90Y-microsphere radioembolization has become a well-established treatment option for liver malignancies and is one of the first U.S. Food and Drug Administration-approved unsealed radionuclide brachytherapy devices to incorporate dosimetry-based treatment planning. Several different mathematical models are used to calculate the patient-specific prescribed activity of 90Y, namely, body surface area (SIR-Spheres only), MIRD single compartment, and MIRD dual compartment (partition). Under the auspices of the MIRDsoft initiative to develop community dosimetry software and tools, the body surface area, MIRD single-compartment, MIRD dual-compartment, and MIRD multicompartment models have been integrated into a MIRDy90 software worksheet. The worksheet was built in MS Excel to estimate and compare prescribed activities calculated via these respective models. The MIRDy90 software was validated against available tools for calculating 90Y prescribed activity. The results of MIRDy90 calculations were compared with those obtained from vendor and community-developed tools, and the calculations agreed well. The MIRDy90 worksheet was developed to provide a vetted tool to better evaluate patient-specific prescribed activities calculated via different models, as well as model influences with respect to varying input parameters. MIRDy90 allows users to interact and visualize the results of various parameter combinations. Variables, equations, and calculations are described in the MIRDy90 documentation and articulated in the MIRDy90 worksheet. The worksheet is distributed as a free tool to build expertise within the medical physics community and create a vetted standard for model and variable management.

OBJECTIVE: This study aimed to determine the absorbed doses in the tumoral-liver and non-tumoral liver of hepatocellular carcinoma (HCC) patients undergoing radioembolization with Yttrium-90 (90Y) resin microspheres, and compared with those derived from 99mTc-MAA using the partition model.
METHODS: A total of 42 HCC patients (28 males and 14 females, mean age 65 ± 11.51 years) who received 45 treatment sessions with 90Y-microspheres between 2016 and 2021 were included. Pre-treatment 99mTc-MAA and post-treatment 90Y-bremsstrahlung SPECT/CT were acquired for each patient. Semi-automated segmentation of regions of interest (ROIs) was performed using MIM Encore software to determine the tumor-liver ratio (TLR) encompassing the liver volume, tumoral-liver, and lungs, and verified by both nuclear medicine physician and interventional radiologist. A partition dosimetry model was used to estimate the administered activity of 90Y-microspheres and the absorbed doses to the tumoral-liver and non-tumoral liver. The student\'s paired t test and Bland-Altman plot were used for the statistical analysis.
RESULTS: The mean TLR values obtained from 99mTc-MAA SPECT/CT and 90Y-bremsstrahlung SPECT/CT were 4.78 ± 3.51 and 2.73 ± 1.18, respectively. The mean planning administered activity of 90Y-microspheres based on 99mTc-MAA SPECT/CT was 1.56 ± 0.80 GBq, while the implanted administered activity was 2.53 ± 1.23 GBq (p value < 0.001). The mean absorbed doses in the tumoral-liver estimated from 99mTc-MAA and 90Y-bremsstrahlung SPECT/CT were 127.44 ± 4.36 Gy and 135.98 ± 6.30 Gy, respectively. The corresponding mean absorbed doses in the non-tumoral liver were 34.61 ± 13.93 Gy and 55.04 ± 16.36 Gy.
CONCLUSIONS: This study provides evidence that the administered activity of 90Y-microspheres, as estimated from 90Y-bremsstrahlung SPECT/CT, was significantly higher than that estimated from 99mTc-MAA SPECT/CT resulted in increased absorbed doses in both the tumoral-liver and non-tumoral liver. However, 99mTc-MAA SPECT/CT remains a valuable planning tool for predicting the distribution of 90Y-microspheres in liver cancer treatment.

Our aim was to assess the role of positron emission computed tomography (PET/CT) with 18F-choline (18F-FCH) or 18F-fluorodeoxyglucose (18F-FDG) in hepatocellular carcinoma (HCC) submitted to 90Y-radioembolization (90Y-TARE). We retrospectively analyzed clinical records of 21 HCC patients submitted to PET/CT with 18F-fluorocholine (18F-FCH) or 18F-fluodeoxyglucose (18F-FDG) before and 8 weeks after 90Y-TARE. On pre-treatment PET/CT, 13 subjects (61.9%) were 18F-FCH-positive, while 8 (38.1%) resulted 18F-FCH-negative and 18F-FDG-positive. At 8-weeks post 90Y-TARE PET/CT, 13 subjects showed partial metabolic response and 8 resulted non-responders, with a higher response rate among 18F-FCH-positive with respect to 18F-FDG-positive patients (i.e., 76.9% vs. 37.5%, p = 0.46). Post-treatment PET/CT influenced patients’ clinical management in 10 cases (47.6%); in 8 subjects it provided indication for a second 90Y-TARE targeting metabolically active HCC remnant, while in 2 patients it led to a PET-guided radiotherapy on metastatic nodes. By Kaplan−Meier analysis, patients’ age (≤69 y) and post 90Y-TARE PET/CT’s impact on clinical management significantly correlated with overall survival (OS). In Cox multivariate analysis, PET/CT’s impact on clinical management remained the only predictor of patients’ OS (p < 0.001). In our real-world study, PET/CT with 18F-FCH or 18F-FDG influenced clinical management and affected the final outcome for HCC patients treated with 90Y-TARE.

