Optimisation study of α-cyclotron production of At-211/Po-211g for high-LET metabolic radiotherapy purposes

The production of no-carrier-added (NCA) α-emitter ²¹¹At/^211gPo radionuclides for high-LET targeted radiotherapy and immunoradiotherapy, through the ²⁰⁹Bi(α,2n) reaction, together with the required wet radiochemistry and radioanalytical quality controls carried out at LASA is described, through dedicated irradiation experiments at the MC-40 cyclotron of JRC-Ispra. The amount of both the γ-emitter ²¹⁰At and its long half-lived α-emitting daughter ²¹⁰Po is optimised and minimised by appropriate choice of energy and energy loss of α particle beam. The measured excitation functions for production of the main radioisotopic impurity ²¹⁰At→²¹⁰Po are compared with theoretical predictions from model calculations performed at ENEA.     

A simple and rapid technique for radiochemical separation of iodine radionuclides from irradiated tellurium using an activated charcoal column

A simple and inexpensive method for the separation of medically useful no-carrier-added (nca) iodine radionuclides from bulk amounts of irradiated tellurium dioxide (TeO₂) target was developed. The β⁻ emitting ¹³¹I radionuclide, produced by the decay of ¹³¹Te through the ^natTe(n, γ)¹³¹Te nuclear reaction, was used for standardization of the radiochemical separation procedure. The radiochemical separation was performed by precipitation followed by column (activated charcoal) chromatography. Quantitative post-irradiation recovery of the TeO₂ target material (98–99%), in a form suitable for reuse in future irradiations, was achieved. The overall radiochemical yield for the complete separation of ¹³¹I was 75–85% (n=8). The separated nca ¹³¹I was of high, 99%, radionuclidic and radiochemical purities and did not contain detectable amounts of the target material. This method can be adopted for the radiochemical separation of other different iodine radionuclides produced from tellurium matrices through cyclotron as well as reactor irradiation.     

A comprehensive evaluation of charged-particle data for production of the therapeutic radionuclide Pd

¹⁰³Pd is an important radionuclide having a half-life of 16.99 d, which is suitable for internal radiation therapy, especially used for the treatment of prostate cancer. Its production in no-carrier-added form is done via charged-particle-induced reactions and the data are available in EXFOR library. We evaluated six charged-particle-induced reactions, namely ^natAg(p,x)¹⁰³Pd, ¹⁰³Rh(p,n)¹⁰³Pd, ¹⁰³Rh(d,2n)¹⁰³Pd, ¹⁰⁰Ru(α,n)¹⁰³Pd, ¹⁰¹Ru(α,2n)¹⁰³Pd, and ¹⁰²Ru(³He,2n)¹⁰³Pd process. In the first case, analysis was done up to about 100 MeV but in other cases only up to about 25 or 40 MeV. Furthermore, an evaluation of the data for the ^natAg(p,x)¹⁰³Ag process was also done since it may serve as a typical example for the ¹⁰³Ag→¹⁰³Pd precursor system. A statistical procedure supported by nuclear model calculations using the codes STAPRE, EMPIRE 2.19, and TALYS was used to validate and fit the experimental data. The recommended sets of data derived together with confidence limits are reported. The application of those data, particularly in the calculation of integral yields, is discussed. A comparison of the investigated routes from the viewpoint of practical applicability to the production of ¹⁰³Pd is given. Presently the ¹⁰³Rh(p,n)¹⁰³Pd reaction is the method of choice.     

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.     

