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A new 90Y SIR-Spheres delivery kit (SIROS D-vial and shield) has been introduced with a different physical form from the legacy V-Vial kit. Here, we establish the dose calibrator settings and exposure-rate-to-activity conversion factor to assay 90Y SIR-Spheres activity in the new SIROS kit. Methods: Eight D-vials with initial 90Y activities from 1.2 to 6.6 GBq within acrylic shields were assayed with dose calibrators and exposure-rate meters until activities decayed to approximately 0.1 GBq. The dose calibrator settings resulting in the lowest median activity errors and the best-fit slope of exposure rate versus activity were identified. Results: SIROS D-vial 90Y activity can be accurately and reliably estimated directly using setting 51 × 10 on both the CRC-15R and the CRC-55tR dose calibrators (errors within ±0.5%) and indirectly with an exposure-rate reading at 30 cm using conversion factor 0.664 ± 0.003 GBq/(mR/h) (R 2 = 0.985). Conclusion: Dose calibrator settings and exposure-rate-to-activity conversion factor for 90Y activity assays with new SIROS kit should be updated from legacy V-Vial parameters to avoid an approximately 10% underestimation.

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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.

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PURPOSE: 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. CONCLUSION: 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.

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Objetivo Para conocer los resultados de la radioembolización (transarterial radioembolization o TARE), en el tratamiento de tumores hepáticos, se realizó una valoración retrospectiva tras 112 TARE con 90Y-microesferas administradas en 82 pacientes en un único hospital, analizando la eficacia y la seguridad, tras un seguimiento mayor o igual a 1 año post-TARE en todos los pacientes, y evaluando la posible relación entre la respuesta al tratamiento y la supervivencia de los pacientes. Material y métodos Se administraron 57 TARE únicas y 55 TARE múltiples en pacientes con hepatocarcinoma (53), metástasis hepáticas (25) y colangiocarcinoma (4), con evaluación previa multidisciplinar clínica, angiográfica y gammagráfica (planar/SPECT/SPECT-TC con 99mTc-MAA), modelo multicompartimental (ecuaciones MIRD), valoración gammagráfica post-TARE (planar/SPECT/SPECT-TC), seguimiento clínico-radiológico, evaluación de respuesta tumoral (criterios mRECIST) y análisis (Kaplan Meier) de supervivencia libre de progresión (SLP) y supervivencia global (SG). Resultados La intención terapéutica fue paliativa (82%) y como puente a trasplante hepático/resección quirúrgica (17%). Se obtuvo respuesta (R), completa o parcial, en el 65,9% de los casos. Al año post-TARE estaban libres de progresión el 34,7% de los pacientes con R y 19,2% de los no R (p:0,003), con SG del 80% para los R y 37,5% para los no R (p:0,001). Las curvas de supervivencia mostraron mediana de SG de 18 meses (95% IC 15,7-20,3) para los R y 9 meses (95% IC 6,1-11,8) para los no R (p:0,03). Efectos secundarios leves (27,6%) y severos (5,3%) resueltos, sin mayor incidencia tras TARE múltiple. Conclusiones La TARE con 90Y-microesferas en pacientes adecuadamente seleccionados con tumores hepáticos, aporta eficacia terapéutica y bajo índice de toxicidad, con SLP y SG superiores en los pacientes con respuesta a la TARE respecto a los que no respondieron (AU)

