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Purpose: Pre-treatment [ 99m Tc]TcMAA-based radioembolization treatment planning using multicompartment dosimetry involves the definition of the tumor and normal tissue compartments and calculation of the prescribed absorbed doses. The aim was to compare the real-world utility of anatomic and [ 99m Tc]TcMAA-based segmentation of tumor and normal tissue compartments., Materials and Methods: Included patients had HCC treated by glass [ 90 Y]yttrium microspheres, ≥ 1 tumor, ≥ 3 cm diameter and [ 99m Tc]TcMAA SPECT/CT imaging before treatment. Segmentation was performed retrospectively using dedicated dosimetry software: (1) anatomic (diagnostic CT/MRI-based), and (2) [ 99m Tc]TcMAA threshold-based (i.e., using an activity-isocontour threshold). CT/MRI was co-registered with [ 99m Tc]TcMAA SPECT/CT. Logistic regression and Cox regression, respectively, were used to evaluate relationships between total perfused tumor absorbed dose (TAD) and objective response rate (ORR) and overall survival (OS). In a subset-analysis pre- and post-treatment dosimetry were compared using Bland-Altman analysis and Pearson's correlation coefficient., Results: A total of 209 patients were enrolled. Total perfused tumor and normal tissue volumes were larger when using anatomic versus [ 99m Tc]TcMAA threshold segmentation, resulting in lower absorbed doses. mRECIST ORR was higher with increasing total perfused TAD (odds ratio per 100 Gy TAD increase was 1.22 (95% CI: 1.01-1.49; p = 0.044) for anatomic and 1.19 (95% CI: 1.04-1.37; p = 0.012) for [ 99m Tc]TcMAA threshold segmentation. Higher total perfused TAD was associated with improved OS (hazard ratio per 100 Gy TAD increase was 0.826 (95% CI: 0.714-0.954; p = 0.009) and 0.847 (95% CI: 0.765-0.936; p = 0.001) for anatomic and [ 99m Tc]TcMAA threshold segmentation, respectively). For pre- vs. post-treatment dosimetry comparison, the average bias for total perfused TAD was + 11.5 Gy (95% limits of agreement: -227.0 to 250.0) with a strong positive correlation (Pearson's correlation coefficient = 0.80)., Conclusion: Real-world data support [ 99m Tc]TcMAA imaging to estimate absorbed doses prior to treatment of HCC with glass [ 90 Y]yttrium microspheres. Both anatomic and [ 99m Tc]TcMAA threshold methods were suitable for treatment planning., Trial Registration Number: NCT03295006., Competing Interests: Declarations. Conflicts of Interest/Competing interests: Marnix Lam, MD, PhD: Is a consultant for Boston Scientific, Terumo and Quirem Medical. He receives research support from Boston Scientific, Terumo and Quirem Medical. The UMC Utrecht receives royalties from Quirem Medical. Etienne Garin, MD, PhD: Serves as a consultant for Boston Scientific. Paul Haste, MD: Is a consultant for Boston Scientific. Alban Denys, MD, MSc: Is a consultant for Cook, Neuwave, and received grants from Johnson and Johnson. Brian Geller, MD: Nothing to disclose. S. Cheenu Kappadath, PhD: Is a consultant for Boston Scientific, Sirtex Medical, and Terumo Medical. He receives research support from Boston Scientific, Sirtex Medical and ABK Biomedical. Cuneyt Turkmen, MD: Is a consultant for Boston Scientific. Daniel Y Sze, MD, PhD: Was a consultant for Argon, Artio Medical, Astra-Zeneca, Bayer, BlackSwan Vascular, Boston Scientific, Bristol Meyers Squibb, Eisai, FludX, W.L. Gore, Guerbet, Koli, Sirtex, Terumo, TriSalus, and Varian; received institutional research support from Boston Scientific, W.L. Gore, Merit Medical, and Sirtex; held equity in BlackSwan Vascular, Confluent Medical, Koli, Proteus Digital Health, Radiaction, and TriSalus; and serves on data safety monitoring boards for W.L. Gore and Replimune. Hamad Saleh Alsuhaibani, MD: Nothing to disclose. Ken Herrmann, MD: Reports personal fees from Bayer, personal fees and other from Sofie Bioscienes, personal fees from SIRTEX, non-financial support from ABX, personal fees from Adacap, personal fees from Curium, personal fees from Endocyte, grants and personal fees from Boston Scientific, personal fees from IPSEN, personal fees from Siemens Healthineers, personal fees from GE Healthcare, personal fees from Amgen, personal fees from Novartis, personal fees from ymabs, personal fees from Aktis Oncology, personal fees from Theragnostics, personal fees from Pharma15, outside the submitted work. Marco Maccauro, MD: Nothing to disclose. Murat Cantasdemir, MD: Is a consultant for Boston Scientific. Matthew Dreher, PhD: Works for Boston Scientific. Kirk D. Fowers, PhD: Works for Boston Scientific. Vanessa Gates, PhD: Is a consultant for Boston Scientific. Riad Salem, MD: Is a consultant for Boston Scientific, AstraZeneca, Genentech, Sirtex, Cook, Eisai, Bard and QED Therapeutics. Ethics approval: Not Applicable. Consent to participate: Not Applicable., (© 2024. The Author(s).)

