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Purpose: To evaluate dosimetry, dose-response and dose-toxicity relationships for holmium-166 ( 166 Ho) radioembolisation in patients with hepatocellular carcinoma (HCC)., Methods: Thirty-one patients with hepatocellular carcinoma were included in the HEPAR Primary study (NCT03379844, registered on December 20th, 2017) and underwent 166 Ho-microspheres radioembolisation. Linear mixed models assessed the association between tumour absorbed doses and response based on mRECIST both on tumour and patient level. Preliminary tumour absorbed dose thresholds were estimated based on predictive value. Linear regression models assessed the association between non-tumour absorbed dose and Common Terminology Criteria for Adverse Events version 4.03., Results: Median tumour absorbed dose (tumour level) was 95.5 Gy (range 44-332 Gy). Median non-tumour absorbed dose based on whole liver volume was 19 Gy (range 3 - 48 Gy) and based on target liver volume was 30 Gy (range 13 - 54 Gy). There was a significant association between non-tumour absorbed dose and toxicity. Tumours with partial response/complete response (PR/CR, responders) received a 41% higher absorbed dose than tumours with progressive disease/stable disease (PD/SD, non-responders) (95%CI: 2%-93%, p = 0.04). A predictive value of 90% for tumour response was observed at a tumour absorbed dose threshold of 155 Gy, 100% predictive value was achieved at 184.5 Gy., Conclusion: This study confirms a positive relationship between tumour absorbed dose and response and between non-tumour absorbed dose and toxicity. Dose thresholds found in this study can serve as a basis for personalized dosimetry in HCC patients treated with 166 Ho-microspheres., Competing Interests: Declarations. Ethics approval: This clinical study was approved by the Medical Ethics Committee of University Medical Centre Utrecht and Erasmus Medical Centre and by the institutional radiation protection committee. Furthermore, this study was performed in concordance with Good Clinical Practice and the declaration of Helsinki. Consent to participate: All participants provided written, informed consent before undergoing any study-specific activity. Conflicts of interest: Margot Reinders-Hut is currently employed by Genmab B.V., acted as a speaker for Boston Scientific. Marnix Lam acts as a consultant for Terumo, Quirem Medical and Boston Scientific, receives research support from Terumo, Quirem Medical and Boston Scientific. Maarten Smits and Arthur Braat are consultants for Terumo. The department of Radiology and Nuclear Medicine of the University Medical Centre Utrecht receives royalty payments from Quirem Medical., (© 2024. The Author(s).)

Objective: To investigate the prognostic value of baseline European Association of Nuclear Medicine Research Ltd. (EARL) standardized [ 18 F]fluorodeoxyglucose positron emission tomography-computed tomography ([ 18 F]FDG PET-CT) quantitative values for survival and to evaluate cutoff values identified in other studies., Materials and Methods: Pediatric and adolescent patients with high-grade osteosarcoma were included. Baseline [ 18 F]FDG PET-CT, with EARL-accredited reconstructions, was the standard diagnostic staging procedure. Cox proportional hazard analysis for event-free survival (EFS) and overall survival (OS) was performed with clinical prognostic factors. Kaplan-Meier analysis and log-rank tests were applied to investigate the prognostic performance of the [ 18 F]FDG PET indices., Results: In total, 66 patients were included in this study. In the univariable Cox regression analysis, peak lean-body mass corrected SUV (SUL peak ) (hazard ratio (HR): 1.04), total lesion glycolysis (TLG) (HR: 1.0), and metabolic tumor volume (MTV) (HR: 1.0) were not associated with EFS or OS. Log-rank analysis showed a significant difference in EFS for all SUL max and SUL peak cutoffs. For MTV total the maximum Youden, and for TLG total, the maximum Youden and maximally selected rank cutoff resulted in a significant EFS difference. No cutoff for any measure showed a significant difference in OS between the groups. ROC curves for event status had an AUC of 0.67, 0.66, 0.64, and 0.64 for SUL max , SUL peak , MTV total, and TLG total , respectively., Conclusion: In this study, the baseline EARL-standardized [ 18 F]FDG PET indices of children and adolescents with osteosarcoma were not prognostic of EFS or OS. The proposed prognostic cutoffs from earlier studies suffer from important technical and statistical issues., Key Points: Question Prognostic value of baseline [ 18 F]FDG PET-CT imaging markers have been reported for histologic response and survival in high-grade osteosarcoma but have not been validated for clinical practice. Findings Baseline SUV peak , TLG total , and