Iodine-125 labeled phenylphosphonic acid: A new radiopharmaceutical for long-term investigations of the skeleton

A skeletal seeking radiopharmaceutical labeled with a long-lived radionuclide was developed to evaluate regional bone formation and its subsequent resorption. The agent is [phosphonate (phenylmethylene hydroxy) bis]-I-125 or I-125 PA. Tissue distribution studies in mice (N=16) showed approximately 40% of the administered dose to be retained by the skeleton up to 336 hours post IV injection. The percentage of the dose accumulated by the thyroid gland remained at less than 0.5%, indicating minimal deiodination of the I-125 PA. Whole body retention studies in the same species revealed a triexponential release pattern with the longest component comprising 33% of the dose with a biologic half-life of 962 days. A fractured rat tibia model was studied with I-125 PA and Tc-99^m MDP. Chronic loss of the I-125 PA relative to normal tibia was quantitated: five days (62.8%); 30 days (47.4%). Concomitant increased uptake of the Tc-99^m MDP was observed at the fracture site relative to normal: five days (186%); 30 days (1,041%). The above data suggest that I-125 PA can be utilized to measure acute bone formation and chronic resorption.     

回旋加速器放射性药物生产场所的防护设计与分析

【摘要】目的掌握回旋加速器放射性药物生产场所的辐射危害因素及其水平,为场所的防护设计和放射性药物生产的放射防护提供指导。方法以某医院引进的1台HM-20S型回旋加速器及其药物生产场所为研究对象,依据国家有关法规和技术标准确定场所中的辐射危害因素类别及场所级别,对相应的防护设施与措施进行分析和评价。结果制订出放射性药物生产场所的辐射防护设计方案,其中对热室工作区出人口采取GMP（良好作业规范）设计;估算出了控制区外围和场所关注点的辐射水平,在60mmPb厚壁工作箱内进行222GBq的18F操作时,操作位置的剂量率为9．6ixSv／h;明确了回旋加速器机房内活化产物的来源及其防护措施;带有自屏蔽的回旋加速器运行时,机房内的0,浓度远低于标准规定的职业接触限值。结论该放射性药物生产场所的防护设计充分考虑了放射性污染和外照射的防护,但其防护方案中还需对回旋加速器机房及防护门的屏蔽设计进行优化。     

Training and Education Requirements for Authorized Users of Therapeutic Radiopharmaceuticals: Changes Under Consideration for 10CFR35.390 and Their Potential Impact

The US Nuclear Regulatory Commission (NRC) and 38 Agreement States have the regulatory authority to promulgate and enforce regulations related to the use of radioisotopes for medical purposes. Elements of these regulations include training and experience (T&E) requirements for individuals authorized to use the agents. These regulations are specified in 10CFR35.390. At this time, the NRC is considering significant revisions to the T&E requirements. This article describes current regulations and concerns related to the proposed changes and details the ACR organizational response.     

Lymphoseek: A Molecular Radiopharmaceutical for Sentinel Node Detection

Background: Lymphoseek is a new radiopharmaceutical that accumulates in lymphatic tissue by binding to a receptor that resides on the surface of macrophage cells. We conducted a phase I clinical trial in which Lymphoseek was compared with filtered [^99mTc]sulfur colloid (fTcSC) for sentinel node detection in patients with breast cancer.Methods: Twelve women (42–71 years) with breast cancer were randomly assigned to a 3-hour imaging protocol with peritumoral/subdermal injections (.5 mCi) of either Lymphoseek (1 nmol; molecular weight, 28 kDa; diameter, .007 m) or .2 m of fTcSC. Serial images were acquired for 180 minutes. Sentinel nodes, excised within 4.2 to 7.3 hours of administration, were assayed in a dose calibrator.Results: The receptor-binding agent, Lymphoseek, exhibited a significantly (P = .0025) faster injection site clearance (rate, .255 ± .147/hour; fTcSC rate, .014 ± .018/hour); the mean Lymphoseek clearance half-time was 2.72 ± 1.57 hours compared with 49.5 ± 38.5 hours for fTcSC. The primary sentinel node uptake of Lymphoseek (range, .02%–1.12%; mean, .55% ± .43%) and fTcSC (range, .00%–1.93%; mean, .65% ± .63%) did not differ (P = .75). Lymphoseek exhibited a lower mean number of sentinel nodes per study (n = 1.3) than fTcSC (n = 1.7) and a higher concordance with Lymphazurin.Conclusions: The molecular receptor-binding agent Lymphoseek demonstrated faster injection site clearance and equivalent primary sentinel node uptake when compared with fTcSC.     

