Combination approaches using systemic immunotherapy agents are now standard of care for patients with advanced-stage hepatocellular carcinoma (HCC), resulting in improved overall survival. However, even with optimal systemic regimens, fewer than 40% of cases respond to treatment, presumably due to resistance mechanisms, including antidrug antibodies and acquired resistance related to alterations in the tumor immune microenvironment (TIME). As a result, new strategies are needed to improve immunotherapeutic efficacy in this setting. Early investigations into the local and systemic effects of yttrium 90 (90Y) radioembolization using resin and glass microspheres demonstrated activation of both innate and adaptive immune systems, leading to sustained therapeutic efficacy in a subgroup of patients with HCC undergoing curative surgical resection after downstaging procedures. Preliminary prospective and retrospective studies have confirmed the safety of combining liver-directed interventions with immunotherapy. Based on these findings, clinical trials are being designed to evaluate the efficacy of different therapeutic strategies combining 90Y radioembolization and immune checkpoint inhibitor therapy. The Society of Interventional Oncology is committed to advancing research on how local-regional therapies influence the TIME and systemic inflammatory response. This review aims to inform the interventional and medical oncology community about essential considerations and strategies for implementing these combination therapies involving 90Y radioembolization and immunotherapy.

PURPOSE:AvidinOX™ forms a long-lasting artificial receptor that supports effective in vivo binding of circulating biotinylated therapeutic 177Lu-DOTA-biotin. We investigated the biodistribution and radiation dosimetry of 177Lu-DOTA-biotin in patients with solid tumors following image-guided intratumoral AvidinOX administration. METHODS:Three patients received intratumoral injections of AvidinOX and two cycles of intravenous administration of 177Lu-DOTA-biotin over a period of 2 weeks. Multi-time-point whole-body planar and SPECT/CT imaging was performed post infusion. Blood and urine samples were collected over 7 days, and organ radiation doses were estimated using the Medical Internal Radiation Dose methodology. RESULTS:Sequential imaging demonstrated favorable tumor-to-background ratios and sustained uptake of 177Lu-DOTA-biotin within the pretargeted lesions, confirming effective localization and prolonged retention. Most of the administered activity was excreted via urine within 4 h post infusion. The absorbed tumor radiation dose ranged from 3.96 to 50.37 Gy, while bone marrow (0.15-0.22 Gy) and kidney (0.66-1.84 Gy) doses remained below established safety thresholds. There were no serious adverse events. CONCLUSIONS:Intratumoral AvidinOX achieved effective and durable localization of 177Lu-DOTA-biotin without exceeding the maximum allowable radiation absorbed dose to critical organs. These first-in-human dosimetric data provide quantitative insight into tumor retention, off-target exposure, and therapeutic potential across solid tumors, supporting the rational design of future radionuclide therapy trials.

The microsphere spatial distribution following Yttrium-90 radioembolization (90Y-RE) is inherently nonuniform, resulting in substantial microscopic dose heterogeneity not captured by conventional macroscopic dosimetry models. The motivation for this study was to build a robust framework to further understand the relationship between microdosimetry and macrodosimetry-based clinical outcomes. In this study, a stochastic microsphere deposition algorithm sampled histologically-derived cumulative distribution functions (CDFs) governing microsphere cluster diameter (Cdia), distance between clusters (Cdist), and cluster population (Cpop). Six unique models were generated to examine the impact of algorithm complexity on the corresponding absorbed dose distribution, ranging from a completely uniform to fully stochastic reference model. A two-sample statistical Kolmogorov-Smirnov test compared Cdia, Cdist, and Cpop derived separately from discrete and continuous CDFs. Microdosimetry calculations were performed by convolving a high-resolution dose-voxel kernel with each model. The mean absorbed dose Dmean and various dose-volume metrics (Dx,x=1,5,10,50,90,95,99) were calculated and compared to the reference model to assess the impact of algorithm complexity on dose metric error (Ex). Published median values of Cdia, Cdist, and Cpop agreed well with simulated counterparts. There were no statistically significant differences in sampling between discrete and continuous CDFs for Cdia (p=0.083), Cdist (p=0.104), and Cpop (p=0.094). Convolution with the90Y dose-voxel kernel resulted a -0.3% deviation compared to a single compartment dose estimate. Model comparisons suggest that sampling Cdist​ is critical for accurately modeling low-dose regions (E99=16%), while sampling Cpop is critical for resolving absorbed dose hot spots (E1=-12%). In contrast, sampling from Cdia​ had minimal impact on model accuracy. The results of this study provide the necessary framework to develop an improved understanding of the relationship between microdosimetry and macrodosimetry-based clinical outcomes following90Y-RE.

