胶采样器（SnowWhite）采集气溶胶样品1 074份,其中春季、夏季、秋季和冬季分别采集275、266、262和271份。使用低本底高纯锗伽马谱仪（ORTEC）分析气溶胶样品中⁷Be和²¹⁰Pb放射性活度浓度。结果 2017—2020年北京地区大气气溶胶中⁷Be放射性活度浓度的变化范围为0.56~14.84 mBq/m³,平均值为6.84 mBq/m³。²¹⁰Pb放射性活度浓度的变化范围为0.01~9.37 mBq/m³,平均值为3.19 mBq/m³。2017—2020年北京大气气溶胶⁷Be和²¹⁰Pb放射性活度浓度在春、夏、秋、冬四季中差异均有统计学意义（F=32.66、93.93,P<0.05）,其中⁷Be放射性活度浓度春季最高,秋季次之,夏季和冬季最低,²¹⁰Pb放射性活度浓度由高到低分别为冬季、秋季、春季、夏季。结论 2017—2020年北京地区大气气溶胶中⁷Be和²¹⁰Pb放射性活度浓度处于正常涨落水平范围内。     

miR-141过表达增强人食管癌细胞的放射敏感性

目的 研究miR-141对食管癌细胞放射敏感性的影响及可能的作用机制。方法 将miR-141 mimic或miR-对照转染到食管癌KYSE-150细胞中,分别使用qRT-PCR和Western blot技术检测miR-141和增殖相关蛋白Ki67、凋亡相关蛋白Bax和Bcl-2的表达。CCK-8,流式细胞术及克隆形成实验检测放射处理后细胞的放射敏感性变化。结果 随放射剂量的增加,食管癌细胞中miR-141表达逐渐降低（t=2.57~8.96,P<0.05）。miR-141过表达抑制了细胞的增殖和克隆形成能力,促进了KYSE-150细胞凋亡,使得放射敏感性增高（t=3.24,P<0.05）。此外,与对照组相比,miR-141过表达显著抑制KYSE-150细胞中的Ki67和Bcl-2蛋白表达（t=6.56、8.24,P<0.01）,并促进Bax蛋白表达（t=3.24,P<0.01）,进一步证实了miR-141增强食管癌细胞的放射敏感性。结论 miR-141通过调控细胞增殖和凋亡相关蛋白表达增强食管癌细胞的放射敏感性。     

Synthesis and in vivo studies of a specific monoamine oxidase B inhibitor: 5-[4-(benzyloxy)phenyl]-3-(2-cyanoethyl)-1,3,4-oxadiazol-[11C]-2(3H)-one

We report the radiochemical synthesis of a specific MAO B inhibitor, namely 5-[4-(benzyloxy)phenyl]-3-(2-cyanoethyl)-1,3,4-oxadiazol-[¹¹C]-2(3H)-one (2b) (in vitro IC₅₀=4nM and selectivity over 71000 for MAO B), by cyclization of its hydrazide precursor1 with [¹¹C]phosgene. The reaction occurred within 2 min. The product obtained after HPLC purification,2b, had a high specific activity (11.1–22.2 GBq/µmol), allowing its use in experiments as a radiotracer in vivo. Biodistribution of2b in the CNS and in the peripheral organs of the rat, and positron emission tomography (PET) studies in the living baboon brain, pretreated or not withl-deprenyl (1 mg/kg, 1 h), an irreversible MAO B-specific inhibitor, were undertaken. The results showed a good uptake of2b in all organs of the rat, with a rapid clearance from the blood (10 min). Metabolite analyses in plasma and in the diencephalon of the rat showed that2b was the only radioactive compound in brain structure whereas in plasma three other radioactive products appeared. PET experiments show that in thel-deprenyl-pretreated baboon brain, specific binding of2b represents around 70% of total radioactivity, whereas in the blood and plasma the radioactivity cleared rapidly (15 min).     