An experimental study on the antitumor effect of 131I-17-AAG in vitro and in vivo

Objective  To observe the antitumor effect of ¹³¹I-17-allylamino-17-demethoxygeldanamycin (¹³¹I-17-AAG) in vitro/in vivo and explore its antitumor mechanism with a view to its potential therapeutic application. Methods   ¹³¹I-17-AAG was prepared by the reaction of 17-AAG with Na [¹³¹I] in the presence of hydrogen peroxide. The effects of ¹³¹17-AAG on cell growth inhibition and cell cycle distribution in vitro were studied in BEL-7402 cells lines. Following BEL-7402 tumor implantation by subcutaneous xenografts into nude mice, the reagents were injected through the tail vein, and the tumor volume was measured and analyzed. At the end of the experiment, tumor specimens were processed for histopathological analysis. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) was used to investigate apoptosis. The expression change of Akt2 was tested by Western-blot analysis. Results  Methyl-thiazolyl-tetrazolium assay showed inhibition rates of 27.7 ± 5.3%, 57.3 ± 4.3%, and 63.7 ± 3.1%, in Na¹³¹I group, 17-AAG group, and ¹³¹I-17-AAG group, respectively. The inhibition rate in the ¹³¹I-17-AAG group differed significantly between N^a131I group and 17-AAG group (F = 229.49, P < 0.001). Following 48 h of treatment with the drug in each group, flow cytometry analysis indicated that detected sub-G peaks (black) were 1.54 ± 0.13%, 5.72 ± 1.05%, 12.97 ± 1.44%, and 20.65 ± 1.36%, in dimethyl sulfoxide (DMSO) group, Na¹³¹I group, 17-AAG group, and ¹³¹I-17-AAG group, respectively. Following infusion for 32 days, the tumor volumes in the ¹³¹I-17-AAG group were significantly smaller than those in the DMSO group (F = 24.18, P < 0.001) or the ¹³¹I group (F = 20.68, P < 0.001). Histopathological and TUNEL analyses showed that ¹³¹I-17-AAG inhibited the proliferation of tumor cells and induced apoptosis. The expression of Akt2 in ¹³¹I-17-AAG was significantly lower than that in the DMSO group or ¹³¹I group. Conclusions   ¹³¹I-17-AAG can effectively inhibit the growth of BEL-7402 tumor cells in vitro and in vivo. ¹³¹I-17-AAG is a promising agent for the treatment of BEL-7402 cell tumor.     

New measurements and evaluation of excitation functions for (p,xn), (p,pxn) and (p,2pxn) reactions on 133Cs up to 70 MeV proton energy

Cross sections for production of the therapeutic radioisotope ¹³¹Cs via the ¹³³Cs(p,3n)¹³¹Ba→¹³¹Cs route were investigated at cyclotrons. Excitation functions of the ¹³³Cs(p,x)^{133m,133mg,131mg,129g,129m,128}Ba, ^{132,129cum,127cum}Cs and ^{129m(ind),127cum,125cum}Xe nuclear reactions were measured up to 70 MeV proton energy. The experimental data were compared to the results of model calculations performed by means of ALICE-IPPE, EMPIRE-II and TALYS computer codes. Good overall agreement was observed. On the basis of the measured excitation functions integral yields were deduced. Charged particle production routes of ¹³¹Cs are discussed.     

Repeated injections of 131I-rituximab show patient-specific stable biodistribution and tissue kinetics

Purpose It is generally assumed that the biodistribution and pharmacokinetics of radiolabelled antibodies remain similar between dosimetric and therapeutic injections in radioimmunotherapy. However, circulation half-lives of unlabelled rituximab have been reported to increase progressively after the weekly injections of standard therapy doses. The aim of this study was to evaluate the evolution of the pharmacokinetics of repeated ¹³¹I-rituximab injections during treatment with unlabelled rituximab in patients with non-Hodgkins lymphoma (NHL).Methods Patients received standard weekly therapy with rituximab (375 mg/m²) for 4 weeks and a fifth injection at 7 or 8 weeks. Each patient had three additional injections of 185 MBq ¹³¹I-rituximab in either treatment weeks 1, 3 and 7 (two patients) or weeks 2, 4 and 8 (two patients). The 12 radiolabelled antibody injections were followed by three whole-body (WB) scintigraphic studies during 1 week and blood sampling on the same occasions. Additional WB scans were performed after 2 and 4 weeks post ¹³¹I-rituximab injection prior to the second and third injections, respectively.Results A single exponential radioactivity decrease for WB, liver, spleen, kidneys and heart was observed. Biodistribution and half-lives were patient specific, and without significant change after the second or third injection compared with the first one. Blood T_1/2, calculated from the sequential blood samples and fitted to a bi-exponential curve, was similar to the T_1/2 of heart and liver but shorter than that of WB and kidneys. Effective radiation dose calculated from attenuation-corrected WB scans and blood using Mirdose3.1 was 0.53+0.05 mSv/MBq (range 0.48–0.59 mSv/MBq). Radiation dose was highest for spleen and kidneys, followed by heart and liver.Conclusion These results show that the biodistribution and tissue kinetics of ¹³¹I-rituximab, while specific to each patient, remained constant during unlabelled antibody therapy. RIT radiation doses can therefore be reliably extrapolated from a preceding dosimetry study.     