AIM:To evaluate the ability of quantitative molecular breast imaging (MBI) parameters obtained early during neoadjuvant systemic therapy (NST) in breast cancer patients to predict pathologic complete response (pCR) at surgery. METHODS:Patients with invasive breast cancer (T1-T4, N0-N3, M0) planned to receive NST followed by surgery were enrolled in a prospective Institutional Review Board approved trial (NCT #02324387). MBI was performed at baseline and after 2 cycles of NST. MBI images were quantified by drawing regions of interest over tumors to compute three quantitative MBI uptake metrics for correlation with pCR and residual cancer burden (RCB): MBI-specific standardized uptake value (SUVMBI), tumor to background ratio (TBR), and tumor volume. MBI metrics were correlated with pCR and RCB using the Wilcoxon Rank Sum test or Fisher's exact test. RESULTS:A total of 69 patients (median 48, range 30-77 years) were included in the analysis. Absolute decrease of 1.3 and 48% change of SUVMBI was able to differentiate pCR vs nonpCR after 2 cycles of NST with AUC 0.76 and 0.77, and RCB 0/1 (response) versus RCB 2/3 (nonresponse) with AUC of 0.79 and 0.82, respectively. Absolute and percent changes in TBR were predictive of pCR and RCB with an AUC of 0.74 and 0.76, respectively. CONCLUSION:SUVMBI and TBR changes after 2 cycles of NST correlate with and may predict pCR in patients with locally advanced breast cancer. Quantitative MBI parameters are novel promising imaging biomarkers for early prediction of pCR optimizing management of NST in patients with breast cancer.

Purpose:To describe the safety and efficacy of Yttrium-90 transarterial radioembolization (Y90-TARE) in patients with fibrolamellar hepatocellular carcinoma (FL-HCC). Patients and Methods:This is a retrospective study of patients with FL-HCC treated with Y90-TARE in a single tertiary cancer center. Y90-TARE was performed using Y90 glass or resin microspheres. Treatment response was evaluated at 1, 3, and 6 months using the modified Response Evaluation Criteria in Solid Tumors (mRECIST) guidelines. Electronic medical records were retrospectively reviewed to evaluate clinical outcomes, complications, tumor response on imaging, overall survival (OS), and progression-free survival (PFS). MIM Software (v7.1, Cleveland, OH) was used for dosimetry analysis and contouring. Results:Seven patients (5 females, 2 males; median age at the time of Y90-TARE: 24, range: 16-77 years) with FL-HCC underwent nine Y90-TARE procedures. The median progression-free survival (PFS) was 9.0 months, and the median overall survival (OS) was 15.8 months. Partial response (PR) was observed in 86% of patients at 3 months and 100% of evaluable patients at 6 months. One patient underwent successful liver transplantation, and another received hepatectomy after treatment. No adverse events grade 3 or greater were reported within 30 days. One patient developed a hepatic abscess two months post-procedure, and another developed a tumor to duodenum fistula three months after Y90-TARE. The median absorbed tumor dose was 405 Gy (mean: 579 ± 442 Gy; range: 109-1362 Gy), and the median absorbed dose to perfused normal liver was 83 Gy (mean: 96 ± 41 Gy; range: 63.5-190 Gy). The median administered activity was 3.85 GBq, with a median lung shunt fraction of 4.59% and a median lung dose of 6.4 Gy. The study is limited by its retrospective design and small sample size in this rare tumor cohort. Conclusion:Treatment of FL-HCC patients with unresectable tumors with 90Y-TARE is safe and shows a favorable response to treatment.