Purpose: To determine 6-month interim safety, effectiveness, and multimodal imageability of imageable glass microsphere yttrium-90 ( 90 Y) radioembolization for unresectable hepatocellular carcinoma (HCC) in a first-in-human trial., Materials and Methods: Imageable microspheres (Eye90 Microspheres; ABK Biomedical, Halifax, Nova Scotia, Canada), a U.S. Food and Drug Administration (FDA) Breakthrough-Designated Device consisting of glass radiopaque 90 Y microspheres visible on computed tomography (CT) and single photon emission CT (SPECT), were used to treat 6 subjects with unresectable HCC. Patients underwent selective (≤2 segments) treatment in a prospective open-label pilot trial. Key inclusion criteria included liver-only HCC, performance status ≤1, total lesion diameter ≤9 cm, and Child-Pugh A status. Prospective partition dosimetry was utilized. Safety (measured by Common Terminology Criteria for Adverse Events [CTCAE] v5), multimodal imageability on CT and SPECT, and 3- and 6-month imaging response by modified Response Evaluation Criteria in Solid Tumors on magnetic resonance (MR) imaging were evaluated., Results: Seven tumors in 6 subjects were treated and followed to 180 days. Administration success was 100%. Microsphere distribution measured by radiopacity on CT correlated with SPECT. Ninety-day target lesion complete response (CR) was observed in 3 of 6 subjects (50%) and partial response (PR) in 2 (33.3%). At 180 days, target lesion CR was maintained in 3 subjects (50%) and PR in 1 (16.7%). Two subjects could not be reassessed, having undergone intervening chemoembolization. All subjects reported adverse events (AEs), and 5 reported AEs related to treatment. There were no treatment-related Grade ≥3 AEs., Conclusions: Radioembolization using imageable microspheres was safe and effective in 6 subjects with unresectable HCC at 6-month interim analysis. Microsphere distribution by radiopacity on CT correlated with radioactivity distribution by SPECT, providing previously unavailable CT-based tumor targeting information., (Copyright © 2024 SIR. Published by Elsevier Inc. All rights reserved.)

A new 90 Y 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 90 Y SIR-Spheres activity in the new SIROS kit. Methods: Eight D-vials with initial 90 Y 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 90 Y 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 90 Y activity assays with new SIROS kit should be updated from legacy V-Vial parameters to avoid an approximately 10% underestimation., (© 2024 by the Society of Nuclear Medicine and Molecular Imaging.)