Renal excretion of iodine-131 labelledmeta-iodobenzylguanidine and metabolites after therapeutic doses in patients suffering from different neural crest-derived tumours

Iodine-131 labelledmeta-iodobenzylguanidine ([¹³¹I]MIBG) is used for diagnostic scintigraphy and radionuclide therapy of neural crest-derived tumours. After administration of therapeutic doses of [¹³¹I]MIBG (3.1–7.5 GBq) to 17 patients (n=32 courses), aged 2–73 years, 56%±10%, 73%±11%, 80%±10% and 83%±10% of the dose was cumulatively excreted as total radioactivity in urine att=24 h, 48 h, 72 h and 96 h, respectively. Except for two adult patients, who showed excretion of 14%–18% of [¹³¹I]meta-iodohippuric acid ([¹³¹I]MIHA), the cumulatively excreted radioactivity consisted of >85% [¹³¹I]MIBG, with 6% of the dose excreted as free [¹³¹I]iodide, 4% as [¹³¹I]MINA and 2.5% as an unknown iodine-131 labelled metabolite. Cumulative renal excretion rates of total radioactivity and of [¹³¹I]MIBG appeared to be higher in neuroblastoma and phaeochromocytoma patients than in carcinoid patients. Based on the excretion of small amounts of [¹³¹I]meta-iodobenzoic acid in two patients, a possible metabolic pathway for [¹³¹I]MIBG is suggested. The degree of metabolism was not related to the extent of liver uptake of radioactivity.     

Systemic Endoradiotherapy with Carrier-Added 4-[131I]Iodo-L-Phenylalanine: Clinical Proof-of-Principle in Refractory Glioma

Purpose

To explore feasibility, tolerability, dosimetry and probable efficacy of intravenous endoradiotherapy with carrier-added 4-[¹³¹I]iodo-L-phenylalanine (c.a. ¹³¹I-IPA) in refractory high-grade glioma.

Methods

Two male patients (45 and 50 years), with long-standing, extensively pre-treated gliomas and evidence of progression underwent single intravenous injections of 2 and 4 GBq of c.a. ¹³¹I-IPA, respectively. Tumour targeting was verified by ¹³¹I-IPA single-photon emission computed tomography (SPECT). Metabolic and morphological changes indicative of tumour response were assessed by sequential [¹⁸F]fluoroethyltyrosine (¹⁸F-FET) positron emission tomography (PET) and contrast-enhanced magnetic resonance imaging (MRI) following therapy. Further monitoring included clinical state, safety laboratory, quality of life and dosimetry. Absorbed mean organ and whole-body doses were determined according to the Medical Internal Radiation Dose (MIRD) scheme using OLINDAEXM based on serial planar scintigraphy.

Results

Both patients tolerated the treatment well. No evidence of acute or delayed organ toxicity was observed. ¹³¹I-IPA accumulated in the tumour recurrences identified by MRI/¹⁸F-FET. In patient 1, PET showed progressively decreasing maximum standardised uptake values (SUV_max) over 10 months, indicating metabolic response, paralleled by reduced contrast enhancement and tumour volume on MRI. Progression occurred 18 months after therapy. Treatment was repeated using 6.6 GBq of ¹³¹I-IPA, to which no response was observed. Patient 2, followed-up for 3 months after therapy, showed stable disease on MRI and PET. Mean absorbed whole body doses ranged from 0.13 to 0.17 mSv/MBq, with the highest absorbed organ doses to kidneys, bladder and heart (0.86-1.23; 0.49-0.6 and 0.45-0.56 mSv/MBq).