Aim To determine the results of radioembolization transarterial (TARE), in the treatment of liver tumors, a retrospective evaluation was performed after 112 TARE with 90Y-microspheres administered in 82 patients in a single hospital, analyzing efficacy and safety, after a follow-up greater than or equal to 1 year post-TARE in all patients, and evaluating the possible relationship between treatment response and patient survival Material and methods We have administered 57 single TARE and 55 multiple TARE in patients with hepatocellular carcinoma (53), liver metastases (25) and cholangiocarcinoma (4), with prior multidisciplinary evaluation, clinical, angiographic and gammagraphic (planar/SPECT/SPECT-CT with 99mTc-MAA), multicompartment model (MIRD equations), post-TARE screening (planar/SPECT/SPECT-CT), clinical and radiological follow-up, tumor response evaluation (mRECIST criteria) and Kaplan–Meier analysis to determine progression-free survival (PFS) and overall survival (OS). Results Therapeutic intention was palliative (82%) and as bridge to liver transplantation/surgical resection (17%). We obtained response (R), complete or partial, in 65.9% of cases. One year after TARE 34.7% of patients with R and 19.2% of non-R were progression-free (p: 0.003), with OS of 80% for R and 37.5% for non-R (p: 0.001). Survival analysis showed median OS of 18 months (95% CI 15.7–20.3) for R and 9 months (95% CI 6.1–11.8) for non-R (p: 0.03). We found mild (27.6%) and severe (5.3%) side effects, all of them resolved, without higher incidence after multiple TARE. Conclusion TARE with 90Y-microspheres, in appropriately selected patients with liver tumors, provides therapeutic efficacy and low rate of toxicity, with higher PFS and OS in patients with TARE response compared to those who did not respond (AU)

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AIM: To determine the results of radioembolization transarterial (TARE), in the treatment of liver tumors, a retrospective evaluation was performed after 112 TARE with 90Y-microspheres administered in 82 patients in a single hospital, analyzing efficacy and safety, after a follow-up greater than or equal to 1 year post-TARE in all patients, and evaluating the possible relationship between treatment response and patient survival. MATERIAL AND METHODS: We have administered 57 single TARE and 55 multiple TARE in patients with hepatocellular carcinoma (53), liver metastases (25) and cholangiocarcinoma (4), with prior multidisciplinary evaluation, clinical, angiographic and gammagraphic (planar/SPECT/SPECT-CT with 99mTc-MAA), multicompartment model (MIRD equations), post-TARE screening (planar/SPECT/SPECT-CT), clinical and radiological follow-up, tumor response evaluation (mRECIST criteria) and Kaplan-Meier analysis to determine progression-free survival (PFS) and overall survival (OS). RESULTS: Therapeutic intention was palliative (82%) and as bridge to liver transplantation/surgical resection (17%). We obtained response (R), complete or partial, in 65.9% of cases. One year after TARE 34.7% of patients with R and 19.2% of non-R were progression-free (P: .003), with OS of 80% for R and 37.5% for non-R (P: .001). Survival analysis showed median OS of 18 months (95% CI 15.7-20.3) for R and 9 months (95% CI 6.1-11.8) for non-R (P: .03). We found mild (27.6%) and severe (5.3%) side effects, all of them resolved, without higher incidence after multiple TARE. CONCLUSION: TARE with 90Y-microspheres, in appropriately selected patients with liver tumors, provides therapeutic efficacy and low rate of toxicity, with higher PFS and OS in patients with TARE response compared to those who did not respond.

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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.

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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.

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Yttrium-90 (90Y) microspheres are widely used for the treatment of liver-dominant malignant tumors. They are infused via catheter into the hepatic artery branches supplying the tumor under fluoroscopic guidance based on pre-therapy angiography and Technetium-99m macroaggregated albumin (99mTc-MAA) planning. However, at present, these microspheres are suspended in radiolucent media such as dextrose 5% (D5) solution. In order to monitor the real-time implantation of the microspheres into the tumor, the 90Y microspheres could be suspended in omnipaque contrast for allowing visualization of the correct distribution of the microspheres into the tumor. The radiochemical purity of mixing 90Y-microspheres in various concentrations of omnipaque was investigated. The radiochemical purity and feasibility of mixing 99mTc-MAA with various concentrations of a standard contrast agent were also investigated. Results showed the radiochemical feasibility of mixing 90Y-microspheres with omnipaque is radiochemically acceptable for allowing real-time visualization of radioembolization under fluoroscopy.

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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.

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BACKGROUND/AIM: 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. MATERIALS AND 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. CONCLUSION: 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.