Background: Personalized dosimetry improves overall survival (OS) in patients with hepatocellular carcinoma (HCC) treated with glass 90 Y radioembolization. This study evaluated personalized tumor dose (TD) as a predictor of OS, progression-free survival (PFS), and local duration of response (DOR) in patients with surgically unresectable HCC treated with resin 90 Y radioembolization., Patients and Methods: This prospective, single-center, single-arm clinical trial (NCT04172714) evaluated the efficacy of scout activity of resin 90 Y versus 99m Tc-MAA for treatment planning. A secondary aim of this study was to evaluate personalized dosimetry as a predictor of OS, PFS, and DOR. Partition dosimetry model was utilized for nonsegmental therapies with targeted TD >200 Gy and nontumoral liver dose <70 Gy. Single compartment dose of 200 Gy was used for segmentectomies. OS, PFS, and local DOR from 90 Y was estimated using Kaplan-Meier estimation with log-rank analysis used to determine predictors of prolonged survival., Findings: Thirty patients with treatment-naive HCC and 33 tumors (19 segmental and 14 nonsegmental) were included. Overall, 18 patients underwent segmental Y90-RE and 12 underwent non-segmental/lobar therapies. The mean 90 Y TD was 493 Gy. The median follow-up since enrollment into the study was 37 months. The mean OS was 32.2 months for the entire cohort. A total of 5 patients underwent orthotopic liver transplantation post 90 Y and were excluded from further survival analysis. The mean OS for the remainder of the cohort was 30.1 months (median not reached). The mean TD >250 Gy resulted in prolonged mean OS and PFS. The median local DOR was 32.7 months with mean TD 330 Gy predicting prolonged DOR., Interpretation: For patients with surgically unresectable HCC treated with resin 90 Y, there is mean TD threshold predicting prolonged OS, PFS, and local DOR. Therefore, there should be further emphasis on personalized dosimetry for optimization of patient outcomes., Competing Interests: Conflicts of interest and sources of funding: This study was jointly funded by Radiological Society of North America and Sirtex Medical Ltd. The study sponsors had no role in the design, data interpretation, or decision to publish this study. N.K. discloses he works as a consultant for Sirtex Medical Ltd. No other potential conflicts of interest relevant to this article exist., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Purpose: To report outcomes of yttrium-90 ( 90 Y) radioembolization in patients with unresectable intrahepatic cholangiocarcinoma (ICC)., Materials and Methods: Retrospective review was performed of 115 patients at 6 tertiary care centers; 92 were treated with resin microspheres (80%), 22 were treated with glass microspheres (19%), and 1 was treated with both. Postintervention outcomes were compared between groups with χ 2 tests. Survival after diagnosis and after treatment was assessed by Kaplan-Meier method., Results: Grade 3 laboratory toxicity was observed in 4 patients (4%); no difference in toxicity profile between resin and glass microspheres was observed (P = .350). Clinical toxicity per Society of Interventional Radiology criteria was noted in 29 patients (25%). Partial response per Response Evaluation Criteria In Solid Tumors 1.1 was noted in 25% of patients who underwent embolization with glass microspheres and 3% of patients who were treated with resin microspheres (P = .008). Median overall survival (OS) from first diagnosis was 29 months (95% confidence interval [CI], 21-37 mo) for all patients, and 1-, 3-, and 5-year OS rates were 85%, 31%, and 8%, respectively. Median OS after treatment was 11 months (95% CI, 8-13 mo), and 1- and 3-year OS rates were 44% and 4%, respectively. These estimates were not significantly different between resin and glass microspheres (P = .730 and P = .475, respectively). Five patients were able to undergo curative-intent resection after 90 Y radioembolization (4%)., Conclusions: This study provides observational data of treatment outcomes after 90 Y radioembolization in patients with unresectable ICC., (Copyright © 2020 SIR. Published by Elsevier Inc. All rights reserved.)

Purpose: Peptide receptor radionuclide therapy (PRRT) and radioembolization are increasingly used in neuroendocrine neoplasms patients. However, concerns have been raised on cumulative hepatotoxicity. The aim of this sub-analysis was to investigate hepatotoxicity of yttrium-90 resin microspheres radioembolization in patients who were previously treated with PRRT., Methods: Patients treated with radioembolization after systemic radionuclide treatment were retrospectively analysed. Imaging response according to response evaluation criteria in solid tumours (RECIST) v1.1 and clinical response after 3 months were collected. Clinical, biochemical and haematological toxicities according to common terminology criteria for adverse events (CTCAE) v4.03 were also collected. Specifics on prior PRRT, subsequent radioembolization treatments, treatments after radioembolization and overall survival (OS) were collected., Results: Forty-four patients were included, who underwent a total of 58 radioembolization procedures, of which 55% whole liver treatments, at a median of 353 days after prior PRRT. According to RECIST 1.1, an objective response rate of 16% and disease control rate of 91% were found after 3 months. Clinical response was seen in 65% (15/23) of symptomatic patients after 3 months. Within 3 months, clinical toxicities occurred in 26%. Biochemical and haematological toxicities CTCAE grade 3-4 occurred in ≤ 10%, apart from lymphocytopenia (42%). Radioembolization-related complications occurred in 5% and fatal radioembolization-induced liver disease in 2% (one patient). A median OS of 3.5 years [95% confidence interval 1.8-5.1 years] after radioembolization for the entire study population was found., Conclusion: Radioembolization after systemic radionuclide treatments is safe, and the occurrence of radioembolization-induced liver disease is rare., Level of Evidence: 4, case series.