Conclusion

Systemic endoradiotherapy using up to 6.6 GBq of c.a.¹³¹I-IPA is not associated with clinically detectable toxicity. Measurable anti-tumour effects in gliomas were observed. ¹³¹I-IPA warrants further evaluation as glioma therapy.     

No evidence of chromosome damage in children and adolescents with differentiated thyroid carcinoma after receiving 131I radiometabolic therapy, as evaluated by micronucleus assay and microarray analysis

Purpose  As ¹³¹I therapy, used to achieve ablation of thyroid gland remnant, can cause chromosome damage in cultured peripheral lymphocytes especially, we investigated whether administration of radioiodine may induce early genome damage in peripheral T lymphocytes of adolescents with differentiated thyroid carcinoma (DTC). Methods  We studied 11 patients, aged 14.8 ± 3.1 years, who assumed ¹³¹I (range: 1.11–4.44 GBq) to ablate thyroid remnant. A blood sample for micronucleus assay and for evaluating expression of some genes involved in the DNA repair or the apoptosis pathways was obtained from each patient 1 h before (T₀) and 24 (T₁) and 48 h (T₂) post-radioiodine administration. Results  Compared to T₀, we did not find any difference in the number of micronucleated cells at both T₁ and T₂ in any subject. Nine out of 11 patients had altered expression levels in a majority of the DNA repair and apoptosis genes at T₁, which decreased at T₂. Conclusions  We demonstrated for the first time that peripheral cells of DTC children and adolescents who received ¹³¹I at a mean dosage of 3.50 ± 0.37 GBq did not show chromosome damage within 48 h from the end of radiometabolic therapy. This may be due to a prompt activation of the cell machinery that maintains the integrity of the genome to prevent harmful double-strand breaks from progressing to chromosome mutations, either by repairing the lesions or by eliminating the most seriously damaged cells via apoptosis. Statement on financial support. The present study did not receive any extramural financial assistance. It was supported exclusively by the Azienda Ospedaliero-Universitaria Pisana.     

131I标记纳米脂质体靶向治疗结肠癌的实验研究

目的 研究¹³¹I-antiEGFR-BSA-PCL对LS180细胞结肠癌裸鼠移植瘤内照射的治疗效果。方法 构建抗表皮生长因子受体(EGFR)标记的纳米脂质体及EGFR靶向性。通过荧光共聚焦显微镜、细胞摄碘实验观察纳米载体的靶向性及LS180细胞对其摄取情况。将裸鼠40只按随机数字表法分为4组,通过瘤体内注射的方式向移植瘤内分别注射74 MBq (740 MBq/ml) ¹³¹I-antiEGFR-BSA-PCL、¹³¹I-BSA-PCL、¹³¹I及相同体积的生理盐水。通过研究裸鼠体重、肿瘤体积、SPECT显像及组织病理学方法,观察纳米脂质体的抑瘤效果。结果 共聚焦实验显示,与BSA-PCL组相比,antiEGFR-BSA-PCL组细胞内绿色荧光较明显,其介导的胞吞效应显著。摄碘率实验中,LS180细胞对¹³¹I-antiEGFR-BSA-PCL的摄取率明显高于¹³¹I-BSA-PCL(t=2.77~5.40,P<0.01)。¹³¹I-antiEGFR-BSA-PCL组与¹³¹I-BSA-PCL组裸鼠肿瘤增殖均较慢,二者差异无统计学意义(P>0.05)。给药后72 h,¹³¹I-antiEGFR-BSA-PCL与¹³¹I-BSA-PCL的肿瘤摄取率分别为(21.61±1.01)和(20.58±0.65)% ID/g,均明显高于¹³¹I组(t=9.36、8.69,P<0.01)。SPECT显像显示纳米脂质体主要特异性积聚在肿瘤区。结论 ¹³¹I-antiEGFR-BSA-PCL对LS180结肠癌裸鼠移植瘤有明显的抑制作用。     