In voxel-based dosimetry, dose-voxel kernels (DVKs) represent the absorbed dose in a target voxel per decay in a source voxel. In this work, we aimed to validate DVKs generated using Particle and Heavy Ion Transport Code System (PHITS) as a first step in establishing a quantitative SPECT/CT-based dosimetry framework for selective internal radiation therapy (SIRT). A 1-MBq source of 90Y, 153Sm, 177Lu, 188Re, and 166Ho located in central cubic voxels of 1 mm, 3 mm, and 6 mm dimension within soft tissue (1.04 g⋅cm−³), was simulated using 2.5 × 10⁷ histories in PHITS. The DVK results were compared to published data (Lanconelli et al., 2012). In a pilot study, 17 MBq of 153Sm microspheres were injected into a liver tumor-bearing rat and imaged 24 h later using SPECT/CT. SPECT/CT images were then converted to cumulated activity and convolved with a 153Sm DVK using Fast Fourier Transform in MATLAB to create an absorbed dose map. As expected, DVKs for the radionuclides showed a steep decrease from the source voxel to the maximum continuous slowing down approximation (CSDA) of beta components. Beyond the CSDA, gamma and bremsstrahlung contributed minimally (10⁻⁶ to 10⁻⁴) to voxel doses. Observed DVK changes as voxel size increased were in good agreement with published data, with differences in source voxel ranging from 1 to 24

OBJECTIVES:The practice parameter was revised collaboratively by the American College of Radiology (ACR), the American Brachytherapy Society (ABS), the American College of Nuclear Medicine (ACNM), the American Radium Society (ARS), the Society of Interventional Radiology (SIR), and the Society of Nuclear Medicine and Molecular Imaging (SNMMI). This document summarizes current evidence-based guidelines for the administration of Yttrium radioembolic therapy to the liver, including training requirements, evidence-based guidelines for administration, and safe practice for administration. METHODS:This practice parameter was revised according to the process described under the heading The Process for Developing ACR Practice Parameters and Technical Standards on the ACR website ( https://www.acr.org/ClinicalResources/Practice-Parameters-and-Technical-Standards ) by the Committee on Practice Parameters-Interventional and Cardiovascular Radiology of the ACR Commission on Interventional and Cardiovascular, Committee on Practice Parameters and Technical Standards-Nuclear Medicine and Molecular Imaging of the ACR Commission on Nuclear Medicine and Molecular Imaging and the Committee on Practice Parameters-Radiation Oncology of the ACR Commission on Radiation Oncology in collaboration with the ABS, the ACNM, the ARS, the SIR, and the SNMMI. RESULTS:This review seeks not to be a comprehensive discussion of radiotherapy to the liver, but rather, seeks to provide a parameter for safe and effective therapy. We discuss the qualifications of physicians involved in this therapy, basic indications, contraindications, procedural work-up, safe-handling, and regulatory requirement for the administration of selective internal radiation therapy to patients that are likely to benefit. The goal of this document is not to define which patients are best treated by these therapies, as this is best determined for individual patients after multidisciplinary review. A consistent and evidence-based approach to therapy, however, would benefit all patients who are offered this therapy. This document seeks to provide a framework for current best practices for the administration of the 2 currently available radioembolization devices. CONCLUSIONS:As Yttrium-90 radiotherapy to the liver occupies a growing role in the treatment of primary and metastatic liver cancer, this review seeks to assist clinicians of all involved specialties to optimize the efficacy and safety of these procedures.

The TheraSphere Global Steering Committee reconvened to review clinical data and address knowledge gaps related to treatment and dosimetry in non-HCC indications using Yttrium-90 (90Y) glass microspheres. A PubMed search was performed. References were reviewed and adjudicated by the Delphi method. Recommendations were graded according to the degree of recommendation and strength of consensus. Dosimetry focused on a mean dose approach, i.e., aiming for an average dose over either single or multicompartment volumes of interests. Committee discussion and consensus focused on optimal patient selection, disease presentation, liver function, tumour type, tumour vascularity, and curative/palliative treatment intent for intrahepatic cholangiocarcinoma (iCCA) and colorectal and neuroendocrine carcinoma liver metastases (mCRC, mNET). For all indications, single compartment average perfused volume absorbed dose ≥ 400 Gy is recommended for radiation segmentectomy and 150 Gy for radiation lobectomy. Single compartment 120 Gy for uni- and bilobar treatment reflects current clinical practice, which results in variable tumour and normal tissue absorbed doses. Therefore, multicompartment dosimetry is recommended for uni- and bilobar treatment, aiming for maximum 75 Gy to normal tissue and 150–200 Gy (mCRC, mNET), ≥ 205 (iCCA) tumour absorbed doses. These dose thresholds are preliminary and should be used with caution accounting for patient specific characteristics. Consensus recommendations are provided to guide clinical and dosimetry approaches for 90Y glass microsphere radioembolization in iCCA, mCRC and mNET. Clinical trial number: not applicable.

