Production of large quantities of 90Y by ion-exchange chromatography using an organic resin and a chelating agent

The performance of a system composed of an organic cation exchanger (Dowex 50Wx8) and a chelating agent (EDTA) previously described for the successful production of (90)Y via a (90)Sr/(90)Y generator is assessed under dynamic conditions. In an attempt to overcome the established limitation of ion-exchange resins for the separation of subcurie quantities of activity, (90)Y is repeatedly isolated from an 11.8-GBq (320 mCi) (90)Sr cow using a three-column tandem arrangement. The high recovery and radionuclidic purity obtained for (90)Y and the parameters of the separation (time, eluant concentration, pH and flow rate range) strongly suggest that Ci quantities of (90)Y can be handled satisfactorily by the ion-exchange method. No replacement or treatment of the cow, low waste generation and (90)Sr losses less than 0.1% after each run were observed during the present study which, in combination with the low cost of this resin, may result in an attractive alternate method for the production of large quantities of (90)Y.     

Comparison of calibration results for an extrapolation chamber obtained with different Sr+Y secondary standard sources

Two secondary standard systems of beta radiation were used to calibrate a PTW extrapolation chamber Model 23391. Three ⁹⁰Sr+⁹⁰Y sources of different activities were used in this calibration procedure. Medium-term stability of the response of the chamber was also studied. The calibration was performed with and without field-flattening filters. The relative standard deviation of the obtained calibration factors was 8.3% for the aluminum collecting electrode and 4.1% for the graphite collecting electrode.     

Thin CaSO4:Dy thermoluminescent dosimeters for calibration of Sr+Y applicators

Clinical applicators are used in brachytherapy to treat superficial lesions of skin and eye. They should be periodically calibrated according to quality control programs and international recommendations. Thin CaSO₄:Dy thermoluminescent dosimeters were used to calibrate various applicators with a dermatological applicator as a reference. The obtained absorbed dose rates were compared with those quoted in their calibration certificates. Depth-dose curves were constructed for all the applicators. A mail dosimetry system was developed for calibration of clinical applicators.     

90Y microsphere treatment of unresectable liver metastases: changes in 18F-FDG uptake and tumour size on PET/CT

Purpose The intra-arterial administration of ⁹⁰Y microspheres is a new palliative treatment option for unresectable liver metastases. The aim of this study was to quantitatively assess changes in FDG uptake and tumour size following ⁹⁰Y microsphere treatment (SIR-Spheres) using ¹⁸F-fluorodeoxyglucose (FDG) PET/CT imaging.Methods Five patients with unresectable liver metastases who had failed multiple prior chemotherapy regimens received seven ⁹⁰Y microsphere treatments to a single liver lobe. All patients underwent a baseline PET/CT scan prior to treatment, as well as up to four follow-up PET/CT scans. The tumour area of 30 liver metastases was measured on CT and the FDG uptake was semiquantitatively assessed by calculation of standardised uptake values (SUVs). A total of 18 FDG-PET/CT scans were performed.Results The SUVs in the 30 treated liver metastases decreased from 6.5±2.3 at baseline to 4.2±1.8 after the first follow-up PET/CT scan (p=0.001). In contrast, the SUVs of untreated metastases increased slightly from 7.2±2.3 to 8.0±0.8. There was no difference in FDG uptake in treated versus untreated normal liver tissue. Using a previously defined threshold of 20% decrease in SUV from baseline to determine response, 20 out of 30 liver metastases were considered to have responded at the first follow-up PET/CT scan approximately 1 month after treatment. In these metastases, the SUV decreased by 47±12%, compared with a slight increase by 5.9±19% in ten non-responding metastases (p=0.0001). The changes in tumour size did not correlate with changes in FDG uptake. On the first follow-up PET/CT scan, the tumour area on CT increased by 3.1±57% in treated metastases compared with 23.3±32% in untreated metastases. A wide range of post-treatment changes of target lesions was observed on CT, including an increase in the size of hypodense lesions, necrotic features and complete resolution of CT abnormalities.Conclusion The metabolic information obtained from FDG-PET/CT seems to provide a more accurate and earlier assessment of therapy response following ⁹⁰Y microsphere treatment than does the anatomical CT information.     