6家医院碘治疗场所工作人员甲状腺131I活度测量

目的调查碘治疗场所工作人员甲状腺131I活度水平及其主要影响因素。方法采用配额抽样的方法, 按照碘治疗场所医院的不同类型, 在山西省和山东省共选择6家开展碘治疗的医院, 采用直接测量法, 对76名碘治疗场所工作人员的甲状腺131I活度进行了测量, 并进行内照射剂量估算。结果共有5家医院的29人甲状腺131I活度高于仪器的探测限, 占全部被检测人员的38.16%, 其中最高值为2 468.45 Bq, 是1名负责手动分装放射性碘的医师。6家医院碘治疗场所工作人员甲状腺131I活度差异无统计学意义(P>0.05), 但手动分装131I的医院测量结果高于自动分装的医院, 差异有统计学意义(Z=1.75, P<0.01), 两家手动分装131I医院的12名碘治疗场所工作人员甲状腺测量结果全部高于探测限, 中位数分别为324.59 Bq和331.98 Bq, 4家使用自动分装仪的医院测量结果的中位数均低于探测限, 甲状腺131I检出率分别为32.61%、25.00%、10.00%和0。对于同一家医院, 参与分装131I的医生和保洁人员甲状腺131I活度高于不参与分装的医生, 差异有统...     

Non-invasive in vivo imaging with radiolabelled FIAU for monitoring cancer gene therapy using herpes simplex virus type 1 thymidine kinase and ganciclovir

An experimental cancer gene therapy model was employed to develop a non-invasive imaging procedure using radiolabelled 2'-fluoro-2'-deoxy-5-iodo-1--d-arabinofuranosyluracil (FIAU) as an enzyme substrate for monitoring retroviral vector-mediated herpes simplex virus type 1 thymidine kinase gene (HSV1-tk) transgene expression. Iodine-131 labelled FIAU was prepared by a no-carrier-added (n.c.a.) synthesis process and lyophilised to give "hot kits". The labelling yield was over 95%, with a radiochemical purity of more than 98%. The stability of [¹³¹I]FIAU in the form of lyophilised powder (the hot kit) was much better than that in the normal saline solution. The shelf life of the final [¹³¹I]FIAU hot kit product is as long as 4 weeks. Cellular uptake of [¹³¹I]FIAU after different periods of storage was investigated in vitro with HSV1-tk-retroviral vector transduced NG4TL4-STK and parental non-transduced NG4TL4 murine sarcoma cell lines over an 8-h incubation period. The NG4TL4-STK cells accumulated more radioactivity than NG4TL4 cells in all conditions, and accumulation increased with time up to 8 h. The kinetic profile of the cellular uptake of n.c.a. [¹³¹I]FIAU formulated from the lyophilised hot kit or from the stock solution was qualitatively similar. For animal model cancer gene therapy studies, FVB/N mice were inoculated subcutaneously with the HSV1-tk(+) and tk(–) sarcoma cells into the flank to produce tumours. Biodistribution studies showed that tumour/blood ratios were 2, 3.5, 8.2 and 386.8 at 1, 4, 8 and 24 h post injection, respectively, for the HSV1-tk(+) tumours, and 0.5, 0.5, 0.7 and 5.4, respectively, for the HSV1-tk(–) tumours. Radiotracer clearance from blood was completed in 24 h and was bi-exponential. A significant difference in radioactivity accumulation was revealed among the HSV1-tk(+) tumours, the tk(–) tumours and other tissues. At 24 h p.i., higher activity retention was observed in HSV1-tk(+) tumours (9.67%±3.89%ID/g) than in HSV1-tk(–) tumours (0.48%±0.19%ID/g). After seven consecutive daily treatments with the prodrug ganciclovir, planar gamma camera imaging showed HSV1-tk(+) tumour regression at day 4, and complete tumour regression at day 7. These results clearly demonstrate that the simplified n.c.a. synthesis process developed in this study is reliable and that the [¹³¹I]FIAU product is useful for in vivo monitoring of HSV1-tk gene transfer, expression and gene therapy.     

