Radiation doses of yttrium-90 citrate and yttrium-90 EDTMP as determined via analogous yttrium-86 complexes and positron emission tomography

Yttrium-90 is used for palliative therapy for the treatment of skeletal metastases, but because it is a pure - emitter, data on the pharmacokinetics and radiation doses to metastases and unaffected organs are lacking. To obtain such data, the present study employed yttrium-86 as a substitute for⁹⁰Y, with detection by positron emission tomography (PET). The study compared the properties of two different⁸⁶Y complexes —⁸⁶y-citrate and⁸⁶Y -ethylene diamine tetramethylene phosphonate (EDTMP) — in ten patients with prostatic cancer who had developed multiple bone metastases (the ten patients being divided into two groups of five). Early dynamics were measured up to 1 h post injection (p.i.) over the liver region, followed by subsequent whole-body PET scans up to 3 days p.i. Absolute uptake data were determined for normal bone, bone metastases, liver and kidney. Radiation doses were calculated according to the MIRD recommendations. Based on the pharmacokinetic measurements of the distribution of the⁸⁶Y complexes, it was possible to calculate radiation doses for the bone metastases and the red bone marrow delivered by complexes containing⁹⁰Y. In 1 cm³ of bone metastasis, doses of 26±11 mGy/MBq and 18±2 mGy/MBq were determined per MBq of injected⁹⁰Y- citrate and⁹⁰Y- EDTMP, respectively. The doses to the bone marrow were 2.5±0.4 mGy/MBq for⁹⁰Y- citrate and 1.8±0.6 mGy/MBq for⁹⁰Y-EDTMP.⁸⁶Y and PET provide quantitative information applicable to the clinical use of⁹⁰Y. This method may also be useful for the design of other⁹⁰Y radiopharmaceuticals and for planning radiotherapy dosages.     

Radiographic Response to Yttrium-90 Radioembolization in Anterior Versus Posterior Liver Segments

The purpose of our study was to determine if preferential radiographic tumor response occurs in tumors located in posterior versus anterior liver segments following radioembolization with yttrium-90 glass microspheres. One hundred thirty-seven patients with chemorefractory liver metastases of various primaries were treated with yttrium-90 glass microspheres. Of these, a subset analysis was performed on 89 patients who underwent 101 whole-right-lobe infusions to liver segments V, VI, VII, and VIII. Pre- and posttreatment imaging included either triphasic contrast material-enhanced CT or gadolinium-enhanced MRI. Responses to treatment were compared in anterior versus posterior right lobe lesions using both RECIST and WHO criteria. Statistical comparative studies were conducted in 42 patients with both anterior and posterior segment lesions using the paired-sample t-test. Pearson correlation was used to determine the relationship between pretreatment tumor size and posttreatment tumor response. Median administered activity, delivered radiation dose, and treatment volume were 2.3 GBq, 118.2 Gy, and 1,072 cm³, respectively. Differences between the pretreatment tumor size of anterior and posterior liver segments were not statistically significant (p = 0.7981). Differences in tumor response between anterior and posterior liver segments were not statistically significant using WHO criteria (p = 0.8557). A statistically significant correlation did not exist between pretreatment tumor size and posttreatment tumor response (r = 0.0554, p = 0.4434). On imaging follow-up using WHO criteria, for anterior and posterior regions of the liver, (1) response rates were 50% (PR = 50%) and 45% (CR = 9%, PR = 36%), and (2) mean changes in tumor size were −41% and −40%. In conclusion, this study did not find evidence of preferential radiographic tumor response in posterior versus anterior liver segments treated with yttrium-90 glass microspheres. Disclosure: R.S. is a consultant for MDS Nordion and has disclosed a potential conflict of interest. None of the other authors have disclosed a conflict. The data were controlled by all authors. No industry support for this study was provided.     