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。     

Identification and regional distribution in rat brain of radiometabolites of the dopamine transporter PET radioligand [<Superscript>11</Superscript>C]PE2I

Purpose We aimed to determine the composition of radioactivity in rat brain after intravenous administration of the dopamine transporter radioligand, [¹¹C]PE2I. Methods PET time-activity curves (TACs) and regional brain distribution ex vivo were measured using no-carrier-added [¹¹C]PE2I. Carrier-added [¹¹C]PE2I was administered to identify metabolites with high-performance liquid radiochromatography (RC) or RC with mass spectrometry (LC-MS and MS-MS). The stability of [¹¹C]PE2I was assessed in rat brain homogenates. Results After peak brain uptake of no-carrier-added [¹¹C]PE2I, there was differential washout rate from striata and cerebellum. Thirty minutes after injection, [¹¹C]PE2I represented 10.9 ± 2.9% of the radioactivity in plasma, 67.1 ± 11.0% in cerebellum, and 92.5 ± 3.2% in striata, and was accompanied by two less lipophilic radiometabolites. [¹¹C]PE2I was stable in rat brain homogenate for at least 1 h at 37°C. LC-MS identified hydroxylated PE2I (1) (m/z 442) and carboxyl-desmethyl-PE2I (2) (m/z 456) in brain. MS-MS of 1 gave an m/z 442→424 transition due to H₂O elimination, so verifying the presence of a benzyl alcohol group. Metabolite 2 was the benzoic acid derivative. Ratios of ex vivo measurements of [¹¹C]PE2I, [¹¹C]1, and [¹¹C]2 in striata to their cognates in cerebellum were 6.1 ± 3.4, 3.7 ± 2.2 and 1.33 ± 0.38, respectively, showing binding selectivity of metabolite [¹¹C]1 to striata. Conclusion Radiometabolites [¹¹C]1 and [¹¹C]2 were characterized as the 4-hydroxymethyl and 4-carboxyl analogs of [¹¹C]PE2I, respectively. The presence of the pharmacologically active [¹¹C]1 and the inactive [¹¹C]2 is a serious impediment to successful biomathematical analysis.     

Chronic exposure by ingestion of environmentally relevant doses of 226Ra leads to transient growth perturbations in fathead minnow (Pimephales promelas,Rafinesque, 1820)

Abstract

Purpose: To assess the impact of environmentally relevant levels of ingested ²²⁶Ra on a common freshwater fish species.

Methods: Fathead minnow (Pimephales promelas, Rafinesque) were obtained at the first feeding stage and established on a commercial fish food diet containing ²²⁶Ra in the activity range 10 mBq/g^?1, –10,000 mBq/g^?1. They remained on this diet for 24 months and were sampled invasively at 1,6,18 and 24 months to assess growth, biochemical indices and accumulated dose and non-invasively also at 12 and 15 months to assess growth.

Results: Fish fed 10 and 100 mBq/g^?1 diet showed a small transitory deregulation of growth at 6 and 12 months. Fish fed higher activities showed less significant or insignificant effects. There was a trend at 18 months which was stronger at 24 months for the population distribution to change in all of the ²²⁶Ra fed groups so that smaller fish were smaller and bigger fish were bigger than the controls. There were also significant differences in the ratios of protein:DNA at 24 months which were seen as a trend but were not significant at earlier time points.

Conclusions: Fish fed a radium diet for 2 years show a small and transitory growth dysregulation at 6 and 12 months. The effects predominate at the lower activities suggesting hormetic or homeostatic adjustments. There was no effect on growth of exposure to the high activities ²²⁶Ra. This suggests that radium does not have a serious impact on the ecology of the system and the level of radium that would be transferred to humans is very low. The results may be important in the assessment of long-term environmental impacts of ²²⁶Ra exposure.     

Quantitation of cardiac sympathetic innervation in rabbits using 11C-hydroxyephedrine PET: relation to 123I-MIBG uptake