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The aim of this standard operational procedure is to standardize the methodology employed for the evaluation of pre- and post-treatment absorbed dose calculations in 90Y microsphere liver radioembolization. Basic assumptions include the permanent trapping of microspheres, the local energy deposition method for voxel dosimetry, and the patient-relative calibration method for activity quantification.The identity of 99mTc albumin macro-aggregates (MAA) and 90Y microsphere biodistribution is also assumed. The large observed discrepancies in some patients between 99mTc-MAA predictions and actual 90Y microsphere distributions for lesions is discussed. Absorbed dose predictions to whole non-tumoural liver are considered more reliable and the basic predictors of toxicity. Treatment planning based on mean absorbed dose delivered to the whole non-tumoural liver is advised, except in super-selective treatments.Given the potential mismatch between MAA simulation and actual therapy, absorbed doses should be calculated both pre- and post-therapy. Distinct evaluation between target tumours and non-tumoural tissue, including lungs in cases of lung shunt, are vital for proper optimization of therapy. Dosimetry should be performed first according to a mean absorbed dose approach, with an optional, but important, voxel level evaluation. Fully corrected 99mTc-MAA Single Photon Emission Computed Tomography (SPECT)/computed tomography (CT) and 90Y TOF PET/CT are regarded as optimal acquisition methodologies, but, for institutes where SPECT/CT is not available, non-attenuation corrected 99mTc-MAA SPECT may be used. This offers better planning quality than non dosimetric methods such as Body Surface Area (BSA) or mono-compartmental dosimetry. Quantitative 90Y bremsstrahlung SPECT can be used if dedicated correction methods are available.The proposed methodology is feasible with standard camera software and a spreadsheet. Available commercial or free software can help facilitate the process and improve calculation time.

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PURPOSE: To investigate the potential of texture analysis and machine learning to predict treatment response to transarterial radioembolization (TARE) on pre-interventional cone-beam computed tomography (CBCT) images in patients with liver metastases. MATERIALS AND METHODS: In this IRB-approved retrospective single-center study 36 patients with a total of 104 liver metastases (56 % male, mean age 61.1 ± 13 years) underwent CBCT prior to TARE and follow-up imaging 6 months after therapy. Treatment response was evaluated according to RECIST version 1.1 and dichotomized into disease control (partial response/stable disease) versus disease progression (progressive disease). After target lesion segmentation, 104 radiomics features corresponding to seven different feature classes were extracted with the pyRadiomics package. After dimension reduction machine learning classifications were performed on a custom artificial neural network (ANN). Ten-fold cross validation on a previously unseen test data set was performed. RESULTS: The average administered cumulative activity from TARE was 1.6 Gbq (± 0.5 Gbq). At a mean follow-up of 5.9 ± 0.8 months disease control was achieved in 82 % of metastases. After dimension reduction, 15 of 104 (15 %) texture analysis features remained for further analysis. On a previously unseen set of liver metastases the Multilayer Perceptron ANN yielded a sensitivity of 94.2 %, specificity of 67.7 % and an area-under-the receiver operating characteristics curve of 0.85. CONCLUSION: Our study indicates that texture analysis-based machine learning may has potential to predict treatment response to TARE using pre-treatment CBCT images of patients with liver metastases with high accuracy.