Radioembolization with Yttrium-90 resin microspheres in treatment of HCC with or without PVT: Initial Egyptian experience

Background/Aim

Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver. Radioembolization with yttrium-90 (Y-90) microspheres is a new concept in radiation therapy for HCC. The aim of this study is to evaluate efficacy, side effects, and future direction of Y-90 therapy, using TheraSphere®, in patients with HCC with or without PVT.

Patients and methods

Forty patients were presented by hepatocellular carcinoma most of them with portal vein thrombosis and were treated with Y-90 resin microspheres (SIR-TeX®).

Results

At one month after treatment the overall response (complete or partial response) was exhibited by 9% of patients, stable disease exhibited by 80% of patients, progressive disease seen in 11% of patients.

Conclusion

Radioembolization with Y-90 resin microspheres offers a favorable risk/benefit profile for patients presenting with locally advanced unresectable HCC with or without PVT and good liver function.     

Complications after 90Y microsphere radioembolization for unresectable hepatic tumors: An evaluation of 112 patients

PurposeThe aim of this study was to estimate the incidence of complications after ⁹⁰Y microsphere radioembolization for unresectable hepatic tumors and evaluate risk factors for late complications.Methods and MaterialsA cohort of 112 consecutive patients from two institutions underwent ⁹⁰Y microsphere radioembolization for unresectable hepatic tumors. Complications were graded according to the Common Terminology Criteria for Adverse Events, version 3.0. Symptoms secondary to postradioembolization syndrome occurring within 30 days were recorded as early complications, and all other complications were considered late complications.ResultsSeventy-eight patients (70%) experienced postradioembolization syndrome, including fatigue, abdominal pain, nausea, vomiting, anorexia, or fever. Three patients (3%) experienced a Grade 3 early complication; no Grade 4 or 5 early toxicity occurred. Two patients (2%) experienced clinically significant liver dysfunction; 13 patients (12%), 27 patients (24%), and 9 patients (8%) had an elevation of bilirubin, aspartate aminotransferase, and alanine aminotransferase, respectively. Eleven patients (10%) experienced gastrointestinal ulceration, including two Grade 3 complications and one Grade 4 complication. Cholecystitis occurred in 7 patients (6%), including two Grade 3 complications. Grade 2 pancreatitis occurred in 1 patient (1%). No radiation pneumonitis was observed. The cumulative incidence of late Grade 3 or 4 complications at 12 months after radioembolization was 8%. No Grade 5 toxicity occurred.Conclusions⁹⁰Y microsphere radioembolization is a well-tolerated treatment for unresectable hepatic tumors with a low risk of Grade 3 or higher early or late toxicity.     

Partition model for estimating radiation doses from yttrium-90 microspheres in treating hepatic tumours

A uniform distribution of yttrium-90 (⁹⁰Y) microspheres throughout the entire liver has always been assumed for dose calculation in treating hepatic tumours. A simple mathematical model was formulated which allows estimation of the activities of a therapeutic dose of⁹⁰Y microspheres partitioned between the lungs, the tumour and the normal liver, and hence the radiation doses to them. The doses to the tumour and normal liver were verified by intra-operative direct beta-probing. The percentage of activity shunted to the lung and the tumour-to-normal tissue ratio (T/N) were obtained from gamma scintigraphy using technetium-99m-labelled macroaggregated albumin (MAA) which simulates the⁹⁰Y microspheres used in subsequent treatment. The intrahepatic activity was partitioned between the tumour and the normal liver based on the T/N and their masses determined from computerized tomography slices. The corresponding radiation doses were computed using the MIRD formula. The estimated radiation doses were correlated with the doses directly measured using a calibrated beta-probe at laparotomy by linear regression. The radiation doses to the tumour and the normal liver, estimated using the partition model, were close to that measured directly with coefficients of correlation for linear regression: 0.862 for the tumours and 0.804 for the normal liver compartment (P<0.001). The partition model permits a distinction between the radiation doses received by the tumour and the normal liver to be made and the doses thus estimated are close to the actual doses received. The optimal doses to the tumour and normal liver and hence the required quantity of⁹⁰Y microspheres to be administered can be easily predetermined.     