Purpose: Current treatment planning for 90 Y radioembolization estimates lung mean dose (LMD) by measuring the lung shunt fraction (LSF) from 99m Tc-macroaggregated albumin (MAA) planar imaging and assuming a 1-kg lung mass. This methodology, however, overestimates LSF and LMD and could therefore unnecessarily limit the dose to target volume(s). We propose an improved LMD calculation that derives LSF from 99m Tc-MAA SPECT/CT and the patient-specific lung mass from diagnostic chest CT. Furthermore, we investigated the errors in lung mass, LSF, and LMD arising from contour variability in patient data in order to estimate the precision of our proposed methodology., Methods: Our proposed LMD (LMD new ) calculation consisted of the following steps: (a) estimate liver counts from the MAA SPECT/CT liver contour; (b) estimate total lung counts by multiplying density (counts/g) from the MAA SPECT/CT left-lung contour by the total lung mass (g) from the diagnostic CT lung contours; (c) compute LSF new from liver and lung counts; (d) calculate LMD new using LSF new and the total lung mass from the diagnostic CT (M new ). LMD new , LSF new , and M new estimates were compared to standard model values (LMD clin , LSF clin , and 1 kg, respectively) in 52 consecutive patients with hepatocellular carcinoma who underwent radioembolization using 90 Y glass microspheres. The precision of our methodology was quantified by varying lung and liver contours in the same patient population and calculating the resulting relative errors in the liver count, lung count, and lung mass measurements., Results: The median M new was 839 g (range, 550-1178 g) for men and 731 g (range, 548-869 g) for women. The median LSF new was 0.02 (range, 0.01-0.11), while the median LMD new was 4.9 Gy (range, 0.3-25.5 Gy). M new , LSF new , and LMD new were significantly lower than M clin , LSF clin , and LMD clin , with respective relative mean (±SD) differences of -20% (±16%) for M new , -63% (±15%) for LSF new , and -53% (±23%) for LMD new . The estimated 1-sigma uncertainties in M new , LSF new , and LMD new were 9%, 10%, and 13%, respectively., Conclusions: We derived a method to calculate lung mass and LSF using routinely available diagnostic chest CT and 99m Tc-MAA SPECT/CT. More importantly, we systematically quantified the errors in our measurements to establish the precision of the estimated lung dose (13%). The proposed methodology provides a more accurate LMD and an estimate of its precision, which will improve treatment and retreatment planning for 90 Y radioembolizations., (© 2019 American Association of Physicists in Medicine.)

The TheraSphere Global Dosimetry Steering Committee was formed in 2017 by BTG International to review existing data and address gaps in knowledge related to dosimetry. This committee is comprised of health care providers with diverse areas of expertise and perspectives on radiation dosimetry. The goal of these recommendations is to optimize glass microspheres radiation therapy for hepatocellular carcinoma while accounting for variables including disease presentation, tumour vascularity, liver function, and curative/palliative intent. The recommendations aim to unify glass microsphere users behind standardized dosimetry methodology that is simple, reproducible and supported by clinical data, with the overarching goal of improving clinical outcomes and advancing the knowledge of dosimetry.

