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.     

90Y bremsstrahlung emission computed tomography using gamma cameras

Objective  This study demonstrates images obtained by ⁹⁰Y bremsstrahlung emission computed tomography (BECT), and characterizes the system performance of gamma cameras. Methods   ⁹⁰Y BECT images of phantoms were acquired using a gamma camera equipped with a medium energy general purpose parallel-hole collimator. Three energy window widths of 50% (57–94 keV) centered at 75 keV, 30% (102–138 keV) at 120 keV, and 50% (139–232 keV) at 185 keV were set on a ⁹⁰Y bremsstrahlung spectrum. The images obtained with three energy windows were reconstructed using filtered back projection (FBP) and ordered subsets expectation maximization (OSEM) methods. The images of the sum window were obtained by fusing the images of the 75, 120, and 185 keV windows. Results  The OSEM method improved the full width at half maximum by 20% and the standard deviation by 9% compared with the FBP method. BECT displayed ⁹⁰Y biodistribution and quantified ⁹⁰Y activity. BECT images obtained with OSEM method using the 120 keV window showed the highest resolution and lowest uncertainty. The sum window showed the highest sensitivity, while its resolution was 10% inferior to that of the 120 keV window. One whole-body image can be taken over 100 min using the sum window. An absorber to cover the body surface reduced background by 30%. Conclusions   ⁹⁰Y BECT imaging can be used for patient assessment without modifying current treatment procedures.     

90Y树脂微球选择性内放射治疗放射防护检测与剂量评估

目的对90Y树脂微球选择性内放射治疗过程进行放射防护检测和剂量评估,为放射防护工作提供参考。方法对90Y树脂微球介入手术治疗各操作环节和患者体表的外照射水平进行检测,估算相关人员的受照剂量水平。结果90Y树脂微球分装及转运过程的剂量率水平为1.12~454μSv/h,手术操作过程为2.06~58.2μSv/h;3名患者术后0.5 h,体表5 cm和1 m处的剂量率分别为22.7~64.1和0.82~2.55μSv/h。按照每年200例患者的工作量,90Y树脂微球药物操作对工作人员年个人有效剂量贡献为0.12~1.03 mSv/年,术后患者对公众、家属及陪护志愿者的个人有效剂量贡献为0.02~0.24 mSv/年。结论在患者治疗、护理和出院过程中,工作人员、陪护志愿者和公众的照射剂量均低于(GB 18871-2002«电离辐射防护与辐射源安全基本标准»)中的剂量限值和医疗机构设定的管理目标值。     

90Y树脂微球治疗患者尿液中90Y放射性活度检测和分析

目的研究患者接受90Y树脂微球选择性内放射治疗(SIRT)后48 h内所排泄尿液中90Y的放射性活度, 为术后患者排泄物的管理提供建议。方法收集3名患者在术后0～24 h和24～48 h两个时间段内排泄的尿液, 并对尿液中的90Y放射性活度进行检测和分析。结果 3名患者术后0～24 h和24～48 h尿液中的90Y放射性活度排泄量分别为(1 266±258)kBq/GBq和(140±106)kBq/GBq, 90Y放射性活度浓度分别为(640±113)kBq/L和(53±12)kBq/L。结论 90Y树脂微球治疗术后肝癌患者0～24 h排泄尿液中的90Y放射性活度比24～48 h高。术后患者可通过增加排泄尿量的方式来加速排出体内游离的90Y;患者住院期间的排泄物应按照HJ 1188-2020《核医学辐射防护与安全要求》的要求处理。     

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.     

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.     

[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.     

90Sr-90Y对人良性前列腺增生细胞增殖与凋亡影响的研究

目的探讨放射性核素     

Production of Cu using natural cobalt target and its separation using ascorbic acid and common anion exchange resin

⁶¹Cu was produced by ^natCo(α, xn)⁶¹Cu reaction. ⁶¹Cu production yield was 89.5 MBq/μAh (2.42 mCi/μAh) at the end of irradiation (EOI). A simple radiochemical separation method using anion exchange resin and ascorbic acid has been employed to separate the product radionuclide from inactive target material and co-produced non-isotopic impurities. The radiochemical separation yield was about 90%. Radiochemical purity of ⁶¹Cu was >99% 1 h after EOI. Final product was suitable for making complex with N₂S₂ type of ligands.     