RATIONALE AND OBJECTIVES:Best practices for quantifying longitudinal changes in 99m Tc-sestamibi uptake with molecular breast imaging (MBI) have not been established. The objective of this work is to quantify the variability of tumor-to-normal tissue 99m Tc-sestamibi uptake measurements in patient data and the resulting impact on categorizing uptake changes throughout neoadjuvant systemic therapy (NST). MATERIALS AND METHODS:In 60 patients with locoregional breast cancer undergoing NST, tumor-to-normal-tissue ratios of average contour counts ( ) and activity concentrations ( ) were calculated from physician contours on craniocaudal and mediolateral-oblique MBI images acquired at pre-NST, mid-NST, and post-NST with a commercial dual-headed system. Measurement variability was quantified in pre-NST images by using different contours and detector views. This analysis was then used to define patient-specific thresholds above which calculated and values at mid-NST and post-NST imaging had 'changed' from pre-NST values. RESULTS:Pre-NST values ranged from 1-5 to 1-100 and in general decreased by 10-30% at mid-NST and by 50-70% at post-NST. uncertainty was significantly higher than uncertainty (53% vs. 35% median value; paired t -test; P  < 0.007), driven primarily by normal-tissue contour placement within the heterogeneous signal in normal breast parenchyma. In paired comparisons, a significantly higher number of cases 'changed' when the metric was derived from a single image instead of averaged across images (McNemar's test, P  < 0.0125). CONCLUSION:By ensuring consistent acquisition conditions and standardizing contour definitions, robust metrics of tumor and normal-tissue uptake can be extracted from heterogenous clinical MBI data for longitudinal quantitative evaluations.

Background: Following yttrium-90 radioembolization (90Y-RE), 90Y-PET/CT and 90Y-SPECT/CT imaging provide the means to calculate the voxelized absorbed dose distribution. Given the widespread use of the two imaging modalities and lack of well-established standardized dosimetry protocols for 90Y-RE, there is a clinical need to systematically investigate and evaluate differences in the performance of voxel-based dosimetry between 90Y-PET/CT and 90Y-SPECT/CT. Purpose: To quantitatively analyze and compare 90Y-PET/CT and 90Y-SPECT/CT-based dosimetry following 90Y-RE. Methods: 90Y-PET/CT and 90Y-SPECT/CT imaging was acquired for 35 patients following 90Y-RE with TheraSphere for the treatment of unresectable hepatocellular carcinoma. Dosimetry was performed using the local deposition method with known activity and the mean dose (Dmean) was calculated for perfused liver volumes (PV), tumors (T), and perfused normal livers (NL). Additionally, the absorbed dose to x% of the volume (Dx, x is an element of [5%, 10%, & mldr;, 90%, 95%]) and the volume receiving y Gy (Vy, y is an element of [10 Gy, 20 Gy, & mldr;, 190 Gy, 200 Gy]) were calculated for T and NL, respectively. Dose metrics were compared using linear regression, Bland-Altman analysis, and statistical testing. Results: Both 90Y-SPECT/CT and 90Y-PET/CT-based tumor Dmean were strongly correlated (R2 >= 0.90) with Dx, excluding metrics on the extrema. Intra-modality comparisons of various Dx and Vy metrics yielded statistically significant differences (ANOVA, p < 0.001) for both90Y-PET/CT and 90Y-SPECT/CT. Based on statistical testing, only Dx metrics separated by greater than 20%-30% coverage, and only Vy metrics separated by greater than 40-70 Gy, reported significant differences. For PV, there was a strong correlation (R2 >= 0.99) between Dmean derived separately from 90Y-PET/CT and 90Y-SPECT/CT imaging. The strength of the correlation was slightly reduced for T and NL with R2 = 0.91 and R2 = 0.95, respectively. For PV, the mean bias +/- standard error (SE) and 95% limits of agreement (LOA) between Dmean from the two modalities was effectively zero with -0.8 +/- 0.4% (+/- 2.5%). For T and NL, the mean bias +/- SE (+/- LOA) was -14.5 +/- 3.7% (+/- 24%) and 9.4 +/- 4.7% (+/- 27%), respectively. Conclusion: The strong correlation between Dmean and Dx suggests information from multiple dose metrics (e.g., D70 and Dmean) is largely redundant when establishing dose-response relationships in 90Y-RE. Dmean is highly correlated between 90Y-PET/CT and 90Y-SPECT/CT-based dosimetry, for all liver VOIs. Relative to 90Y-SPECT/CT, 90Y-PET/CT, on average, yielded higher Dmean to tumors (14%) and lower Dmean to perfused normal livers (9%). Absorbed dose differences for perfused liver volumes between 90Y-SPECT/CT and 90Y-PET/CT were negligible.