Purpose: Radioembolization of liver metastases of neuroendocrine neoplasms (NEN) has shown promising results; however, the current literature is of limited quality. A large international, multicentre retrospective study was designed to address several shortcomings of the current literature., Materials: 244 NEN patients with different NEN grades were included., Methods: Primary outcome parameters were radiologic response 3 and 6 months after treatment according to RECIST 1.1 and mRECIST. Secondary outcome parameters included clinical response, clinical and biochemical toxicities., Results: Radioembolization resulted in CR in 2%, PR in 14%, SD in 75% and PD 9% according to RECIST 1.1 and in CR in 8%, PR in 35%, SD in 48% and PD in 9% according to mRECIST. Objective response rates improved over time in 20% and 26% according to RECIST 1.1. and mRECIST, respectively. Most common new grade 3-4 biochemical toxicity was lymphocytopenia (6.7%). No unexpected clinical toxicities occurred. Radioembolization-specific complications occurred in < 4%. In symptomatic patients, improvement and resolution of symptoms occurred in 44% and 34%, respectively. Median overall survival from first radioembolization was 3.7, 2.7 and 0.7 years for G1, G2 and G3, respectively. Objective response is independent of NEN grade or primary tumour origin. Significant prognostic factors for survival were NEN grade/Ki67 index, ≥ 75% intrahepatic tumour load, the presence of extrahepatic disease and disease control rate according to RECIST 1.1., Conclusion: Safety and efficacy of radioembolization in NEN patients was confirmed with a high disease control rate of 91% in progressive patients and alleviation of NEN-related symptoms in 79% of symptomatic patients., Level of Evidence: 4.

Purpose: 90 Y-microsphere radioembolization or selective internal radiation therapy is increasingly being used as a treatment option for tumors that are not candidates for surgery and external beam radiation therapy. Recently, volumetric 90 Y-dosimetry techniques have been implemented to explore tumor dose-response on the basis of 3D 90 Y-activity distribution from PET imaging. Despite being a theranostic study, the optimization of quantitative 90 Y-PET image reconstruction still uses the mean activity concentration recovery coefficient (RC) as the objective function, which is more relevant to diagnostic and detection tasks than is to dosimetry. The aim of this study was to optimize 90 Y-PET image reconstruction by minimizing errors in volumetric dosimetry via the dose volume histogram (DVH). We propose a joint optimization of the number of equivalent iterations (the product of the iterations and subsets) and the postreconstruction filtration (FWHM) to improve the accuracy of voxel-level 90 Y dosimetry., Methods: A modified NEMA IEC phantom was used to emulate clinically relevant 90 Y-PET imaging conditions through various combinations of acquisition durations, activity concentrations, sphere-to-background ratios, and sphere diameters. PET data were acquired in list mode for 300 min in a single-bed position; we then rebinned the list mode PET data to 60, 45, 30, 15, and 5 min per bed, with 10 different realizations. Errors in the DVH were calculated as root mean square errors (RMSE) of the differences in the image-based DVH and the expected DVH. The new optimization approach was tested in a phantom study, and the results were compared with the more commonly used objective function of the mean activity concentration RC., Results: In a wide range of clinically relevant imaging conditions, using 36 equivalent iterations with a 5.2-mm filtration resulted in decreased systematic errors in volumetric 90 Y dosimetry, quantified as image-based DVH, in 90 Y-PET images reconstructed using the ordered subset expectation maximization (OSEM) iterative reconstruction algorithm with time of flight (TOF) and point spread function (PSF) modeling. Our proposed objective function of minimizing errors in DVH, which allows for joint optimization of 90 Y-PET iterations and filtration for volumetric quantification of the 90 Y dose, was shown to be superior to conventional RC-based optimization approaches for image-based absorbed dose quantification., Conclusion: Our proposed objective function of minimizing errors in DVH, which allows for joint optimization of iterations and filtration to reduce errors in the PET-based volumetric quantification 90 Y dose, is relevant to dosimetry in therapy procedures. The proposed optimization method using DVH as the objective function could be applied to any imaging modality used to assess voxel-level quantitative information., (© 2018 American Association of Physicists in Medicine.)