90Y树脂微球治疗在临床应用中的放射防护研究

目的 探讨⁹⁰Y树脂微球治疗在临床应用中的放射防护措施。方法 模拟⁹⁰Y树脂微球治疗手术流程,通过监测术前药物分装准备、药物转运、术中药物操作和输注、术后患者住院观察各个阶段周围剂量当量率水平,分析临床应用中所应采取的放射防护措施。结果 活性室周围剂量当量率水平为0.12~0.42 μSv/h,通风橱周围剂量当量率为1.04~3.32 μSv/h。数字减影血管造影(DSA)室在⁹⁰Y+DSA扫描时最高为0.78 μSv/h,在⁹⁹Tc^m+DSA时最高为 0.36 μSv/h; 透视防护区在⁹⁰Y药物时在第一术者位155 cm高度为13.19 μSv/h,而在⁹⁰Y+DSA扫 描时最高为80 cm高度处315.01 μSv/h。第二术者位在⁹⁰Y药物时最高为155 cm高度为6.28 μSv/h, ⁹⁰Y+DSA 扫描时最高为155 cm高度处291.03 μSv/h。患者病房周围剂量当量率为0.11~0.58 μSv/h。 结论 核医学科及介入室等原有屏蔽措施能够满足⁹⁰Y树脂微球治疗的放射防护要求,但仍需根据实际情况进行科学评估,同时应加强药物操作中的放射防护及表面污染处理措施。     

Radioembolization with 90Y Microspheres: Angiographic and Technical Considerations

The anatomy of the mesenteric system and the hepatic arterial bed has been demonstrated to have a high degree of variation. This is important when considering pre-surgical planning, catheterization, and trans-arterial hepatic therapies. Although anatomical variants have been well described, the characterization and understanding of regional hepatic perfusion in the context of radioembolization have not been studied with great depth. The purpose of this review is to provide a thorough discussion and detailed presentation of the angiographic and technical aspects of radioembolization. Normal vascular anatomy, commonly encountered variants, and factors involved in changes to regional perfusion in the presence of liver tumors are discussed. Furthermore, the principles described here apply to all liver-directed transarterial therapies. R.S. and J.-F.G. are consultants for MDS Nordion. R.M., D.L., L.B., and J.I.B. are proctors for Sirtex Medical. A.S.K. has received honoraria from MDS Nordion and Sirtex Medical. This work was not funded.     

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.     

Three-step radioimmunotherapy with yttrium-90 biotin: dosimetry and pharmacokinetics in cancer patients