Sequential Use of 90Y Microspheres Radioembolization and 177Lu-Dotatate in Pluri-Metastatic Neuroendocrine Tumors: A Case Report

⁹⁰Y radioembolization and peptide-receptor radionuclide therapy (PRRT) with¹⁷⁷Lu-DOTATATE are both effective treatments for patients with inoperable neuroendocrine metastatic tumors (NET). We report the case of a 72-year-old man with severe functional syndrome due to a metastatic NET. ⁶⁸Ga-DOTATOC positron-emission tomography (PET) revealed high somatostatin receptor expression in a gross liver metastasis, in one abdominal lymph node and in several skeletal lesions. The patient underwent liver radioembolization with ⁹⁰Y-resin microspheres followed by four cycles of PRRT with¹⁷⁷Lu-DOTATATE. After 3 months, a complete remission of the functional syndrome was observed. ⁶⁸Ga-DOTATOC PET demonstrated a complete response for skeletal and lymph nodal lesions with a residual bulky mass in the liver. Therefore a further ⁹⁰Y radioembolization was performed as consolidation treatment for the hepatic lesion. Six months after these combined treatments, ⁶⁸Ga-DOTATOC PET demonstrated complete metabolic response in liver and stable extrahepatic lesions. No significant long-term adverse reactions were registered. To our knowledge, the sequential use of ⁹⁰Y radiembolization before and after PRRT in a liver-dominant advanced NET has not been reported in the literature and this case suggests that these combined treatments can be safe and effective.     

Sentinel lymph node accumulation of Lymphoseek and Tc-99m-sulfur colloid using a “2-day” protocol

Lymphoseek is a receptor-binding radiopharmaceutical specifically designed for sentinel lymph node (SLN) mapping. We conducted a clinical trial which measured the injection site clearance and sentinel lymph node accumulation after a single intradermal injection of Lymphoseek or unfiltered [^99mTc]sulfur colloid (TcSC) using a “2-day” protocol for SLN mapping of breast cancer. Eleven patients with breast cancer participated in this study. Five patients received an intradermal administration of 1.0 nmol of ^99mTc-labeled Lymphoseek; SLN mapping was performed on four subjects within 19 to 27 h. Six subjects received an intradermal administration of TcSC; SLN mapping was performed on five subjects within 18 to 26 h. Lymphoseek exhibited a significantly (P<.001) faster injection site clearance than TcSC. The mean Lymphoseek clearance half-time was 2.18±1.09 h compared to 57.4±92.8 h for TcSC. The mean sentinel lymph node uptake of Lymphoseek (1.5±1.7%) and TcSC (3.5±3.1%) was statistically equivalent (P=.213). When an intradermal injection is employed, Lymphoseek demonstrated faster injection site clearance than unfiltered [^99mTc]sulfur colloid and persistent SLN accumulation for at least 24 h.     

Application of “wet” extrapolation method for activity standardisation of electron capture radionuclides

The activity of electron capture radionuclides is usually determined by 4π(proportional counter, PC)–γ coincidence counting. The corrections necessary for the final activity value calculation are obtained by an extrapolation method. Variation of the PC detection efficiency can be achieved through different methods, e.g. by changing the self-absorption of the source using absorbing foils or by adding carriers. Another possibility is a “wet” extrapolation method, which utilises an absorption change during the drying of a water droplet added onto the source surface. In this paper, slopes of extrapolation curves and resulting activity values obtained by different methods are compared for several radionuclides (⁵⁴Mn, ¹³⁹Ce, ⁸⁸Y, ⁵⁷Co). In some cases a digital coincidence system was used for the analysis of measured data. The “wet” extrapolation, due to its very simple procedure, seems to be convenient for routine measurement and its accuracy is similar to the other methods.     

90Sr in Chinese tea of typical regions: activity concentration and hygienic evaluation

Objective To investigate the activity concentration of ⁹⁰Sr in tea produced in Chinese typical regions, enrich the baseline data for ⁹⁰Sr level in Chinese tea, and evaluate possible exposure doses to people. Methods Samples were carbonized, ashed, digested and leached, and then extraction chromatography method was used to separate ⁹⁰Sr and ⁹⁰Y. After preparation of sample source, radioactivity of ⁹⁰Y was measured using low-level α/β counter. Results Twenty six kinds of tea produced in 16 typical regions from 26 cities of 16 provinces were collected in 2016, and their ⁹⁰Sr activity concentrations were analyzed using the separation method of di(2-ethylhexyl) phosphate (HDEHP) extraction chromatography. The results revealed that the activity concentrations in 26 kinds of tea samples ranged from 0.28 to 3.78 Bq/kg, and contributed possible exposure doses of 0.44×10^-2- 6.00×10^-2 μSv to each people. Conclusions These doses were far less than the ICRP annual dose limit of 1 mSv for the public, suggesting less impact on people''s health.     