MTV total measured on EARL-accredited reconstructions were not prognostic factors for survival in pediatric and adolescent patients with high-grade osteosarcoma. Clinical relevance A wide range of values for SUV peak and SUV max cutoffs with similar prognostic value were identified, questioning the value of a single proposed cutoff. Lack of validation, with important technical and statistical issues of proposed prognostic cutoffs, limits clinical implementation., Competing Interests: Compliance with ethical standards. Guarantor: The scientific guarantor of this publication is R.E. Conflict of interest: A.B. acted as a consultant for Boston Scientific, Terumo, and GE Healthcare, receiving research support from Boston Scientific, Terumo, and Ariceum Therapeutics. J.M. reports personal/consulting fees from Bayer, GlaxoSmithKline, and Merck. R.E., R.D., J.R., B.K., S.H., M.S., L.v.d.H., and L.H. have no relevant financial or non-financial interests to disclose. Statistics and biometry: One of the authors (R.D.) is a statistician. Informed consent: Data were retrospectively collected as part of the biobank and data access initiative of the institute, for which all included patients and/or their legal representatives provided signed informed consent. Ethics approval: The Institutional Medical Ethics Review Board confirmed that the Medical Research Involving Human Subjects Act (WMO) did not apply to the study (research protocol number 23-207/DB). Study subjects or cohorts overlap: No study subjects or cohorts have been previously reported. Methodology: Retrospective Prognostic study Performed at one institution, (© 2025. The Author(s).)

Background: To study the feasibility of hepatobiliary scintigraphy (HBS) to improve selection and planning of patients with hepatocellular carcinoma (HCC) treated with holmium-166 ( 166 Ho)-microspheres radioembolization., Results: Thirty-one patients with HCC were included and treated with 166 Ho- radioembolization as part of a prospective phase 2 study. Twenty-seven patients were eligible for analysis, 67% had a cirrhotic liver morphology on imaging, 70% had multifocal disease and 51% had bilobar disease. None of the patients had clinical signs of liver decompensation (Child Pugh ≤ B7, median MELD 9 or ALBI - 2.55). Global and regional hepatic function was based on manual delineation of HBS using 200 MBq 99m Tc-mebrofenine, acquired during screening and approximately three months after 166 Ho-radioembolization, referred to as liver clearance rate (LCR). In line with LCR at baseline, a significant correlation was found between LCR and lab results, including bilirubin, albumin, ALT, MELD-score, and ALBI-score (p < 0.05) during follow-up. HBS showed a significant decrease in median LCR (-16%; p = 0.0017) and volume (-17%; p = 0.0027) in the treated liver, without a significant increase in the non-treated liver. Median relative change in overall LCR in non-cirrhotics was 0% (range - 23-33%), in cirrhotics - 10% (range - 40 - 19%; p = 0.40)., Conclusion: HBS showed that hepatic function and volume significantly decreased in parts of the liver treated with 166 Ho-microspheres radioembolization in patients with HCC. Cirrhotic patients do not seem to have the capacity to increase hepatic function in the treated part of the liver., Trial Registration: Registry name: Clinicaltrials.gov., Trial Number: NCT03379844. Date of registration: 21 November 2017. Trial URL: https://clinicaltrials.gov/study/NCT03379844?cond=hcc&term=hepar primary&rank=1#study-overview ., Competing Interests: Declarations. Ethics approval and consent to participate: This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of University Medical Center Utrecht (NEDMEC; NL52338.041.17). Informed consent was obtained from all individual participants included in the study. Consent for publication: Not applicable. Competing interests: MTMR has received non-financial support from Terumo and personal fees from Boston Scientific/BTG, outside the submitted work. MLJS acted as consultant for Boston Scientific/BTG and Terumo, and receives research support from Boston Scientific, outside the submitted work. MGEHL receives grants from Dutch Cancer Society (KWF Kankerbestrijding), research support from Novartis, research support from and consultancy work for Quirem Medical B.V., Terumo and Boston Scientific, outside the submitted work. AJATB is consultant for Terumo and Boston Scientific, and receives research support from Ariceum Therapeutics and Boston Scientific, outside the submitted work. The department of Radiology and Nuclear Medicine of the University Medical Center Utrecht receives royalty payments from Quirem Medical B.V., Terumo, outside the submitted work. The other authors have no relevant financial or non-financial interests to disclose., (© 2025. The Author(s).)