. A three-step avidin-biotin approach has been applied as a pretargeting system in radioimmunotherapy (RIT) as an alternative to conventional RIT with directly labelled monoclonal antibodies (MoAbs). Although dosimetric and toxicity studies following conventional RIT have been reported, these aspects have not previously been evaluated in a three-step RIT protocol. This report presents the results of pharmacokinetic and dosimetric studies performed in 24 patients with different tumours. Special consideration was given to the dose delivered to the red marrow and to the haematological toxicity. The possible additive dose to red marrow due to the release of unbound yttrium-90 was investigated. The protocol consisted in the injection of biotinylated MoAbs (first step) followed 1 day later by the combined administration of avidin and streptavidin (second step). After 24 h, biotin radiolabelled with 1.85–2.97 GBq/m² of ⁹⁰Y was injected (third step). Two different chelating agents, DTPA and DOTA, coupled to biotin, were used in these studies. Indium-111 biotin was used as a tracer of ⁹⁰Y to follow the biodistribution during therapy. Serial blood samples and complete urine collection were obtained over 3 days. Whole-body and single-photon emission tomography images were acquired at 1, 16, 24 and 40 h after injection. The sequence of images was used to extrapolate ⁹⁰Y-biotin time-activity curves. Numerical fitting and compartmental modelling were used to calculate the residence time values (τ) for critical organs and tumour, and results were compared; the absorbed doses were estimated using the MIRDOSE3.1 software. The residence times obtained by the numerical and compartmental models showed no relevant differences (<10%); the compartmental model seemed to be more appropriate, giving a more accurate representation of the exchange between organs. The mean value for the τ in blood was 2.0±1.1 h; the mean urinary excretion in the first 24 h was 82.5%±10.8%. Without considering any contribution of free ⁹⁰Y, kidneys, liver, bladder and red marrow mean absorbed doses were 1.62±1.14, 0.27±0.23, 3.61±0.70 and 0.11±0.05 mGy/MBq, respectively; the effective dose was 0.32±0.06 mSv/MBq, while the dose to the tumour ranged from 0.62 to 15.05 mGy/MBq. The amount of free ⁹⁰Y released after the injection proved to be negligible in the case of ⁹⁰Y-DOTA-biotin, but noteworthy in the case of ⁹⁰Y-DTPA-biotin (mean value: 5.6%±2.5% of injected dose), giving an additive dose to red marrow of 0.18±0.08 mGy per MBq of injected ⁹⁰Y-DTPA-biotin. Small fractions of free ⁹⁰Y originating from incomplete radiolabelling can contribute significantly to the red marrow dose (3.26 mGy per MBq of free ⁹⁰Y) and may explain some of the high levels of haematological toxicity observed. These results indicate that pretargeted three-step RIT allows the administraton of high ⁹⁰Y activities capable of delivering a high dose to the tumour and sparing red marrow and other normal organs. Although ⁹⁰Y-biotin clears rapidly from circulation, the use of DOTA-biotin conjugate for a stable chelation of ⁹⁰Y is strongly recommended, considering that small amounts of free ⁹⁰Y contribute significantly in increasing the red marrow dose. Received 6 June and in revised form 19 September 1998     

Preparation and biodistribution of yttrium-90 Lipiodol in rats following hepatic arterial injection

In this study, we labelled Lipiodol with yttrium-90 and analysed the biodistribution in rats after intrahepatic arterial injection. An RP-18 column (E. Merck) was used to separate⁹⁰Y from strontium-90.⁹⁰Y was retained on the column, which had been pretreated with yttrium-selective extraction reagent, di(2-ethylhexyl) phosphate, while⁹⁰Sr was washed out. A hexadentate nitrogen-donor chelating ligandN,N,N,N-tetrakis(2-ben-zymidazolylmethyl)-1,2-ethanediamine (EDTB) was synthesized by condensation of 1,2-benzenediamine and ethylene diamine tetra-acetic acid (EDTA). Lipiodol was covalently conjugated with EDTB. The final product was obtained by eluting the retained⁹⁰Y from the RP-18 column with EDTB-Lipiodol. Sixteen male rats (Sprague-Dawley) were sacrificed at 1 h, 24 h, 48 h and 72 h (four rats at each time) after injection of approximately 0.1 mCi⁹⁰Y Lipiodol via the hepatic artery. Samples of liver, spleen, muscle, lung, kidney, bone, whole blood and testis were obtained and counted to calculate the tissue concentrations. In addition, labelling efficiency and in vitro stability were determined by ITLC methods. We found that at 1 h after intrahepatic injection, most of the radiotracer was retained in the liver, but it was eliminated gradually over a few days. The radioactivity level in the lung was fair at 1 h and remained at roughly the same level throughout the study. Radioactivity in the kidney and spleen reached a relatively high level at 24 h, but declined rapidly. Bone uptake was low initially but showed an increase between 24 h and 72 h. Low concentrations of radioactivity were noted in the muscle, testis and whole blood. In the study of in vitro stability, radiochemical purity and labelling efficiency were higher than 90%, indicative of good stability. These initial results indicate that Lipiodol may be a possible carrier agent for⁹⁰Y The retention of⁹⁰Y-Lipiodol in the normal liver is high initially; however, elimination occurs over a period of a few days. Future studies should assess the biodistribution of⁹⁰Y Lipiodol in an animal model with liver cancer.     