[111In]DOTATOC as a dosimetric substitute for kidney dosimetry during [90Y]DOTATOC therapy: results and evaluation of a combined gamma camera/probe approach

Purpose During [⁹⁰Y]DOTATOC therapy, for determination of kidney doses a conventional approach using co-injected [¹¹¹In]DOTATOC was evaluated for validity, reliability and reproducibility as well as for the influence of methodological variations and bremsstrahlung. Biologically effective doses were estimated by calculating the relative effectiveness (RE) of kidney doses.Methods Fractionated [⁹⁰Y]DOTATOC therapy (n=20 patients, 3.1±0.7 GBq/therapy cycle, 45 therapy cycles) included co-injection of 157±37 MBq [¹¹¹In]DOTATOC and a nephroprotective infusion regimen. From serial gamma camera/probe measurements, individual region of interest (ROI) sets were established and kidney doses were determined according to MIRDOSE3 (corrected for individual kidney mass) by use of three methodological variants: (1) correction for interfering organs (liver/spleen) and background activity, (2) correction for interfering organs alone and (3) no corrections. A phantom study was performed with ¹¹¹ In alone and with ¹¹¹In +⁹⁰Y to estimate the influence of ⁹⁰Y bremsstrahlung.Results Mean kidney dose (method 1, n=20 patients, 20 therapy cycles) was 1.51±0.60 Gy/GBq [⁹⁰Y]DOTATOC (1.41±0.48 Gy/GBq for n=20 patients, 45 therapy cycles). With partial correction (method 2) or no correction (method 3) for interfering activity, kidney doses increased significantly, to 2.71±1.26 Gy/GBq and 3.15±1.22 Gy/GBq, respectively. The span of REs ranged from 1.02 to 1.24. Inter-observer variability was as high as ±32% (±2SD). ⁹⁰Y bremsstrahlung accounted for a 4–11% underestimation of obtained target activity.Conclusion The obtained kidney doses are highly influenced by methodological variations. Full correction for interfering activity clearly underestimates kidney doses. By comparison, ⁹⁰Y bremsstrahlung and variability in the relative effectiveness of kidney doses cause minor bias. Inter-observer variability must be considered when interpreting kidney doses.     

Implementation facilitation of the “11 for Health in Denmark”: A case study in a Danish 5th grade class

The “11 for Health in Denmark” concept aims to enhance 10–12-year-old schoolchildren's physical activity levels and health knowledge through an 11-week football intervention and has been shown to induce positive effects in numerous areas. However, little is known about the implementation facilitation of this concept in schools. This case study therefore aims to gain a deeper understanding of the implementation facilitation of “11 for Health” in a Danish 5^th grade class comprising 22 schoolchildren (12 boys and 10 girls, M_age 11.86±) and one teacher. Data were derived from multiple school situations using photographs and videos, observations, and informal interviews. Five themes were identified: (1) environmental and organizational factors impacting on the implementation; (2) familiarization with the concept for the teacher and schoolchildren; (3) previous clique formation; (4) the central role of the teacher; and (5) the importance of how praise partners are allocated. We found high adherence to the “11 for Health” concept, in which the teacher played a key role by applying an autonomy-supportive style of teaching and using the praise partner concept in a suitable manner. A clique of football-playing boys was a resource, as their praising of classmates encouraged adherence. However, familiarization with the “11 for Health” concept was a challenge and the clique's competitive nature occasionally built barriers to other schoolchildren without football experience, potentially leading to a more controlled form of motivation. Based on the results, we encourage teachers to apply autonomy-supportive teaching when applying the “11 for Health” concept.     