Purpose: To describe the outcome of radiation lobectomy (RL) after double vein embolization (portal vein embolization + hepatic vein embolization) for patients with insufficient future liver remnant growth., Materials and Methods: All patients with insufficient FLR function (as determined by hepatobiliary scintigraphy (HIDA); < 2.7%/min/m 2 ) after double vein embolization who underwent RL between 2020 and 2023 were selected. Follow-up consisted of toxicity graded according to the Common Terminology Criteria for Adverse Events v. 5.0 criteria, HIDA and computed tomography imaging at 1-2-month intervals to assess treatment effect and resectability. Postoperative complications were graded according to the Clavien-Dindo system., Results: Five patients with colorectal liver metastases were selected. After RL, 4/5 patients had sufficient FLR function. Overall, the median volumetric and functional increase of the FLR was 47.5% (range 5.8-102.8%) and 66.7% (range 0-233.3%), respectively, and within a median of 81 days. No severe toxicities were reported after adjunct RL. Two patients did not undergo surgery due to disease progression. Three patients underwent surgery. The postoperative stay was complicated by persistent bile leakage in one patient and respiratory insufficiency in another. There was no 90-day mortality., Conclusion: RL was safely employed in adjunct to double vein embolization to induce a further increase in the FLR volume and function., Competing Interests: Declarations. Conflict of interest: DA, KR, GK and RCGB have nothing to disclose. AJATB has acted as consultant for Boston Scientific, GE Healthcare and Terumo, and receives research support from Ariceum Therapeutics. MGEHL has acted as a consultant for Boston Scientific and Terumo, and receives research support from Novartis, Boston Scientific and Terumo. MLJS has acted as consultant for Terumo, Medtronic and Philips. The UMC Utrecht receives research support and royalties from Terumo and Quiremspheres. All other authors report no conflict of interests., (© 2024. Springer Science+Business Media, LLC, part of Springer Nature and the Cardiovascular and Interventional Radiological Society of Europe (CIRSE).)