<Superscript>131</Superscript>I-MIBG Therapy in metastatic phaeochromocytoma and paraganglioma

Purpose ¹³¹Iodine metaiodobenzylguanidine (¹³¹I-MIBG) is a radiopharmaceutical used for scintigraphic localisation of phaeochromocytomas and paragangliomas. The experience with its therapeutic use is limited. We report our experience for the treatment of malignant phaeochromocytoma and paraganglioma. Materials and methods The charts of 19 patients with malignant phaeochromocytoma (n = 12) or paraganglioma (n = 7), who were treated with ¹³¹I-MIBG, were retrospectively reviewed. Four patients (21%) received radiotherapy, three (16%) chemotherapy, and in one patient (5%), both chemotherapy and radiotherapy was given before ¹³¹I-MIBG therapy. Response to ¹³¹I-MIBG treatment was evaluated by objective as tumour response, biochemical and subjective response. Results Of the 19 patients, 13 (68%) were men, 6 (32%) were women. Ages ranged from 22 to 68 years (median, 47). The median initial dose was 7.4 GBq (200 mCi; range, 6.7 GBq–25.9 GBq, 180–700 mCi); median cumulative dose was 22.2 GBq (600 mCi; range, 6.8 GBq–81.4 GBq, 183–2200 mCi). Objective tumour response was achieved in 47% of the patients. Biochemical response rate was 67%, and symptomatic response was seen in 89% of the patients. Overall median follow-up was 29 months, with a range of 3–93 months. Haematologic complications were the most common side effects and were observed in 26% of the patients. Conclusion Our data support that symptomatic and biochemical response can be reached with ¹³¹I-MIBG therapy in patients with metastatic phaeochromocytoma and paraganglioma. Although complete tumour response was not observed, the palliation and control of tumour function by ¹³¹I-MIBG therapy may be valuable for the patients.     

核医学场所空气中131I浓度监测及工作人员内照射剂量评价探讨

目的 了解医疗机构¹³¹I治疗工作场所空气中¹³¹I核素的活度浓度水平，探讨通过空气采样方法估算工作人员内照射剂量的方法并分析其影响因素。方法 选取郑州市10家开展¹³¹I核素治疗的工作场所，采用空气采样方法采集¹³¹I治疗工作场所中放射性气溶胶，用高纯锗γ能谱仪进行γ放射性核素测定并推算工作场所空气中¹³¹I核素的活度浓度水平，根据测量结果和现场调查结果估算放射工作人员因¹³¹I核素吸入导致的内照射剂量。结果 19个分装间空气样品的¹³¹I活度浓度为0.087~570 Bq/m³，平均为（51.04±128.58）Bq/m³；11个病房空气样品的¹³¹I活度浓度为0.162~54.6 Bq/m³，平均为（7.97±15.89）Bq/m³。根据GBZ 129-2016《职业性内照射个人监测规范》推荐的典型工作时间估算，放射工作人员由于吸入¹³¹I核素导致的年待积有效剂量范围为2 μSv~10 mSv，平均为（0.61±1.80）mSv，年有效剂量均未超过国家标准所规定的剂量限值。结论 郑州市10家医疗机构核医学工作场所中¹³¹I核素活度浓度较高的样品多分布在甲状腺癌住院患者较多、核素操作量较大的三甲医院，由此导致的工作人员内照射剂量不容忽视。根据空气样品的测量结果估算内照射剂量带有很大不确定度，但空气采样方法可及时发现异常或事故情况下的放射性污染，为工作人员开展体外直接测量和内照射评价提供预警。     

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.     