Accuracy of plasma sample methods for determination of glomerular filtration rate with<Superscript>99m</Superscript>Tc-DTPA

The plasma sample method following a single injection of radioactive markers has been proved to be simple and accurate for the determination of glomerular filtration rate (GFR) in clinical practice. The aim of this study was to assess clinical accuracy of single-, two- and multi-sample methods. METHODS: The study was performed on 50 patients with various degrees of renal dysfunction (29 males and 21 females; aged 27 to 90 years). As a reference the true GFR (GFRt) was determined by means of the two-compartment model curve fitting 10 plasma samples following a single-injection of 99mTc-DTPA. The GFRt was compared to the GFR estimated by the Christensen and Groth's single-sample (GFRcg), two-sample (GFR2s) and multi-sample (GFRm) between 75 and 300 min after the injection. The GFRs by two- and multi-sample methods were determined with the slope and intercept algorithm and its overestimation was corrected by Brochner-Mortensen's formula. RESULTS: In 49 patients with GFR between 12 and 169 ml/min/1.73 m2, the standard deviation of difference (95% limits of agreement) between GFRt and GFRcg at 180 min was 6.513 ml/min/l73 m2 (-16.5 approximately 9.5 ml/min/1.73 m2), which was somewhat closer than 7.311 ml/min/1.73 m2 (-12.5 approximately 16.5 ml/min/1.73 m2) in GFR2s in slow clearance phase at 120 min and 240 min. However, the single-sample method tended to show some scattering in GFR below 30 and above 140 ml/min/ 1.73 m2. On the contrary, the 2-sample method tended to be scattered in GFR above 120 ml/min/ 1.73 m2. CONCLUSION: In view of its accuracy and technical simplicity, the single-sample method is first choice in a routine practice. The two-sample method is essential of choice for a patient in whom the GFR is expected to be below 30 ml/min/1.73 mi2. These two methods may be chosen selectively in dependence on the preserved renal function which is expected at time of the test.     

ICP-MS法分析尿中总铀和235U/238U比值及其不确定度评价

目的 建立电感耦合等离子体质谱（ICP-MS）快速测量尿中总铀含量和²³⁵U/²³⁸U比值的方法,并进行不确定度评价。方法 尿样经浓HNO₃和H₂O₂处理后,一部分定容直接进入ICP-MS测定总铀含量;一部分经磷酸三丁酯（TBP）萃淋树脂分离富集铀,采用ICP-MS测定其中²³⁵U/²³⁸U比值。以人尿样为例,通过样品前处理、测量、标准曲线计算,建立数学模型分析总铀及²³⁵U/²³⁸U比值的不确定度来源,进行不确定度合成。结果 该方法分析尿中总铀加标回收率为98.4%~102.4%,方法检出限为0.002 μg/L。经过不确定度评价,尿样中总铀含量的相对扩展不确定度为 0.26（k=2）;²³⁵U/²³⁸U比值的相对扩展不确定度为0.001 1（k=2）。结论 该方法加标回收率高,检出限低,精密度较好,能够实现尿中总铀的定量和²³⁵U/²³⁸U比值的快速分析,适用于放射职业照射或核应急的公众照射中尿铀及²³⁵U/²³⁸U比值的分析;尿中总铀及²³⁵U/²³⁸U比值不确定度评定结果准确可靠。     

The value of <Superscript>18</Superscript>F-Choline PET/CT in patients with elevated PSA-level and negative prostate needle biopsy for localisation of prostate cancer

Purpose Patients with persistent elevated PSA and repeated negative prostate biopsy, that means having the prostate biopsied at multiple times, were investigated with 18F-choline PET/CT to delineate prostate cancer and guide renewed prostate biopsy. Methods Twenty patients with elevated PSA and negative prostate biopsies underwent 18F-choline PET/CT. We performed an early examination of the pelvic region 3-5 min after application. After 30 minutes a whole body PET/CT examination was performed. Image analysis was performed visually and by semi-quantitative analysis calculating the maximum standardised uptake value (SUVmax). 18F-choline uptake was defined as focal, multifocal or inhomogeneous. After the 18F-choline PET/CT, all patients underwent a repeated prostate biopsy, and in the cases where a focal or multifocal uptake was found, the biopsy was guided by the result of the examination. Results Qualitative image analysis revealed focal 18F-choline uptake in 13 out of 20 patients. In five patients, prostate cancer was revealed by repeated aspiration biopsy. None of the patients with a multifocal or inhomogeneous 18F-choline uptake had a malignant neoplasm in the prostate. Semiquantitative analysis performed with SUVmax was not helpful in the discrimination of malignancy but showed high values also in benign prostate diseases, as well as in normal prostate tissue. The dual-phase protocol delivered no clear benefit in discriminating malignancy from benign alterations. Conclusion The use of 18F-choline cannot be generally recommended for localising prostate cancer; however, in highly selected patients, we found useful additional information. In 25% of patients, 18F-choline PET/CT allowed the identification of neoplastic prostatic zones.     