Purpose To evaluate the safety and feasibility of a novel hybrid nuclear and fluoroscopy C-arm scanner to be used during the work-up procedure of hepatic radioembolization. Materials and Methods In this prospective first-in-human clinical study, 12 participants (median age, 67 years [range: 37-78 years]; nine [75%] male, three [25%] female) with liver tumors undergoing work-up for yttrium 90 radioembolization were included (ClinicalTrials.gov NCT06013774). Work-up angiography and technetium 99m-macroaggregated albumin injection were performed in an angiography suite equipped with a hybrid C-arm that could simultaneously perform fluoroscopy and planar nuclear imaging. Technetium 99m-macroaggregated albumin was injected under real-time hybrid imaging, followed by in-room SPECT imaging. Safety and feasibility were studied by assessing adverse events, technical performance, additional x-ray radiation dose, and questionnaires completed by radiologists and technologists. Results No adverse events were attributed to the hybrid C-arm scanner. The additional x-ray radiation dose was low (median, 19 Gy · cm 2 ; minimum: 12 Gy · cm 2 ; maximum: 21 Gy · cm 2 for participants who completed all imaging steps). The interventional personnel considered use of the hybrid C-arm scanner safe and feasible, although the additional time spent in the intervention room was considered long (median, 64 minutes; minimum: 55 minutes; maximum: 77 minutes for participants who completed all imaging steps). Conclusion Use of the hybrid C-arm scanner during the work-up procedure of hepatic radioembolization was found to be safe and feasible in this first-in-human clinical study. Keywords: Angiography, Fluoroscopy, Interventional-Vascular, Radionuclide Studies, Radiosurgery, Gamma Knife, Cyberknife, SPECT, Instrumentation, Physics, Technical Aspects, Technology Assessment Supplemental material is available for this article. Published under a CC BY 4.0 license. Clinical trial registration no. NCT06013774.

To date, the imaging and diagnosis of hepatocellular carcinoma (HCC) rely on CT/MRI, which have well-known limitations. Glypican-3 (GPC3) is a cell surface receptor highly expressed by HCC but not by normal or cirrhotic liver tissue. Here we report initial clinical results of GPC3-targeted PET imaging with [ 68 Ga]Ga-DOTA-RYZ-GPC3 (RAYZ-8009), a peptide-based GPC3 ligand in patients with known or suspected HCC. Methods: [ 68 Ga]Ga-RAYZ-8009 was obtained after labeling the peptide precursor with 68 Ga from a 68 Ge/ 68 Ga generator and heating at 90°C for 10 min followed by sterile filtration. After administration of [ 68 Ga]Ga-RAYZ-8009, a dynamic or static PET/CT scan was acquired between 45 min and 4 h after administration. Radiotracer uptake was measured by SUVs for the following tissues: suspected or actual HCC or hepatoblastoma lesions, non-tumor-bearing liver, renal cortex, blood pool in the left ventricle, and gastric fundus. Additionally, tumor-to-healthy-liver ratios (TLRs) were calculated. Results: Twenty-four patients (5 patients in the dynamic protocol; 19 patients in the static protocol) were scanned. No adverse events occurred. Two patients had no lesion detected and did not have HCC during follow-up. In total, 50 lesions were detected and analyzed. The mean SUV max of these lesions was 19.6 (range, 2.7-95.3), and the mean SUV mean was 10.1 (range, 1.0-49.2) at approximately 60 min after administration. Uptake in non-tumor-bearing liver and blood pool rapidly decreased over time and became negligible 45 min after administration (mean SUV mean , <1.6), with a continuous decline to 4 h after administration (mean SUV mean , 1.0). The opposite was observed for HCC lesions, for which SUVs and TLRs continuously increased for up to 4 h after administration. In individual lesion analysis, TLR was the highest between 60 and 120 min after administration. Uptake in the gastric fundus gradually increased for up to 45 min (to an SUV max of 31.3) and decreased gradually afterward. Conclusion: [ 68 Ga]Ga-RAYZ-8009 is safe and allows for high-contrast imaging of GPC3-positive HCC, with rapid clearance from most normal organs. Thereby, [ 68 Ga]Ga-RAYZ-8009 is promising for HCC diagnosis and staging. Further research is warranted., (© 2024 by the Society of Nuclear Medicine and Molecular Imaging.)