Clinical evaluation of the partition model for estimating radiation doses from yttrium-90 microspheres in the treatment of hepatic cancer

Radiation doses to the tumour and non-tumorous liver compartments from yttrium-90 microspheres in the treatment of hepatic cancer, as estimated by a partition model, have been verified by correlation with the actual doses measured with a beta probe at open surgery. The validity of the doses to the lungs, the tumour and non-tumorous liver compartment as estimated by the partition model was further evaluated in clinical settings. On the basis of the observation that one of three patients who received more than 30 Gy from a single treatment and one of two patients who received more than 50 Gy from multiple treatments developed radiation pneumonitis, it was deduced that an estimated lung dose <30 Gy from a single treatment and a cumulative lung dose <50 Gy from multiple treatments were probably the tolerance limits of the lungs. Three of five patients who received lung doses >30 Gy as estimated by the partition model and were predicted to develop radiation pneumonitis, did so despite the use of partial hepatic embolization to reduce the degree of lung shunting. Furthermore, a higher radiological response rate and prolonged survival were found in the group of patients who received higher tumour doses, as estimated by the partition model, than in the group with lower estimated tumour doses. Thus the radiation doses estimated by the partition model can be used to predict (a) complication rate, (b) response rate and (c) duration of survival in the same manner as the actual radiation doses measured with a beta probe at open surgery. The partition model has made selective internal radiation therapy using⁹⁰Y microspheres safe and repeatable without laparotomy.     

Cherenkov counting of yttrium-90 in the dry state; correlations with phosphorus-32 Cherenkov counting data

We present data that illustrate some advantages of Cherenkov counting for the radioassay of ⁹⁰Y in the dry state and provide recommendations concerning sample counting geometry. Slightly higher detection efficiencies and figures-of-merit were obtained when counting ⁹⁰Y in the dry state in polyethylene plastic counting vials compared to the counting of ⁹⁰Y in 20 ml of water in borosilicate glass vials. The effects of polyethylene plastic counting vials and sample counting geometry are compared to similar data obtained in the Cherenkov counting of ³²P. Data are presented to interpret the effects of polyethylene plastic and borosilicate glass on Cherenkov counting efficiency and background counts. Applications of the Cherenkov counting of ⁹⁰Y and ³²P in the dry state in the biological and radiopharmaceutical sciences are foreseen as well as applications in the analysis of ⁹⁰Sr(⁹⁰Y) and ³²P in health physics and environmental monitoring.     

Clinical practice in radioembolization of hepatic malignancies: a survey among interventional centers in Europe

Objectives

A survey was conducted to give an overview about the practice of radioembolization in malignant liver tumors by European centers.

Methods

A questionnaire of 23 questions about the interventional center, preinterventional patient evaluation, the radioembolization procedure and aftercare were sent to 45 European centers.

Results

The response rate was 62.2% (28/45). The centers performed 1000 (median = 26) radioembolizations in 2009 and 1292 (median = 40) in 2010. Most centers perform preinterventional evaluation and radioembolization on an inpatient basis. An arterioportal shunt not amendable to preinterventional embolization is considered a contraindication. During preinterventional angiography, the gastroduodenal artery is embolized by 71%, the right gastric artery by 59%, and the cystic artery by 41%. In case of bilobar disease, yttrium-90 microspheres are infused into the common hepatic artery (14%) or separately into left and right hepatic artery (86%). 33% prefer a time interval between right and left liver lobe radioembolization to prevent radiation induced liver disease. 43% of the respondents do not prescribe prophylactic medication after radioembolization. In case of iatrogenic manipulation to the biliary duct system most centers perform radioembolization with prophylactic antibiotics.

Conclusions

Despite standardization of the procedure, there are some differences in how radioembolization of liver tumors is performed in Europe.     