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.     

钚锶对大鼠复合作用的实验研究

本文探讨低剂量硝酸钚与硝酸锶对大鼠复合作用的实验研究。系统观察了体重、死亡率, 平均存活时间、X线片、病理组织学等项目指标的改变。通过三年左右的终生观察表明: (1)钚、锶复合作用对诱发骨肉瘤有相加效应, 并且潜伏期短, 多发性骨肉瘤也高于单一核素作用组, (2)复合作用组的死亡率高于单一核素组, (8)复合作用组的平均寿命比单一核素组缩短。     

Production and first use of SmCl3-ion exchange resin capsule formulation for assessing gastrointestinal motility

We produced an enteric-coated gelatine capsule containing neutron-activated ¹⁵³Sm-labelled resin beads for use in gastrointestinal motility studies. In vitro test in simulated gastrointestinal environment and in vivo study on volunteers were performed. Scintigraphic images were acquired from ten volunteers over 24 h while blood and urine samples were collected to monitor the presence of ¹⁵³Sm. All the capsules remained intact in stomach. This proved to be a safe and practical oral capsule formulation for whole gut transit scintigraphy.     

Radioembolisation with <Superscript>90</Superscript>Y-microspheres: dosimetric and radiobiological investigation for multi-cycle treatment

Introduction  Radioembolisation with ⁹⁰Y-microspheres is a new locoregional treatment of hepatic lesions, usually applied as single cycle. Multi-cycle treatments might be considered as a strategy to improve the risk-benefit balance. With the aim to derive suitable information for patient tailored therapy, available patients’ dosimetric data were reviewed according to the linear–quadratic model and converted into biological effective dose (BED) values. Single vs. multi-cycle approaches were compared through radiobiological perspective. Materials and methods  Twenty patients with metastatic lesions underwent radioembolisation. The ⁹⁰Y-administered activity (AA) was established in order to respect a precautionary limit dose (40 Gy) for the non-tumoral liver (NTL). BED was calculated setting α/β = 2.5 Gy (NTL), 10 Gy (tumours); T _1/2,eff = T _1/2,phys = 64.2 h; T _1/2,rep = 2.5 h (NTL), 1.5 h (tumours). The BED to NTL was considered as a constraint for multi-cycle approach. The AA for two cycles and the percent variations of AA, tumour dose, BED were estimated. Results  In one-cycle, for a prescribed BED to NTL of 64 Gy (NTL dose = 40 Gy), AA was 1.7 (0.9–3.2) GBq, tumour dose was 130 (65–235) Gy, and tumour BED was 170 (75–360) Gy. Considering two cycles, ∼15% increase was found for AA and dose to NTL, with unvaried BED for NTL. Tumour dose increase was 20 (10–35) Gy; tumour BED increase was 10 (3–11) Gy. In different protocols allowing 80 Gy to NTL, the BED sparing estimated was ∼50 Gy (two cycles) and 65 Gy (three cycles). Conclusions  From a radiobiological perspective, multi-cycle treatments would allow administering higher activities with increased tumour irradiation and preserved radiation effects on NTL. Trials comparing single vs. multiple cycles are suggested.     

Toxicities after Radioembolization with Yttrium-90 SIR-Spheres: Incidence and Contributing Risk Factors at a Single Center

Purpose

To report the incidence of liver function test (LFT) toxicities after radioembolization with yttrium-90 (⁹⁰Y) SIR-Spheres and review potential risk factors.

Materials and Methods

Patients receiving ⁹⁰Y for radioembolization of primary or metastatic liver tumors had follow-up LFTs 29–571 days after treatment. The incidence and duration of bilirubin, aspartate aminotransferase (AST), and alanine aminotransferase (ALT) toxicities were documented using common terminology criteria. Factors that were assessed included previous intra-arterial (IA) therapy, systemic chemotherapy, low tumor-to-normal liver tissue ratio at mapping angiography, vascular stasis, and higher prescribed ⁹⁰Y doses.