Background: Glioblastoma (GBM), the most common malignant brain tumor, is associated with devastating outcomes. IPAX-1 was a multicenter, open-label, single-arm phase I study to evaluate carrier-added 4- L -[ 131 I]iodo-phenylalanine ([ 131 I]IPA) plus external radiation therapy (XRT) in recurrent GBM., Methods: A total of 10 adults with recurrent GBM who had received first-line debulking surgery plus radio-chemotherapy, were randomized to a single-dose regimen (1f; 131 I-IPA 2 GBq before XRT); a fractionated parallel dose regimen (3f-p; 3 131 I-IPA 670 MBq fractions, in parallel with second-line XRT), or a fractionated sequential dose regimen (3f-s; 3 131 I-IPA 670 MBq fractions before and after XRT). Metabolic tumor responses were determined using O-(2-[ 18 F]fluoroethyl)-l-tyrosine positron emission tomography, while single-photon emission computed tomography was used to guide [ 131 I]IPA tumor dosimetry., Results: All dose regimens were well tolerated. Organ-absorbed radiation doses in red marrow (0.38 Gy) and kidney (1.28 Gy) confirmed no radiation-based toxicity. Stable disease was observed in 4 of the 9 patients at 3 months post-treatment (3-month follow-up [FU], 1 patient did not reach protocol-mandated end of study), yielding a response rate of 44.4%. At the 3-month FU, 6 patients demonstrated metabolic stable disease. Median progression-free survival was 4.3 months (95% confidence interval [CI]: 3.3-4.5), while median overall survival was 13 months (95% CI: 7.1-27)., Conclusions: Single or fractionated doses of [ 131 I]IPA plus XRT were associated with acceptable tolerability and specific tumor targeting in patients with recurrent GBM, warranting further investigation., Competing Interests: K. Spiegl, L. Imamovic, A.J.A.T. Braat, J.J.C. Verhoeff, T. Traub-Weidinger and T. Snijders: No competing interests. J. Pichler has received consultant honoraria and research support for performing scientific research from Telix Pharmaceuticals. L. Tauchmanova and C. Hayward are employees of Telix Pharmaceuticals. A. Kluge is founder and shareholder of Telix Pharmaceuticals. TJ Schnijders, JJC Verhoeff: The authors declare that no funds, grants, or other support were received during the preparation of this manuscript., (© The Author(s) 2024. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology.)

Introduction: There is a lack of comprehensive and uniform data on head and neck paragangliomas (HNPGLs), and research is challenging due to its rarity and the involvement of multiple medical specialties. To improve current research data collection, we initiated the Head and Neck Paraganglioma Registry (HNPGL Registry). The aim of the HNPGL Registry is to a) collect extensive data on all HNPGL patients through a predefined protocol, b) give insight in the long term outcomes using patient reported outcome measures (PROMs), c) create uniformity in the diagnostic and clinical management of these conditions, and thereby d) help provide content for future (randomized) research., Methods and Analysis: The HNPGL Registry is designed as a prospective longitudinal observational registry for data collection on HNPGL patients and carriers of (likely) pathogenic variants causative of HNPGLs. All patients, regardless of the received treatment modality, can be included in the registry after informed consent is obtained. All relevant data regarding the initial presentation, diagnostics, treatment, and follow-up will be collected prospectively in an electronic case report form. In addition a survey containing the EuroQol 5D-5L (EQ-5D-5L), European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30), Modified Fatigue Impact Scale (MFIS), Short QUestionnaire to Assess Health-enhancing physical activity (SQUASH), Cancer Worry Scale (CWS) and Hospital Anxiety and Depression Scale (HADS) will be sent periodically. The registry protocol was approved by the Medical Ethical Review Board of the University Medical Center Utrecht., Conclusion: The HNPGL Registry data will be used to further establish the optimal management for HNPGL patients and lay the foundation for guideline recommendations and the outline of future research., Competing Interests: NO authors have competing interests, (Copyright: © 2024 de Bresser et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