Focus on Uniformity, Not Dose: The Folly of Yttrium-90 Transarterial Radioembolization Dose-Escalation StudiesJournal of Vascular and Interventional RadiologyPreviewUnlike molecular-mediated therapies such as chemotherapy and immunotherapy, radiation therapy will always result in cell death if an adequate dose is delivered. Hence, delivering such a dose to all cells in a tumor while limiting the dose to normal tissue is the focus of therapy. A major advantage of transarterial radioembolization compared with external beam radiation therapy is the ability to limit the dose to normal tissue via the endovascular selection of a specific tumor angiosome. However, this endovascular approach is a double-edged sword because it inevitably results in a nonuniform distribution of dose compared to external beam radiation therapy, potentially compromising tumor control. Full-Text PDF

PURPOSE:To determine 6-month interim safety, effectiveness, and multimodal imageability of imageable glass microsphere yttrium-90 (90Y) 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 90Y 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.

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 3 10 on both the CRC-15R and the CRC-55tR dose calibrators (errors within 6 0.5%) and indirectly with an exposure-rate reading at 30 cm using conversion factor 0.664 6 0.003 GBq/(mR/h) (R2 R 2 5 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.

Personalised multi-compartment dosimetry based on [99mTc]Tc-MAA is a valuable tool for planning 90Y radioembolization treatments. The establishment and effective application of dose–effect relationships in yttrium-90 (90Y) radioembolization requires [99mTc]Tc-MAA SPECT quantification ideally independent of clinical site. The purpose of this multi-centre phantom study was to evaluate inter-site variability of [99mTc]Tc-MAA imaging and evaluate a standardised imaging protocol. Data was obtained from the TARGET study, an international, retrospective multi-centre study including 14 sites across 8 countries. The impact of imaging related factors was estimated using a NEMA IQ phantom (representing the liver), and a uniformly filled cylindrical phantom (representing the lungs). Imaging was performed using site-specific protocols and a standardized protocol. In addition, the impact of implementing key image corrections (scatter and attenuation correction) in the site-specific protocols was investigated. Inter-site dosimetry accuracy was evaluated by comparing computed Lung Shunt Fraction (LSF) measured using planar imaging of the cylindrical and NEMA phantom, and contrast recovery coefficient (CRC) measured using SPECT imaging of the NEMA IQ phantom. Regarding the LSF, inter-site variation with planar site-specific protocols was minimal, as determined by comparing computed LSF between sites (interquartile range 9.6–10.1

This article is intended to introduce nuclear medicine technologists (NMTs) to the nuances of radiopharmaceutical therapy clinical trials. Here, we outline the potential roles and responsibilities of the NMT in clinical trials and provide context on different aspects of radionuclide therapy. The regulatory process involving investigational therapeutic radiopharmaceuticals is seldom taught to NMT students, nor is it included in the entry-level nuclear medicine certification examinations. Often, NMTs must spend significant time preparing for therapeutic clinical trials on their own, using multiple academic sources, seeking advice from various health care professionals, and reviewing numerous trial-specific manuals to recognize the detailed requirements. The emergence of theranostics has spurred an increase in the development of therapeutic radiopharmaceuticals. Investigators with a robust nuclear medicine background are required to help develop successful therapeutic clinical trials, and well-informed NMTs are crucial to the success of such trials. This article follows a series of previous publications from the Society of Nuclear Medicine and Molecular Imaging Clinical Trials Network research series for technologists and is intended to guide the investigational radiopharmaceutical landscape.