Results

There were 81 patients who underwent 122 infusions and had follow-up LFTs. Of 122 infusions, 71 (58%) were associated with toxicity. One patient died with radiation-induced liver disease. Grade 3 or greater toxicities occurred in seven (7%) patients after nine procedures. The median durations of laboratory elevations for bilirubin, AST, and ALT were 29 days, 29 days, and 20 days. Toxicity developed after 51 (71%) of 72 infusions with previous IA therapy versus 20 (40%) of 50 infusions in treatment-naïve areas (P = .0006). Absence of previous systemic therapy was associated with greater risk of toxicity versus previous chemotherapy (47% vs 66%, P = .03). Other factors were not associated with increased toxicity.

Conclusions

Mild hepatotoxicity developed frequently after infusion of SIR-Spheres using the body surface area method, with normalization of LFTs in most patients. Grade 3 or greater toxicities were seen in < 10% of infusions. Toxicity was strongly associated with previous IA therapy.     

Long-term evaluation of renal toxicity after peptide receptor radionuclide therapy with <Superscript>90</Superscript>Y-DOTATOC and <Superscript>177</Superscript>Lu-DOTATATE: the role of associated risk factors

Purpose  Peptide receptor radionuclide therapy (PRRT) of neuroendocrine tumours with ⁹⁰Y-DOTATOC and ¹⁷⁷Lu-DOTATATE is promising. The kidney is the critical organ and despite renal protection, function loss may become evident years later. The aim of this study was to analyse renal parameters in patients who had undergone dosimetry before PRRT. Methods  Among those in protocols at our institution, 28 patients were considered: 23 received ⁹⁰Y-DOTATOC (3.8–29.2 GBq, median 12.2) and five received ¹⁷⁷Lu-DOTATATE (20.7–29.2 GBq, median 23.2). Patients were followed up after therapy for creatinine and creatinine clearance loss (CCL) for 3–97 months (median 30). Renal doses and bio-effective doses (BED) were calculated (MIRD, LQ model). Results  After ⁹⁰Y-DOTATOC toxicity on creatinine according to NCI criteria occurred in nine cases (seven grade 1, one grade 2, one grade 3), CCL at 1 year was >5% in 12 cases and >10% in eight. A 28-Gy BED threshold was observed in patients with risk factors (mainly hypertension and diabetes), while it was 40 Gy in patients without risk factors. Probably due to the low number of patients, despite the absence of severe toxicity after hyper-fractionated PRRT, clear correlations between fractionation and toxicity could not be found. After ¹⁷⁷Lu-DOTATATE, no toxicity occurred in 1–2 year follow-up; CCL at 1 year >5% occurred in three patients and >10% in two. Conclusions  Our results indicate the importance of clinical screening for risk factors: In this case, a BED <28 Gy is recommended. Fractionation of therapy is important in order to decrease toxicity, and further studies are needed to evaluate its clinical impact. An erratum to this article can be found at     

Yttrium-90 and indium-111 labelling, receptor binding and biodistribution of [DOTA0,d-Phe1,Tyr3]octreotide, a promising somatostatin analogue for radionuclide therapy

In vitro octreotide receptor binding of [¹¹¹In-DOTA⁰,d-Phe¹,Tyr³]octreotide (¹¹¹In-DOTATOC) and the in vivo metabolism of⁹⁰Y or¹¹¹In-labelled DOTATOC were investigated in rats in comparison with [¹¹¹In-DTPA⁰]octreotide [¹¹¹In-DTPAOC).¹¹¹In-DOTATOC was found to have an affinity similar to octreotide itself for the octreotide receptor in rat cerebral cortex microsomes. Twenty-four hours after injection of⁹⁰Y or¹¹¹In-labelled DOTATOC, uptake of radioactivity in the octreotide receptor-expressing tissues pancreas, pituitary, adrenals and tumour was a factor of 2–6 that after injection of¹¹¹In-DTPAOC. Uptake of labelled DOTATOC in pituitary, pancreas, adrenals and tumour was almost completely blocked by pretreatment with 0.5 mg unlabelled octreotide, indicating specific binding to the octreotide receptors. These findings strongly indicate that⁹⁰Y-DOTATOC is a promising radiopharmaceutical for radiotherapy and that¹¹¹In-DOTATOC is of potential value for diagnosis of patients with octreotide receptor-positive lesions, such as most neuroendocrine tumours.     