This article provides a thorough overview of the practice and multistep approach of hepatic radioembolization. The current literature on hepatic radioembolization in primary or metastatic liver tumors as well as future perspectives are discussed., Competing Interests: Disclosure A.J.A.T. Braat is a consultant for Boston Scientific and Terumo and receives research support from Ariceum Therapeutics. M.L.J. Smits is a consultant for Terumo and has received speaking fees for Medtronic and Philips. G. El-Haddad is a consultant for Boston Scientific, Terumo, Novartis, Bayer, and NorthStar Medical Radioisotopes. M.G.E.H. Lam is a consultant for Boston Scientific and Terumo and receives research support from Novartis, Boston Scientific and Terumo. The UMC Utrecht receives research support and royalties from Terumo., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose: Aim of this study was to investigate a dose-response relationship, dose-toxicity relationship, progression free survival (PFS) and overall survival (OS) in neuroendocrine tumour liver metastases (NELM) treated with holmium-166-microspheres radioembolization ([ 166 Ho]-radioembolization)., Materials and Methods: Single center, retrospective study included patients with NELM that received [ 166 Ho]-radioembolization with post-treatment SPECT/CT and CECT or MRI imaging for 3 months follow-up. Post-treatment SPECT/CT was used to calculate tumour (D t ) and whole liver healthy tissue (D h ) absorbed dose. Clinical and laboratory toxicity was graded by Common Terminology Criteria for Adverse Events (CTCAE), version 5 at baseline and three-months follow-up. Response was determined according to RECIST 1.1. The tumour and healthy doses was correlated to lesion-based objective response and patient-based toxicity. Kaplan Meier analyses were performed for progression free survival (PFS) and overall survival (OS)., Results: Twenty-seven treatments in 25 patients were included, with a total of 114 tumours. Median follow-up was 14 months (3 - 82 months). Mean D t in non-responders was 68 Gy versus 118 Gy in responders, p = 0.01. ROC analysis determined 86 Gy to have the highest sensitivity and specificity, resp. 83% and 81%. Achieving a D t of ≥ 120 Gy provided the highest likelihood of response (90%) for obtaining response. Sixteen patients had grade 1-2 clinical toxicity and only one patient grade 3. No clear healthy liver dose-toxicity relationship was found. The median PFS was 15 months (95% CI [10.2;19.8]) and median OS was not reached., Conclusion: This study confirms the safety and efficacy of [ 166 Ho]-radioembolization in NELM in a real-world setting. A clear dose-response relationship was demonstrated and future studies should aim at a D t of ≥ 120 Gy, being predictive of response. No dose-toxicity relationship could be established., (© 2024. The Author(s).)

Purpose of Review: To provide insights into the role of peptide receptor radionuclide therapy (PRRT) in patients with advanced neuroendocrine tumors (NET) and an overview of possible strategies to combine PRRT with locoregional and systemic anticancer treatments., Recent Findings: Research on combining PRRT with other treatments encompasses a wide variety or treatments, both local (transarterial radioembolization) and systemic therapies, chemotherapy (i.e., capecitabine and temozolomide), targeted therapies (i.e., olaparib, everolimus, and sunitinib), and immunotherapies (e.g., nivolumab and pembrolizumab). Furthermore, PRRT shows promising first results as a treatment prior to surgery. There is great demand to enhance the efficacy of PRRT through combination with other anticancer treatments. While research in this area is currently limited, the field is rapidly evolving with numerous ongoing clinical trials aiming to address this need and explore novel therapeutic combinations., (© 2024. The Author(s).)