Radiopharmaceutical model using99mTc-MIBI to evaluate amifostine protection against doxorubicin cardiotoxicity in rats

The aim of our study was to use an in vivo radiopharmaceutical model to investigate the cytoprotective effect of amifostine against doxorubicin-induced cardiotoxicity. Male Wistar rats were randomly divided into four groups (n = 6): 1) Saline (control); 2) Doxorubicin (DOX; 10 mg/ kg(-l) intraperitoneally); 3) Amifostine (AMI; 200 mg/kg(-1) intraperitoneally); 4) Doxorubicin plus amifostine (DOX + AMI). Amifostine was injected 30 minutes before doxorubicin in Group 4. 99mTc-MIBI, 20 MBq/0.2 ml(-1), was injected through the tail vein 72 hours after the drug administration. Rats were killed and samples of myocardium were removed by dissection 60 minutes after the injection of radiopharmaceutical. Radioactivity in each organ sample was counted using a Cd(Te) detector equipped with RAD 501 single-channel analyzer. The percent radioactivity was expressed as a percentage of the injected dose per gram of tissue (%ID/g(-1)). The %ID/g(-1) activity was calculated by dividing the activity in each sample by the total activity injected and mass of each organ. 99mTc-MIBI uptake as %ID/g(-1) was 1.194 +/- 0.502 and 0.980 +/- 0.199 in the control and AMI groups, respectively. Doxorubicin administration resulted in a significant increase in %ID/ g(-1) (3.285 +/- 0.839) (p < 0.05). Amifostine administration 30 minutes before doxorubicin injection resulted a significant decrease in %ID/g(-1) (2.160 +/- 0.791) (p < 0.05) compared with doxorubicin alone. The results showed that amifostine significantly attenuated doxorubicin-induced cardiotoxicity.     

In vivo assessment of cardiac insulin resistance by nuclear probes using an iodinated tracer of glucose transport

Purpose Insulin resistance, implying depressed cellular sensitivity to insulin, is a risk factor for type 2 diabetes and cardiovascular disease. This study is the first step towards the development of a technique of insulin resistance measurement in humans with a new tracer of glucose transport, [¹²³I]6-deoxy-6-iodo-D-glucose (6DIG). Methods We investigated 6DIG kinetics in anaesthetised control rats and in three models of insulin-resistant rats: fructose fed, Zucker and ZDF. The study of myocardial 6DIG activity was performed under two conditions: first, 6DIG was injected under the baseline condition and then it was injected after a bolus injection of insulin. After each injection, radioactivity was measured over 45 min by external detection via NaI probes, in the heart and blood. A tri-compartment model was developed to obtain fractional transfer coefficients of 6DIG from the blood to the heart. Results These coefficients were significantly increased with insulin in control rats and did not change significantly in insulin-resistant rats. The ratio of the coefficient obtained under insulin to that obtained under basal conditions gave an index of cardiac insulin resistance for each animal. The mean values of these ratios were significantly lower in insulin-resistant than in control rats: 1.16 ± 0.06 vs 2.28 ± 0.18 (p < 0.001) for the fructose-fed group, 0.92 ± 0.05 vs 1.62 ± 0.25 (p < 0.01) for the Zucker group and 1.34 ± 0.06 vs 2.01 ± 0.26 (p < 0.05) for the ZDF group. Conclusion These results show that 6DIG could be a useful tracer to image cardiac insulin resistance.     

Production, quality control and pharmacokinetic studies of Ho-EDTMP for therapeutic applications

¹⁶⁶Ho-EDTMP is a major therapeutic agent which is widely used in bone palliation therapy. In this study, a ¹⁶⁶Ho-EDTMP complex was prepared successfully using an in-house synthesized EDTMP ligand and ¹⁶⁶HoCl₃. Ho-166 chloride was obtained by thermal neutron irradiation (1 × 10¹³ ncm⁻²s⁻¹) of natural Ho(NO₃)₃ samples (specific activity = 3–5 GBq/mg), dissolved in acidic media. The radiochemical purity of ¹⁶⁶Ho-EDTMP was checked by ITLC (>99%) and stability studies in presence of human serum and final preparation were performed. The biodistribution of ¹⁶⁶Ho-EDTMP and ¹⁶⁶HoCl₃ in wild-type rats was checked by scarification. SPECT imaging of ¹⁶⁶Ho-EDTMP was also performed in wild-type rats. A comparative accumulation study for ¹⁶⁶Ho-EDTMP and ¹⁶⁶HoCl₃ was performed for vital organs up to 48h. Significant bone accumulation (>70%) of the tracer in 48h was observed.     

放射性药品生产单位雾化固定高浓度131I放射性气溶胶的初步研究

目的 验证雾化固定技术用于控制高浓度¹³¹I气溶胶的可行性。方法 对国内某放射性药品生产单位操作¹³¹I的手套箱内高浓度¹³¹I气溶胶实施雾化固定。测量箱式内¹³¹I气溶胶浓度,进行结果分析。结果 手套箱内（289 ±9） DAC和（304 ±6） DAC的¹³¹I气溶胶,固定处理120 min后,气溶胶浓度分别降至（21.7 ±2.0） DAC和（26.2 ±1.8） DAC;手套箱内（259 ±10） DAC的¹³¹I气溶胶,固定处理180 min后,气溶胶降至（1.80 ±0.18） DAC;固定完成24 h后检测结果表明,没有发生气溶胶再悬浮。结论 雾化固定技术可以在较短时间内有效控制有限空间内¹³¹I气溶胶浓度,降低工作人员内照射风险,可用于放射性药品生产单位作为处理高浓度¹³¹I气溶胶的应急管理办法。