Clinical significance of 18F-FDG uptake by primary sites in patients with diffuse large B cell lymphoma in the head and neck: a pilot study

Objective  This pilot study was launched to explore the utility of positron emission tomography scans, at the time of diagnosis, for clinical outcomes in patients with primary extranodal non-Hodgkin’s lymphoma (PENHL) in the head and neck, retrospectively. Methods  Twenty-two patients with a diffuse large B cell lymphoma (DLBCL) among those with a PENHL were included. We retrospectively evaluated the clinical outcomes of patients according to the maximum standardized ¹⁸F-fluoro-2-deoxy-glucose (¹⁸F-FDG) uptake value of the primary lesion (SUV_p). The SUV_p was initially analyzed as a continuous variable. The cut-offvalue of SUV_p was obtained from receiver-operating characteristic analysis to predict event-free survival. Using this value, patients were divided into those with a low and high SUV. Results  Seventeen patients (59%) were men and the median age was 50 years. Most primary sites were in Waldeyer’s ring (73%). The SUV_p ranged from 3.3 to 23.7. The international prognostic index (IPI < 2 vs. ≥ 2) was associated with the SUV_p (P = 0.014). Patients with low SUV_p showed favorable survival (P = 0.015). After IPI scores were stratified, the survival difference remained significant (P = 0.029). Conclusions  The results of this pilot investigation indicate that ¹⁸F-FDG uptake of the primary lesion may be related with survival outcomes in patients with extranodal DLBCL in the head and neck. Further studies are needed to confirm and extend these results. I.I. Na and G.J. Cheon contributed equally to this work.     

Evaluation of uncertainty and detection limits in Pb and Po measurement in water by alpha spectrometry using Po spontaneous deposition onto a silver disk

An easy and accurate method for the determination of ²¹⁰Pb and ²¹⁰Po in water using ²¹⁰Po spontaneous deposition onto a silver disk is proposed and assessed for its detection capabilities according to the ISO Guide for the expression of uncertainty in measurement (GUM) and ISO Standard 11929-7 concerning the evaluation of the characteristic limits for ionizing radiation measurements. The method makes no assumption on the initial values of the activity concentrations of ²¹⁰Pb, ²¹⁰Bi and ²¹⁰Po in the sample to be analyzed, and is based on the alpha spectrometric measurement of ²¹⁰Po in two different aliquots: the first one measured five weeks after the sampling date to ensure radioactive equilibrium between ²¹⁰Pb and ²¹⁰Bi and the second after a sufficient time for the ingrowth of ²¹⁰Po from ²¹⁰Pb to be significant. As shown, for a recommended time interval of seven months between ²¹⁰Po measurements, the applicability of the proposed method is limited to water samples with a ²²⁶Ra to ²¹⁰Pb activity ratio C_Ra/C_Pb≤4, as usual in natural waters. Using sample and background counting times of 24 h and 240 h, respectively, the detection limit of the activity concentration of each radionuclide at the sampling time for a 1 L sample typically varies between 0.7 and 16 mBq L⁻¹ for ²¹⁰Pb in water samples with an initial activity of ²¹⁰Po in the range 0-200 mBq L⁻¹, and between 0.6 and 8.5 mBq L⁻¹ for ²¹⁰Po in water samples with an initial activity of ²¹⁰Pb in the same range.     

The detection and evaluation of drug-induced changes in the gastrointestinal motility of beagle dogs using a 111In-labelled resin mixed into a standard meal as tracer

An investigation was performed to establish the usefulness of ¹¹¹In-labelled polymer beads mixed into a standard meal as a tracer of gatrointestinal(GI)-motility changes due to the influence of various drugs. The labelled polymer beads were well mixed into the food, which was then fed to healthy beagle dogs undergoing drug therapy. GI motility was monitored using a gamma camera and data processor. The results were compared to those obtained from corresponding placebo studies on the same dogs. A significant acceleration of gastric emptying and colon transit was noted under the influence of a gastric and intestinal prokinetic coded R 51619. No influence on GI motility could, however, be detected after the administration of a calcium-blocking agent to the dogs.