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INTRODUCTION AND OBJECTIVE: Neuroendocrine tumors (NETs) debut in 75% of cases with liver metastases (LMNETs), whose therapeutic approach includes surgical resection and liver transplantation, while liver radioembolization with 90 Y-microspheres (TARE) is reserved for non-operable patients usually due to high tumor burden. We present the accumulated experience of 10 years in TARE treatment of LMNETs in order to describe the safety and the effectiveness of the oncological response in terms of survival, as well as to detect the prognostic factors involved. MATERIAL AND METHODS: Of 136 TARE procedures, performed between January 2006 and December 2016, 30 LMNETs (11.1%) were retrospectively analyzed. The study variables were: Tumor response, time to liver progression, survival at 3 and 5 years, overall mortality and mortality associated with TARE. The radiological response assessment was assessed using RECIST 1.1 and mRECIST criteria. RESULTS: An average activity of 2.4 ± 1.3 GBq of 90 Y was administered. No patient presented postembolization syndrome or carcinoid syndrome. There were also no vascular complications associated with the procedure. According to RECIST 1.1 criteria at 6 months, 78.6% presented partial response and 21.4% stable disease, there was no progression or complete response (1 by mRECIST). Survival at 3 and 5 years was 73% in both cases. CONCLUSION: TARE treatment with 90 Y-microspheres in LMNETs, applied within a multidisciplinary approach, is a safe procedure, with low morbidity, capable of achieving a high rate of radiological response and achieving lasting tumor responses.

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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.

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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.

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The aim of this work was to develop models for tumor control probability (TCP) in radioembolization with 90Y PET/CT-derived radiobiologic dose metrics. Methods: Patients with primary liver cancer or liver metastases who underwent radioembolization with glass microspheres were imaged with 90Y PET/CT for voxel-level dosimetry to determine lesion absorbed dose (AD) metrics, biological effective dose (BED) metrics, equivalent uniform dose, and equivalent uniform BED for 28 treatments (89 lesions). The lesion dose-shrinkage correlation was assessed on the basis of RECIST and, when available, modified RECIST (mRECIST) at first follow-up. For a subset with mRECIST, logit regression TCP models were fit via maximum likelihood to relate lesion-level binary response to the dose metrics. As an exploratory analysis, the nontumoral liver dose-toxicity relationship was also evaluated. Results: Lesion dose-shrinkage analysis showed that there were no significant differences between model parameters for primary and metastatic subgroups and that correlation coefficients were superior with mRECIST. Therefore, subsequent TCP analysis was performed for the combined group using mRECIST only. The overall lesion-level mRECIST response rate was 57%. The AD and BED metrics yielding 50% TCP were 292 and 441 Gy, respectively. All dose metrics considered for TCP modeling, including mean AD, were significantly associated with the probability of response, with high areas under the curve (0.87-0.90, P < 0.0001) and high sensitivity (>0.75) and specificity (>0.83) calculated using a threshold corresponding to 50% TCP. Because nonuniform AD deposition by microspheres cannot be determined by PET at a microscopic scale, radiosensitivity values extracted here by fitting models to clinical response data were substantially lower than reported for in vitro cell cultures or for external-beam radiotherapy clinical studies. There was no correlation between nontumoral liver AD and toxicity measures. Conclusion: Despite the heterogeneous patient cohort, logistic regression TCP models showed a strong association between various dose metrics and the probability of response. The performance of mean AD was comparable to that of radiobiologic dose metrics that involve more complex calculations. These results demonstrate the importance of considering TCP in treatment planning for radioembolization.