Background: Yttrium-90 (Y-90) positron emission tomography (PET)/computed tomography (CT) imaging is increasingly being used to perform tumor (T) and normal liver (NL) voxel dosimetry after Y-90-radioembolization (Y-90-RE). Yet, the accuracy of in vivo Y-90-PET/CT imaging, subject to motion blur and co-registration inaccuracies, and Y-90-PET/CT dose quantification, subject to availability of different voxel dosimetry algorithms, are not well understood. Purpose: The purpose of this study was to investigate the accuracy of Y-90-PET/CT-based activity estimates following Y-90-RE and characterize differences between Y-90-PET/CT-based voxel dosimetry algorithms. Methods: Thirty-five patients underwent Y-90-PET/CT imaging after Y-90-RE with TheraSphere. The net administered Y-90 activity (A(admin)) was determined using a dose calibrator and pre- and post-procedure exposure rate measurements. The summation of image-based activity (A(image)) was extracted from perfused volume (PV) and 3D-isotropically 2-cm expanded PV contour (PV+2 cm). Absorbed doses were calculated using voxel S-value (VSV), local deposition method (LDM), and LDM with known activity (LDMKA) dosimetry algorithms. Linear regression and Bland-Altman analysis quantified the relationship between A(image) and A(admin) and between mean dose estimates (D-LDM, D-VSV, DLDM-KA) for PV, T, and perfused NL volumes. Results: While A(admin) and A(image) in PV were highly correlated (R-2 > 0.95), the mean bias +/- standard error (SE) and (95% limits of agreement, LOA) was significantly non-zero with -22.7 +/- 4.7% (+/- 28.4%). In PV+2 cm, the mean bias +/- SE (+/- LOA) decreased to 1.3 +/- 3.4% (+/- 18.0%) consistent with zero mean error. D-LDM and D-VSV were highly correlated (R-2 > 0.99) for all volumes of interest (VOIs) and the mean bias +/- SE (+/- LOA) was 2.2 +/- 0.2% (+/- 1.0%), 0.7 +/- 0.4% (+/- 2.8%), and 3.2 +/- 0.5% (+/- 2.8%) for PV, T, and NL, respectively. DLDM-KA and D-VSV were correlated with R-2 = 0.86, 0.80, and 0.86 for PV, T, and NL, respectively. The mean bias +/- SE (+/- LOA) between DLDM-KA and D-VSV was significantly non-zero with -19.6 +/- 5.1% (+/- 31.0%), -20.8 +/- 4.4% (+/- 29.0%), and -18.1 +/- 5.3% (+/- 31.1%) for PV, T, and NL, respectively. Conclusions: The summation of A(image) in PV was underestimated relative to A(admin). Only by accounting for respiratory motion, limited spatial resolution, and PET/CT co-registration errors through VOI expansion was A(image), on average, equal to A(admin). The differences between D-LDM and D-VSV were not clinically relevant, though DLDM-KA was approximately 20% greater than D-VSV. Given the high quantitative accuracy of dose calibrators and challenges associated with accurate Y-90-PET/CT quantification, LDMKA is the preferred algorithm for accurate Y-90-PET/CT-based dosimetry following Y-90-RE.

Pre-treatment [99mTc]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 [99mTc]TcMAA-based segmentation of tumor and normal tissue compartments. Included patients had HCC treated by glass [90Y]yttrium microspheres, ≥ 1 tumor, ≥ 3 cm diameter and [99mTc]TcMAA SPECT/CT imaging before treatment. Segmentation was performed retrospectively using dedicated dosimetry software: (1) anatomic (diagnostic CT/MRI-based), and (2) [99mTc]TcMAA threshold-based (i.e., using an activity-isocontour threshold). CT/MRI was co-registered with [99mTc]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. A total of 209 patients were enrolled. Total perfused tumor and normal tissue volumes were larger when using anatomic versus [99mTc]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