Purpose: To investigate hepatocellular carcinoma tumor dose-response characteristics based on voxel-level absorbed doses (D) and biological effective doses (BED) using quantitative 90 Y-single-photon emission computed tomography (SPECT)/computed tomography (CT) after 90 Y-radioembilization with glass microspheres. We also investigated the relationship between normal liver D and toxicities., Methods and Materials: 90 Y-radioembolization activity distributions for 34 patients were based on quantitative 90 Y-bremsstrahlung SPECT/CT. D maps were generated using a local-deposition algorithm. Contrast-enhanced CT or magnetic resonance imaging scans of the liver were registered to 90 Y-SPECT/CT, and all tumors larger than 2.5 cm diameter (53 tumors) were segmented. Tumor mean D and BED (Dmean and BEDmean) and dose volume coverage from 0% to 100% in 10% steps (D0-D100 and BED0-BED100) were extracted. Tumor response was evaluated on follow-up using World Health Organization (WHO), Response Evaluation Criteria in Solid Tumors (RECIST), and modified RECIST (mRECIST) criteria. Differences in dose metrics for responders and nonresponders were assessed using the Mann-Whitney U test. A univariate logistic regression model was used to determine tumor dose metrics that correlated with tumor response. Correlations among tumor size, tumor Dmean, and tumor dose heterogeneity (defined as the coefficient of variation) were assessed., Results: The objective response rates were 14 of 53, 15 of 53, and 30 of 53 for WHO, RECIST, and mRECIST criteria, respectively. WHO and RECIST response statuses did not correlate with D or BED. For mRECIST responders and nonresponders, D and BED were significantly different for Dmean, D20 to D80, BEDmean, and BED0 to BED80. Threshold doses (and the 95% confidence interval) for 50% probability of mRECIST response (D 50% ) were 160 Gy (123-196 Gy) for Dmean and 214 Gy (146-280 Gy) for BEDmean. Tumor dose heterogeneity significantly correlated with tumor volume. No statistically significant association between Dmean to normal liver and complications related to bilirubin, albumin, or ascites was observed., Conclusions: Hepatocellular carcinoma tumor dose-response curves after 90 Y-radioembolization with glass microspheres showed Dmean of 160 Gy and BEDmean of 214 Gy for D 50% with a positive predictive value of ∼70% and a negative predictive value of ∼62%. No complications were observed in our patient cohort for normal liver Dmean less than 44 Gy., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Purpose: 90 Y-microsphere selective internal radiation therapy ( 90 Y-SIRT or 90 Y-radioembolization) is used in the management of unresectable liver tumors. 90 Y-SIRT presents a unique situation where the total 90 Y activity inside the liver can be determined with high accuracy (> 95%). 90 Y bremsstrahlung single-photon emission computed tomography (SPECT)/computed tomography (CT) can be self-calibrated to provide quantitative images that facilitate voxel-level absorbed dose calculations. We investigated the effects of different approaches for 90 Y-SPECT self-calibration on the quantification of absorbed doses following 90 Y-SIRT., Methods: 90 Y bremsstrahlung SPECT/CT images of 31 patients with hepatocellular carcinoma, collected following 90 Y-SIRT, were analyzed, yielding 48 tumor and 31 normal liver contours. We validated the accuracy of absorbed doses calculated by a commercial software against those calculated using Monte Carlo-based radiation transport. The software package was used to analyze the following definitions of SPECT volume of interest used for 90 Y-SPECT self-calibration: (a) SPECT field-of-view (FOV), (b) chest-abdomen contour, (c) total liver contour, (d) total liver contour expanded by 5 mm, and (e) total liver contour contracted by 5 mm. Linear correlation and Bland-Altman analysis were performed for tumor and normal liver tissue absorbed dose volume histogram metrics between the five different approaches for 90 Y-SPECT self-calibration., Results: The mean dose calculated using the commercial software was within 3% of Monte Carlo for tumors and normal liver tissues. The tumor mean dose calculated using the chest-abdomen calibration was within 2% of that calculated using the SPECT FOV, whereas the doses calculated using the total liver contour, expanded total liver contour, and contracted total liver contour were within 68%, 47%, and 107%, respectively, of doses calculated using the SPECT FOV. The normal liver tissue mean dose calculated using the chest-abdomen contour was within 1.3% of that calculated using the SPECT FOV, whereas the doses calculated using the total liver contour, expanded total liver contour, and contracted total liver contour were within 73%, 50%, and 114%, respectively, of doses calculated using the SPECT FOV., Conclusions: The mean error of < 3% for commercial software can be considered clinically acceptable for 90 Y-SIRT dosimetry. Absorbed dose quantification using 90 Y-SPECT self-calibration with the chest-abdomen contour was equivalent to that calculated using the SPECT FOV, but self-calibration with the total liver contour yielded substantially higher (~70%) dose values. The large biases revealed by our study suggest that consistent absorbed dose calculation approaches are essential when comparing 90 Y-SIRT dosimetry between different clinical studies., (© 2017 American Association of Physicists in Medicine.)