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PURPOSE: There are several important positron emission tomography (PET) imaging scenarios that require imaging with very low photon statistics, for which both quantitative accuracy and visual quality should not be neglected. For example, PET imaging with the low photon statistics is closely related to active efforts to significantly reduce radiation exposure from radiopharmaceuticals. We investigated two examples of low-count PET imaging: (a) imaging [90Y]microsphere radioembolization that suffers the very small positron emission fraction of Y-90's decay processes, and (b) cancer imaging with [68Ga]citrate with uptake time of 3-4 half-lives, necessary for visualizing tumors. In particular, we investigated a type of penalized likelihood reconstruction algorithm, block sequential regularized expectation maximization (BSREM), for improving both image quality and quantitative accuracy of these low-count PET imaging cases. PROCEDURES: The NEMA/IEC Body phantom filled with aqueous solution of Y-90 or Ga-68 was scanned to mimic the low-count scenarios of corresponding patient data acquisitions on a time-of-flight (TOF) PET/magnetic resonance imaging system. Contrast recovery, background variation, and signal-to-noise ratio were evaluated in different sets of count densities using both conventional TOF ordered subset expectation (TOF-OSEM) and TOF-BSREM algorithms. The regularization parameter, beta, in BSREM that controls the tradeoff between image noise and resolution was evaluated to find a value for improved confidence in image interpretation. Visual quality assessment of the images obtained from patients administered with [68Ga]citrate (n = 6) was performed. We also made preliminary visual image quality assessment for one patient with [90Y]microspheres. In Y-90 imaging, the effect of 511-keV energy window selection for minimizing the number of random events was also evaluated. RESULTS: Quantitatively, phantom images reconstructed with TOF-BSREM showed improved contrast recovery, background variation, and signal-to-noise ratio values over images reconstructed with TOF-OSEM. Both phantom and patient studies of delayed imaging of [68Ga]citrate show that TOF-BSREM with beta = 500 gives the best tradeoff between image noise and image resolution based on visual assessment by the readers. The NEMA-IQ phantom study with [90Y]microspheres shows that the narrow energy window (460-562 keV) recovers activity concentrations in small spheres better than the regular energy window (425-650 keV) with the beta value of 2000 using the TOF-BSREM algorithm. For the images obtained from patients with [68Ga]citrate using TOF-BSREM with beta = 500, the visual analogue scale (VAS) was improved by 17 % and the Likert score was increased by 1 point on average, both in comparison to corresponding scores for images reconstructed using TOF-OSEM. CONCLUSION: Our investigation shows that the TOF-BSREM algorithm improves the image quality and quantitative accuracy in low-count PET imaging scenarios. However, the beta value in this algorithm needed to be adjusted for each radiopharmaceutical and counting statistics at the time of scans.

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The aim of our study was to compare dosimetry methods for yttrium-90 (90Y) positron emission tomography/computed tomography (PET/CT). Twenty-five patients were taken to a PET/CT suite following therapy with 90Y microspheres. The low mA, nondiagnostic CT images were used for attenuation correction and localization of the 90Y microspheres. The acquisition time was 15 min, the reconstruction matrix size was 200 mm × 200 mm × 75 mm, and voxel size was 4.07 mm × 4.07 mm × 3.00 mm. Two software packages, MIM 6.8 and Planet Dose, were utilized to calculate 90Y dosimetry. Three methods were used for voxel-based dosimetry calculations: the local deposition method (LDM), LDM with scaling (LDMwS) for known injected activity, and a dose point kernel (DPK) method using the MIRD kernel. Only the DPK approach was applied to the Planet Dose software. LDM and LDMwS were only applied to the MIM software. The average total liver dosimetry values (mean ± standard deviation) were 60.93 ± 28.62 Gy, 53.59 ± 23.47 Gy, 55.33 ± 24.80 Gy, and 54.25 ± 23.70 Gy for LDMwS, LDM, DPK with MIM, and DPK with Planet Dose (DOSI), respectively. In most cases, the LDMwS method produced slightly higher dosimetry values than the other methods. The MIM and Planet Dose DPK dosimetry values (i.e., DPK vs. DOSI) were highly comparable. Bland-Altman analysis calculated a mean difference of 1.1 ± 2.2 Gy. The repeatability coefficient was 4.4 (7.9% of the mean). The MIM and Planet Dose DPK dosimetry values were practically interchangeable. 90Y dosimetry values obtained by all methods were similar, but LDMwS tended to produce slightly higher values.

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Pretreatment dual-tracer (18F-fluorodeoxyglucose and 11C-acetate) PET/computed tomography (CT) has potential to predict treatment response for 90Y microsphere radioembolization (RE) in patients with inoperable hepatocellular carcinoma (HCC). Patients with 11C-acetate-avid HCC have a better response to 90Y microsphere RE, and possibly better survival. Pretreatment dual-tracer PET/CT has a significant theranostic value on 90Y microsphere RE in determining target tumor dose for HCCs with different cellular differentiation, metabolic tumor volume, and functioning liver volume, and can be used to prescribe individual injected activity of 90Y microspheres.

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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.