There has been a significant increase in the use of 90Y-microspheres in treating liver malignancies. This increase could be seen over the last 30 y, and Food and Drug Administration approval of 2 products-Sirtex SIR-Spheres and Boston Scientific TheraSphere-has helped in the proliferation of these treatments. As the increase in use of both products rose at our institution, there was a need to determine whether there should be special considerations for patients who receive one product compared with patients who receive the other product. This determination was made by measuring exposure rates for several regions of the patient before and after implantation. An independent-samples t test analysis (ɑ = 0.05) was performed for 50 patients (25 TheraSphere and 25 SIR-Spheres) to determine whether the products behaved similarly to the extent that exposure to others was minimized and that as-low-as-reasonably-achievable principles were kept. The results showed that the products exhibited no significant differences in exposure rates, suggesting that no special considerations are needed for the procedure for one product compared with the other.

Primary liver tumours (i.e. hepatocellular carcinoma (HCC) or intrahepatic cholangiocarcinoma (ICC)) are among the most frequent cancers worldwide. However, only 10-20% of patients are amenable to curative treatment, such as resection or transplant. Liver metastases are most frequently caused by colorectal cancer, which accounts for the second most cancer-related deaths in Europe. In both primary and secondary tumours, radioembolization has been shown to be a safe and effective treatment option. The vast potential of personalized dosimetry has also been shown, resulting in markedly increased response rates and overall survival. In a rapidly evolving therapeutic landscape, the role of radioembolization will be subject to changes. Therefore, the decision for radioembolization should be taken by a multidisciplinary tumour board in accordance with the current clinical guidelines. The purpose of this procedure guideline is to assist the nuclear medicine physician in treating and managing patients undergoing radioembolization treatment. PREAMBLE: The European Association of Nuclear Medicine (EANM) is a professional non-profit medical association that facilitates communication worldwide among individuals pursuing clinical and research excellence in nuclear medicine. The EANM was founded in 1985. These guidelines are intended to assist practitioners in providing appropriate nuclear medicine care for patients. They are not inflexible rules or requirements of practice and are not intended, nor should they be used, to establish a legal standard of care. The ultimate judgment regarding the propriety of any specific procedure or course of action must be made by medical professionals taking into account the unique circumstances of each case. Thus, there is no implication that an approach differing from the guidelines, standing alone, is below the standard of care. To the contrary, a conscientious practitioner may responsibly adopt a course of action different from that set out in the guidelines when, in the reasonable judgment of the practitioner, such course of action is indicated by the condition of the patient, limitations of available resources or advances in knowledge or technology subsequent to publication of the guidelines. The practice of medicine involves not only the science but also the art of dealing with the prevention, diagnosis, alleviation and treatment of disease. The variety and complexity of human conditions make it impossible to always reach the most appropriate diagnosis or to predict with certainty a particular response to treatment. Therefore, it should be recognised that adherence to these guidelines will not ensure an accurate diagnosis or a successful outcome. All that should be expected is that the practitioner will follow a reasonable course of action based on current knowledge, available resources and the needs of the patient to deliver effective and safe medical care. The sole purpose of these guidelines is to assist practitioners in achieving this objective.

OBJECTIVE: The need to concentrate the anti-tumoral activity of 90Y only to the targeted tumor, while minimizing its off-target effects, led to the development of an innovative device (BAT-90) composed of a hydrogel matrix and 90Y microspheres.
METHODS: This in vivo randomized study was planned to assess the efficacy, safety, and biodistribution of BAT-90 in 46 rabbits implanted with a VX2 tumor. The effects of BAT-90 were compared to those of 90Y microspheres and the hydrogel matrix.
RESULTS: BAT-90 localized effectively the 90Y radiation in the injection site, minimizing dispersion of the microspheres in the target and distant organs of the treated animals.
CONCLUSIONS: BAT-90 can be administered as an adjuvant treatment to clear surgical margins from any potential minimal residual disease, or as an alternative to other loco-regional treatments for non-resectable tumors.