Purpose: Radiation pneumonitis is a serious complication of radioembolization. In holmium-166 ([ 166 Ho]) radioembolization, the lung mean dose (LMD) can be estimated (eLMD) using a scout dose with either technetium-99 m-macroaggregated albumin ([ 99m Tc]MAA) or [ 166 Ho]-microspheres. The accuracy of eLMD based on [ 99m Tc]MAA (eLMD MAA ) was compared to eLMD based on [ 166 Ho]-scout dose (eLMD Ho-scout ) in two prospective clinical studies., Materials and Methods: Patients were included if they received both scout doses ([ 99m Tc]MAA and [ 166 Ho]-scout), had a posttreatment [ 166 Ho]-SPECT/CT (gold standard) and were scanned on the same hybrid SPECT/CT system. The correlation between eLMD MAA /eLMD Ho-scout and LMD Ho-treatment was assessed by Spearman's rank correlation coefficient (r). Wilcoxon signed rank test was used to analyze paired data., Results: Thirty-seven patients with unresectable liver metastases were included. During follow-up, none developed symptoms of radiation pneumonitis. Median eLMD MAA (1.53 Gy, range 0.09-21.33 Gy) was significantly higher than median LMD Ho-treatment (0.00 Gy, range 0.00-1.20 Gy; p < 0.01). Median eLMD Ho-scout (median 0.00 Gy, range 0.00-1.21 Gy) was not significantly different compared to LMD Ho-treatment (p > 0.05). In all cases, eLMD MAA was higher than LMD Ho-treatment (p < 0.01). While a significant correlation was found between eLMD Ho-scout and LMD Ho-treatment (r = 0.43, p < 0.01), there was no correlation between eLMD MAA and LMD Ho-treatment (r = 0.02, p = 0.90)., Conclusion: [ 166 Ho]-scout dose is superior in predicting LMD over [ 99m Tc]MAA, in [ 166 Ho]-radioembolization. Consequently, [ 166 Ho]-scout may limit unnecessary patient exclusions and avoid unnecessary therapeutic activity reductions in patients eligible for radioembolization., Trail Registration: NCT01031784, registered December 2009. NCT01612325, registered June 2012., (© 2024. The Author(s).)

Ovarian cancer mortality rates have not decreased significantly in the past years. As most women are still diagnosed in an advanced stage, there is a need for new treatment strategies for recurrent disease. A potentially new developing targeted approach, theranostics, combines diagnostics and treatment using radiopharmaceuticals. Through target receptors, imaging and treatment of malignant tissue can be achieved. For ovarian malignancy, the follicle-stimulating hormone (FSH) receptor may serve as a possible target since expression appears to be limited to ovarian cells. In this systematic review, we aim to gather all available literature on the expression of the FSH receptor in ovarian tumors. Pubmed, Embase and the Cochrane databases were searched until December 2023 for eligible studies. The search yielded 41 studies, mostly regarding serous carcinomas, sex cord-stromal tumors (SCSTs) and cell lines of serous and SCSTs. Various techniques were used to analyze the expression of the FSH receptor. For serous carcinomas, conflicting results on the expression of the FSH receptor were found. Studies on SCSTs, mainly studying the subtype of granulosa cell tumors, all showed positive expression of the FSH receptor. In the cell lines studies, the KGN cell line derived from a granulosa cell tumor shows positive expression in all studies. Available studies show that SCSTs express the FSH receptor. A theranostic approach targeting the FSH receptor may, therefore, provide a useful new approach for this malignancy with limited therapeutic options in recurrent disease.

Purpose: Peptide receptor radionuclide therapy (PRRT) using [ 177 Lu]Lu-DOTATATE has been shown to effectively prolong progression free survival in grade 1-2 gastroenteropancreatic neuroendocrine tumours (GEP-NET), but is less efficacious in patients with extensive liver metastases. The aim was to investigate whether tumour uptake in liver metastases can be enhanced by intra-arterial administration of [ 177 Lu]Lu-DOTATATE into the hepatic artery, in order to improve tumour response without increasing toxicity., Methods: Twenty-seven patients with grade 1-2 GEP-NET, and bi-lobar liver metastases were randomized to receive intra-arterial PRRT in the left or right liver lobe for four consecutive cycles. The contralateral liver lobe and extrahepatic disease were treated via a "second-pass" effect and the contralateral lobe was used as the control lobe. Up to three metastases (> 3 cm) per liver lobe were identified as target lesions at baseline on contrast-enhanced CT. The primary endpoint was the tumour-to-non-tumour (T/N) uptake ratio on the 24 h post-treatment [ 177 Lu]Lu-SPECT/CT after the first cycle. This was calculated for each target lesion in both lobes using the mean uptake. T/N ratios in both lobes were compared using paired-samples t-test., Findings: After the first cycle, a non-significant difference in T/N uptake ratio was observed: T/N IA  = 17·4 vs. T/N control  = 16·2 (p = 0·299). The mean increase in T/N was 17% (1·17; 95% CI [1·00; 1·37]). Of all patients, 67% (18/27) showed any increase in T/N ratio after the first cycle., Conclusion: Intra-arterial [ 177 Lu]Lu-DOTATATE is safe, but does not lead to a clinically significant increase in tumour uptake., (© 2023. The Author(s).)