Usefulness of rate of increase in SPECT counts in one-day method of <Emphasis Type="Italic">N</Emphasis>-isopropyl-4-iodoamphetamine [<Superscript>123</Superscript>I] SPECT studies at rest and after acetazolamide challenge using a method for estimating time-dependent distribution at rest

OBJECTIVE: When N-isopropyl-4-iodoamphetamine ((123)I-IMP) single-photon emission computed tomography (SPECT) studies at rest and after acetazolamide (ACZ) challenge are conducted in a day, the time-dependent change in IMP in the brain at rest should be estimated accurately. We devised the method and investigated whether our one-day method for measuring the rate of increase in SPECT counts allowed reduction in the acquisition time. METHODS: Sequential, 5-min SPECT scans were performed. We estimated the time-dependent change in the brain using the change in slopes of two linear equations derived from the first three SPECT counts. For the one-day method, ACZ was administered 15 min or 20 min after IMP administration. The second IMP was administered 10 min after ACZ administration. RESULTS: Time-dependent changes in the brain were classified into 13 patterns when estimation was started at 5 min after IMP administration and 6 patterns when estimation was started at 10 min, and fitting coefficients were determined. The correlation between actual measurements at 37.5 min and estimates was high with a correlation coefficient of 0.99 or greater. Rates of increase obtained from 20-min data were highly correlated with those obtained from 15-min or 10-min data (r = 0.97 or greater). In patients with unilateral cerebrovascular disease, the rate of increase on the unaffected side was 44.4 +/- 10.9% when ACZ was administered 15 min later and 48.0 +/- 16.0% when ACZ was administered 20 min later, and the rates of increase with different timings of administration were not significantly different. CONCLUSIONS: The examination time may be reduced from 50 min to 45 min or 40 min as needed. The rate of increase was not influenced by the time frame for determination or the timing of ACZ administration. These findings suggest that our estimation method is accurate and versatile.     

Assessment of various strategies for <Superscript>18</Superscript>F-FET PET-guided delineation of target volumes in high-grade glioma patients

Purpose  The purpose of the study is to assess the contribution of ¹⁸F-fluoro-ethyl-tyrosine (¹⁸F-FET) positron emission tomography (PET) in the delineation of gross tumor volume (GTV) in patients with high-grade gliomas compared with magnetic resonance imaging (MRI) alone. Materials and methods  The study population consisted of 18 patients with high-grade gliomas. Seven image segmentation techniques were used to delineate ¹⁸F-FET PET GTVs, and the results were compared to the manual MRI-derived GTV (GTV_MRI). PET image segmentation techniques included manual delineation of contours (GTV_man), a 2.5 standardized uptake value (SUV) cutoff (GTV_2.5), a fixed threshold of 40% and 50% of the maximum signal intensity (GTV_40% and GTV_50%), signal-to-background ratio (SBR)-based adaptive thresholding (GTV_SBR), gradient find (GTV_GF), and region growing (GTV_RG). Overlap analysis was also conducted to assess geographic mismatch between the GTVs delineated using the different techniques. Results  Contours defined using GTV_2.5 failed to provide successful delineation technically in three patients (18% of cases) as SUV_max< 2.5 and clinically in 14 patients (78% of cases). Overall, the majority of GTVs defined on PET-based techniques were usually smaller than GTV_MRI (67% of cases). Yet, PET detected frequently tumors that are not visible on MRI and added substantially tumor extension outside the GTV_MRI in six patients (33% of cases). Conclusions  The selection of the most appropriate ¹⁸F-FET PET-based segmentation algorithm is crucial, since it impacts both the volume and shape of the resulting GTV. The 2.5 SUV isocontour and GF segmentation techniques performed poorly and should not be used for GTV delineation. With adequate setting, the SBR-based PET technique may add considerably to conventional MRI-guided GTV delineation.