BACKGROUND: Prior radioembolization, a simulation using 99mTc-macroaggregated albumin as 90Y-microspheres surrogate is performed. Gamma scintigraphy images (planar, SPECT, or SPECT-CT) are acquired to evaluate intrahepatic 90Y-microspheres distribution and detect possible extrahepatic and lung shunting. These images may be used for pre-treatment dosimetry evaluation to calculate the 90Y activity that would get an optimal tumor response while sparing healthy tissues. Several dosimetry methods are available, but there is still no consensus on the best methodology to calculate absorbed doses. The goal of this study was to retrospectively evaluate the impact of using different dosimetry approaches on the resulting 90Y-radioembolization pre-treatment absorbed dose evaluation based on 99mTc-MAA images.
METHODS: Absorbed doses within volumes of interest resulting from partition model (PM) and 3D voxel dosimetry methods (3D-VDM) (dose-point kernel convolution and local deposition method) were evaluated. Additionally, a new \"Multi-tumor Partition Model\" (MTPM) was developed. The differences among dosimetry approaches were evaluated in terms of mean absorbed dose and dose volume histograms within the volumes of interest.
RESULTS: Differences in mean absorbed dose among dosimetry methods are higher in tumor volumes than in non-tumoral ones. The differences between MTPM and both 3D-VDM were substantially lower than those observed between PM and any 3D-VDM. A poor correlation and concordance were found between PM and the other studied dosimetry approaches. DVH obtained from either 3D-VDM are pretty similar in both healthy liver and individual tumors. Although no relevant global differences, in terms of absorbed dose in Gy, between both 3D-VDM were found, important voxel-by-voxel differences have been observed.
CONCLUSIONS: Significant differences among the studied dosimetry approaches for 90Y-radioembolization treatments exist. Differences do not yield a substantial impact in treatment planning for healthy tissue but they do for tumoral liver. An individual segmentation and evaluation of the tumors is essential. In patients with multiple tumors, the application of PM is not optimal and the 3D-VDM or the new MTPM are suggested instead. If a 3D-VDM method is not available, MTPM is the best option. Furthermore, both 3D-VDM approaches may be indistinctly used.

Liver is the predominant site of metastatization for neuroendocrine tumors (NETs). Up to 75% of patients affected by intestinal NETs present liver metastases at diagnosis. For hepatic NET, surgery represents the most effective approach but is often unfeasible due to the massive involvement of multifocal disease. In such cases, chemotherapy, peptide receptor radionuclide therapy and loco-regional treatments may represent alternative therapeutic options. In particular, radioembolization with 90Y-microspheres has been introduced as a novel technique for treating hepatic malignant lesions, combining the principles of embolization and radiation therapy. In order to evaluate the response to 90Y-radioembolization, standard radiologic criteria have been demonstrated to present several limitations. 18Fluoro-deoxyglucose (FDG) Positron Emission Tomography (PET) is routinely used for monitoring the response to therapy in oncology. Nevertheless, NETs often present low glycolytic activity thus the conventional 18FDG PET may not be adequate for these tumors. For many years, somatostatin receptor scintigraphy (SRS) with 111In-pentetreotide has been used for diagnosis and staging of NETs. More recently, three 68Ga-DOTA-compounds have been developed and introduced for the imaging of NETs with PET technology. The aim of the present paper was to review the existing literature concerning the application of different metabolic and molecular probes for the imaging evaluation of hepatic NETs following 90Y-RE.

We present a case of a 42-year-old male patient affected by unresectable, chemorefractory cholangiocarcinoma, with prior placement of biliary stent. Because of the absence of extrahepatic metastases, he was submitted to liver-direct therapy with 90Y-microspheres. 18F-fluorodeoxyglucose positron emission tomography-computed tomography (FDG PET-CT) performed before the procedure showed intense tracer uptake in the hepatic lesion and along the biliary stent. The patient underwent radioembolization with 90Y-resin spheres (1.1 GBq). 18F-FDG PET-CT, acquired 6 weeks after the procedure, showed no response of the hepatic lesion and the appearance of an area of markedly increased uptake extending through the inferior vena cava into the right atrium, confirmed as extensive tumor thrombus at the enhanced multislice CT subsequently performed. 18F-FDG PET-CT proved to be a useful imaging tool not only for the evaluation of metabolic response but also for the early detection of extrahepatic progression after 90Y-radioembolization.

The aim of this study was to quantitatively evaluate the ability of the body-surface-area (BSA) model to predict tumor-absorbed dose and treatment outcome through retrospective voxel-based dosimetry. Methods: Data from 35 hepatocellular carcinoma patients with a total of 42 90Y-resin microsphere radioembolization treatments were included. Injected activity was planned with the BSA model. Voxel dosimetry based on 99mTc-labeled macroaggregated albumin SPECT and 90Y-microsphere PET was retrospectively performed using a dedicated treatment planning system. Average dose and dose-volume histograms (DVHs) of the anatomically defined tumors were analyzed. The selected dose metrics extracted from DVHs were minimum dose to 50% and 70% of the tumor volume and percentage of the volume receiving at least 120 Gy. Treatment response was evaluated 6 mo after therapy according to the criteria of the European Association for the Study of the Liver. Results: Six-month response was evaluated in 26 treatments: 14 were considered to produce an objective response and 12 a nonresponse. Retrospective evaluation of 90Y-microsphere PET-based dosimetry showed a large interpatient variability with a median average absorbed dose of 60 Gy to the tumor. In 62% (26/42) of the cases, tumor, nontumoral liver, and lung doses would have complied with the recommended thresholds if the injected activity calculated by the BSA method had been increased. Average doses, minimum dose to 50% and 70% of the tumor volume, and percentage of the volume receiving at least 120 Gy were significantly higher in cases of objective response than in nonresponse. Conclusion: In our population, average tumor-absorbed dose and DVH metrics were associated with tumor response. However, the activity calculated by the BSA method could have been increased to reach the recommended tumor dose threshold. Tumor uptake, target and nontarget volumes, and dose distribution heterogeneity should be considered for activity planning.