Purpose Although ¹¹C-hydroxyephedrine (¹¹C-HED) PET is used to map cardiac sympathetic innervation, no studies have shown the feasibility of quantitation of ¹¹C-HED PET in small- to medium-sized animals. Furthermore, its relation to ¹²³I-MIBG uptake, the most widely used sympathetic nervous tracer, is unknown. The aims of this study were to establish in vivo sympathetic nerve imaging in rabbits using ¹¹C-HED PET, and to compare the retention of ¹¹C-HED with that of ¹²³I-MIBG.Methods Twelve rabbits were assigned to three groups; control (n=4), chemical denervation by 6-hydroxydopamine (6-OHDA) (n=4) and reserpine treated to inhibit vesicular uptake (n=4). After simultaneous injection of ¹¹C-HED and ¹²³I-MIBG, all animals underwent dynamic ¹¹C-HED PET for 40 min with arterial blood sampling. The ¹¹C-HED retention fraction and normalised ¹¹C-HED activity measured by tissue sampling were compared with those measured by PET.Results Both the ¹¹C-HED retention fraction and the normalised ¹¹C-HED activity measured by PET correlated closely with those measured by tissue sampling (R=0.96027, p<0.001 and R=0.97282, p<0.001, respectively). Inhibition study by 6-OHDA resulted in a significant reduction in retention (90%) for both ¹¹C-HED and ¹²³I-MIBG. Reserpine pretreatment reduced ¹¹C-HED retention by 50%, but did not reduce ¹²³I-MIBG retention at 40 min after injection.Conclusion Non-invasive quantitation of cardiac sympathetic innervation using ¹¹C-HED PET is feasible and gives reliable estimates of cardiac sympathetic innervation in rabbits. Additionally, although both ¹¹C-HED and ¹²³I-MIBG are specific for sympathetic neurons, ¹¹C-HED may be more specific for intravesicular uptake than ¹²³I-MIBG in some situations, such as that seen in reserpine pretreatment.     

Radiosensitivity of C. Parvum-stimulated Spleen to Acute 60Co and Low Dose Rate 137Cs and 252Cf Irradiation

Summary

Stimulation of spleen growth by injection of C. parvum led to rapid organ enlargement, and acute ⁶⁰Co or low dose rate (LDR) ¹³⁷Cs or ²⁵²Cf irradiation reduced the maximum enlargement achieved. Irradiations were carried out 3 days after CP injection. Sigmoid dose–response curves were observed for the fraction of maximum enlargement achieved after acute ⁶⁰Co. After low dose rate ¹³⁷Cs or ²⁵²Cf irradiation, exponential dose-response curves of very different slope were observed. Acute and LDR γ-radiation produced reduced effects in the stimulated and proliferating spleen compared to LDR ²⁵²Cf neutron/γ-irradiation which had relative biological effectiveness = 4·0 versus low dose rate ¹³⁷Cs.     

[<Superscript>18</Superscript>F]EF3 is not superior to [<Superscript>18</Superscript>F]FMISO for PET-based hypoxia evaluation as measured in a rat rhabdomyosarcoma tumour model

Purpose  The aim of this investigation was to quantitatively compare the novel positron emission tomography (PET) hypoxia marker 2-(2-nitroimidazol-1-yl)-N-(3[¹⁸F],3,3-trifluoropropyl)acetamide ([¹⁸F]EF3) with the reference hypoxia tracer [¹⁸F]fluoromisonidazole ([¹⁸F]FMISO). Methods  [¹⁸F]EF3 or [¹⁸F]FMISO was injected every 2 days into two separate groups of rats bearing syngeneic rhabdomyosarcoma tumours. In vivo PET analysis was done by drawing regions of interest on the images of selected tissues. The resulting activity data were quantified by the percentage of injected radioactivity per gram tissue (%ID/g) and tumour to blood (T/B) ratio. The spatial distribution of radioactivity was defined by autoradiography on frozen tumour sections. Results  The blood clearance of [¹⁸F]EF3 was faster than that of [¹⁸F]FMISO. The clearance of both tracers was slower in tumour tissue compared with other tissues. This results in increasing T/B ratios as a function of time post tracer injection (p.i.). The maximal [¹⁸F]EF3 tumour uptake, compared to the maximum [¹⁸F]FMISO uptake, was significantly lower at 2 h p.i. but reached similar levels at 4 h p.i. The tumour uptake for both tracers was independent of the tumour volume for all investigated time points. Both tracers showed heterogeneous intra-tumoural distribution. Conclusions  [¹⁸F]EF3 tumour uptake reached similar levels at 4 h p.i. compared with tumour retention observed after injection of [¹⁸F]FMISO at 2 h p.i. Although [¹⁸F]EF3 is a promising non-invasive tracer, it is not superior over [¹⁸F]FMISO for the visualisation of tumour hypoxia. No significant differences between [¹⁸F]EF3 and [¹⁸F]FMISO were observed with regard to the intra-tumoural distribution and the extra-tumoural tissue retention.