New cross-sections for production of Pd; review of charged particle production routes

Production cross-sections of ¹⁰³Ag obtained by irradiating ^natPd and ^natCd with 70 MeV protons are presented and compared with ALICE-IPPE model calculations. Production of ¹⁰³Ag is of interest for the generation of ¹⁰³Pd widely used in brachytherapy. The investigated energy range of the ¹⁰³Rh(d,2n)¹⁰³Pd reaction was extended up to 40 MeV and the results were compared with the curves of ALICE-IPPE, EMPIRE-II and GNASH theoretical codes. Thick target yields were calculated. An overview and analysis of the most important charged particle induced production routes of ¹⁰³Pd is presented. An explanation of the apparent discrepancy in the activity measurements for ¹⁰³Rh based on X- or gamma-ray is given.     

In vivo and in vitro studies into the immunological changes following iodine 131 therapy for Graves' disease

Radio-iodine therapy for Graves' disease is followed by immunological changes in addition to effects on thyroid hormone production. The present study examined these changes and the mechanisms responsible for them. Of the 15 patients enrolled in the study, 10 became hypothyroid in the first year after iodine 131 therapy. Patients who became hypothyroid had a tendency to show a rise in serum thyrotropin receptor antibody levels (30 ± 14 to 40 ± 9 units; NS) and a significant rise in immunoglobulin production (324 ± 153 to 740 ±200 ng/ml; P < 0.0005) from mitogen-stimulated peripheral blood lymphocytes (a measure of B-cell activity) 2 months after iodine 131 therapy. The increases were not seen in the patients who remained euthyroid at 1 year. In vitro studies suggested that the rise in B-cell activity is due to a fall in suppressor T cell numbers, a change shown to occur following iodine 131 therapy in previous studies. Our results indicate that immunological changes do arise after iodine 131 therapy for Graves' disease but appear to be confined to patients who subsequently became hypothyroid. It is not possible from this study to determine whether the immunological changes appear as a consequence of thyroidal destruction leading to hypothyroidism or whether they contribute directly to it. Offprint requests to: R. Wilson     

Local delivery of <Superscript>131</Superscript>I-MIBG to treat peritoneal neuroblastoma

Internal radiotherapy involving systemic administration of iodine-131 metaiodobenzylguanidine (¹³¹I-MIBG) in neural crest tumours such as neuroblastoma has shown considerable success. Although peritoneal seeding of neuroblastoma occurs less often than metastases to organs such as the liver, no effective treatments exist in this clinical setting. Previous reports have demonstrated the effectiveness of peritoneal application of chemotherapeutic drugs or radiolabelled monoclonal antibodies in several kinds of carcinomas. Local delivery of ¹³¹I-MIBG should produce more favourable dosimetry in comparison with its systemic administration in the treatment of peritoneal neuroblastoma. In the current investigation, a peritoneal model of neuroblastoma was established in Balb/c nu/nu mice by i.p. injection of SK-N-SH neuroblastoma cells. Two weeks after cell inoculation, comparative biodistribution studies were performed following i.v. or i.p. administration of ¹³¹I-MIBG. Mice were treated with 55.5 MBq of ¹³¹I-MIBG administered either i.v. or i.p. at 2 weeks. Intraperitoneal injection of ¹³¹I-MIBG produced significantly higher tumour accumulation than did i.v. injection (P<0.01). Therapeutic ratios of i.p. injection were 4- to 14-fold higher than those of i.v. injection. Radiotherapy with i.v. administered ¹³¹I-MIBG failed to improve the survival of mice; mean survival of untreated mice and mice treated with i.v. administration of ¹³¹I-MIBG was 59.3±3.9 days and 60.6±2.8 days, respectively. On the other hand, radiotherapy delivered via i.p. administration of ¹³¹I-MIBG prolonged survival of mice to 94.7±17.5 days (P<0.02 vs untreated controls and mice treated with i.v. ¹³¹I-MIBG therapy). Radiation doses absorbed by tumours at 55.5 MBq of ¹³¹I-MIBG were estimated to be 4,140 cGy with i.p. injection and 450 cGy with i.v. injection. These results indicate the benefits of locoregional delivery of ¹³¹I-MIBG in the treatment of peritoneal neuroblastoma.