Purpose: To quantify differences that exist between dosimetry models used for 90 Y selective internal radiation therapy (SIRT)., Methods and Materials: Retrospectively, 37 tumors were delineated on 19 post-therapy quantitative 90 Y single photon emission computed tomography/computed tomography scans. Using matched volumes of interest (VOIs), absorbed doses were reported using 3 dosimetry models: glass microsphere package insert standard model (SM), partition model (PM), and Monte Carlo (MC). Univariate linear regressions were performed to predict mean MC from SM and PM. Analysis was performed for 2 subsets: cases with a single tumor delineated (best case for PM), and cases with multiple tumors delineated (typical clinical scenario). Variability in PM from the ad hoc placement of a single spherical VOI to estimate the entire normal liver activity concentration for tumor (T) to nontumoral liver (NL) ratios (TNR) was investigated. We interpreted the slope of the resulting regression as bias and the 95% prediction interval (95%PI) as uncertainty. MC NL single represents MC absorbed doses to the NL for the single tumor patient subset; other combinations of calculations follow a similar naming convention., Results: SM was unable to predict MC T single or MC T multiple (p>.12, 95%PI >±177 Gy). However, SM single was able to predict (p<.012) MC NL single , albeit with large uncertainties; SM single and SM multiple yielded biases of 0.62 and 0.71, and 95%PI of ±40 and ± 32 Gy, respectively. PM T single and PM T multiple predicted (p<2E-6) MC T single and MC T multiple with biases of 0.52 and 0.54, and 95%PI of ±38 and ± 111 Gy, respectively. The TNR variability in PM T single increased the 95%PI for predicting MC T single (bias = 0.46 and 95%PI = ±103 Gy). The TNR variability in PM T multiple modified the bias when predicting MC T multiple (bias = 0.32 and 95%PI = ±110 Gy)., Conclusions: The SM is unable to predict mean MC tumor absorbed dose. The PM is statistically correlated with mean MC, but the resulting uncertainties in predicted MC are large. Large differences observed between dosimetry models for 90 Y SIRT warrant caution when interpreting published SIRT absorbed doses. To reduce uncertainty, we suggest the entire NL VOI be used for TNR estimates when using PM., Competing Interests: Notification: AM receives research support from BTG and Sirtex., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Purpose: To develop a practical background compensation (BC) technique to improve quantitative (90)Y-bremsstrahlung single-photon emission computed tomography (SPECT)/computed tomography (CT) using a commercially available imaging system., Methods: All images were acquired using medium-energy collimation in six energy windows (EWs), ranging from 70 to 410 keV. The EWs were determined based on the signal-to-background ratio in planar images of an acrylic phantom of different thicknesses (2-16 cm) positioned below a (90)Y source and set at different distances (15-35 cm) from a gamma camera. The authors adapted the widely used EW-based scatter-correction technique by modeling the BC as scaled images. The BC EW was determined empirically in SPECT/CT studies using an IEC phantom based on the sphere activity recovery and residual activity in the cold lung insert. The scaling factor was calculated from 20 clinical planar (90)Y images. Reconstruction parameters were optimized in the same SPECT images for improved image quantification and contrast. A count-to-activity calibration factor was calculated from 30 clinical (90)Y images., Results: The authors found that the most appropriate imaging EW range was 90-125 keV. BC was modeled as 0.53× images in the EW of 310-410 keV. The background-compensated clinical images had higher image contrast than uncompensated images. The maximum deviation of their SPECT calibration in clinical studies was lowest (<10%) for SPECT with attenuation correction (AC) and SPECT with AC + BC. Using the proposed SPECT-with-AC + BC reconstruction protocol, the authors found that the recovery coefficient of a 37-mm sphere (in a 10-mm volume of interest) increased from 39% to 90% and that the residual activity in the lung insert decreased from 44% to 14% over that of SPECT images with AC alone., Conclusions: The proposed EW-based BC model was developed for (90)Y bremsstrahlung imaging. SPECT with AC + BC gave improved lesion detectability and activity quantification compared to SPECT with AC only. The proposed methodology can readily be used to tailor (90)Y SPECT/CT acquisition and reconstruction protocols with different SPECT/CT systems for quantification and improved image quality in clinical settings.