Mixed-ligand complexes of yttrium-90 dialkyldithiocarbamates with 1,10-phenanthroline as a possible agent for therapy of hepatocellular carcinoma

Yttrium-90 is a radioelement which has found wide use in targeted radionuclide therapy because of its attractive physical and chemical properties. Radioembolisation of hepatocellular carcinoma with radiolabelled Lipiodol is a method of choice. We have synthesised a series of alkyldithiocarbamate yttrium complexes, easily extracted into Lipiodol due to their high lipophilicity. Among the prepared series, a new radioconjugate, which is stable over an extended period of time, has been prepared, and could represent a potential treatment procedure for hepatocellular carcinoma.     

Radioembolization with yttrium-90 resin microspheres for neuroendocrine tumor liver metastases

PURPOSE

We aimed to evaluate the effectiveness and safety of radioembolization with yttrium-90 (⁹⁰Y) microspheres in cases with unresectable neuroendocrine tumor liver metastases (NETLMs).

METHODS

Thirty patients (mean age, 55 years) underwent resin-based ⁹⁰Y radioembolization for unresectable NETLM at a single institution between April 2008 and June 2013. Post-treatment tumor response was assessed by cross-sectional imaging using the Response Evaluation Criteria in Solid Tumors (RECIST). Prognostic variables that affected survival were determined.

RESULTS

The mean follow-up was 23.0±19.4 months and the median overall survival was 39 months (95% CI, 12.6–65.4 months), with one- and two-year survival rates of 71% and 45%, respectively. Imaging follow-up using RECIST at three-month intervals demonstrated partial response in 43%, complete remission in 3%, stable disease in 37%, and progressive disease in 17% of patients. Extent of tumor involvement was found to have a statistically significant influence on overall survival (P = 0.03). The existence of extrahepatic disease at the time of radioembolization, radiographic response, age, and primary neuroendocrine tumor site were not significant prognostic factors.

CONCLUSION

The current study demonstrates the effectiveness and safety of radioembolization for the treatment of unresectable NETLMs. We identified that the extent of tumor involvement has a significant effect on overall survival. The use of imaging methods reflecting metabolic activity or cellularity such as scintigraphy or diffusion-weighted MRI would be more appropriate, for the response evaluation of liver metastases after radioembolization.Neuroendocrine tumors (NETs) are a heterogenous group of slow-growing and hormon-releasing malignant tumors. Even though primary NETs originate from a number of locations, 40%–70% of all carcinoids arise in the small intestine and appendix (1, 2). The most common site for metastasis is the liver. Neuroendocrine tumor liver metastasis (NETLM) results in hormone-secretion-related symptoms leading to carcinoid syndrome, pressure on structures, or liver replacement (1–4). Patients with liver metastasis have a five-year survival rate of less than 20% (5). Over the years, improvements in local treatments yielded better control of the symptoms and survival rates, yet only 10% of the patients have limited illness and are eligible for surgery (6). Patient symptomatology and survival can be improved by transarterial treatments like embolization and chemoembolization (6). Limitations of these techniques include the short duration of the effects and the controversial approaches regarding the optimal timing and sequence of the procedures due to the variability of tumor progression (7, 8). Long-term survival benefit was not achieved with systemic chemotherapy (9–11) and treatment with somatostatin analogues is mostly associated with symptomatic relief; there is no clear knowledge of their effect on survival of patients who have carcinoid tumor and metastasis (12).Selective internal radiation therapy (SIRT) has been used to treat unresectable primary and secondary liver cancers for over a decade. Yttrium-90 (⁹⁰Y) is a pure high-energy β emitter with a mean tissue penetration of 2.5 mm. The radioactive microspheres prefer tumoral vascular distribution, so that normal liver tissue is relatively spared and high doses are directed to the tumoral tissue (13). Also, radioembolization-related acute and subacute toxicities are seemingly more tolerable than the ones related to other hepatic embolization procedures (14–16). In this study, we aimed to evaluate the effectiveness and safety of ⁹⁰Y microspheres in cases with unresectable NETLMs.