The Dutch guideline for patients suspected of head and neck paragangliomas (HNPGLs) recommends magnetic resonance imaging (MRI) and/or computed tomography (CT) of the head and neck area. Additionally, it suggests considering additional nuclear imaging. The aim of this study was to evaluate the outcomes of [ 68 Ga]Ga-DOTATOC PET/CT compared to MRI in patients with suspected HNPGLs and carriers of genetic variations., Methods: In this single-center pilot study, retrospective data were obtained from consecutive patients between 2016 and 2023. Both MRI and [ 68 Ga]Ga-DOTATOC PET/CT were performed within 12 months. The primary outcome was the location of HNPGLs., Results: A total of 25 consecutive patients were included, and 7 patients (28.0%, p = 0.5) showed differences between the imaging modalities, of whom 5 patients had unexpected localizations with additional uptake by somatostatin receptors (SSTR) on the [ 68 Ga]Ga-DOTATOC PET/CT., Conclusions: The authors recommend performing baseline imaging with [ 68 Ga]Ga-DOTATOC PET/CT (if available) in variant carriers and using MRI/CT for follow-up according to the regional protocol, thereby shifting the gold standard for baseline imaging from MRI/CT to [ 68 Ga]Ga-DOTATOC PET/CT.

Our objective was to compare 3 different therapeutic particles used for radioembolization in locally advanced intrahepatic cholangiocarcinoma. Methods: 90 Y-glass, 90 Y-resin, and 166 Ho-labeled poly(l-lactic acid) microsphere prescribed activity was calculated as per manufacturer recommendations. Posttreatment quantitative 90 Y PET/CT and quantitative 166 Ho SPECT/CT were used to determine tumor-absorbed dose, whole-normal-liver-absorbed dose, treated-normal-liver-absorbed dose, tumor-to-nontumor ratio, lung-absorbed dose, and lung shunt fraction. Response was assessed using RECIST 1.1 and the [ 18 F]FDG PET-based change in total lesion glycolysis. Hepatotoxicity was assessed using the radioembolization-induced liver disease classification. Results: Six 90 Y-glass, 8 90 Y-resin, and 7 166 Ho microsphere patients were included for analysis. The mean administered activity was 2.6 GBq for 90 Y-glass, 1.5 GBq for 90 Y-resin, and 7.0 GBq for 166 Ho microspheres. Tumor-absorbed dose and treated-normal-liver-absorbed dose were significantly higher for 90 Y-glass than for 90 Y-resin and 166 Ho microspheres (mean tumor-absorbed dose, 197 Gy for 90 Y-glass vs. 73 Gy for 90 Y-resin and 50 Gy for 166 Ho; mean treated-normal-liver-absorbed dose, 79 Gy for 90 Y-glass vs. 37 Gy for 90 Y-resin and 31 Gy for 166 Ho). The whole-normal-liver-absorbed dose and tumor-to-nontumor ratio did not significantly differ between the particles. All patients had a lung-absorbed dose under 30 Gy and a lung shunt fraction under 20%. The 3 groups showed similar toxicity and response according to RECIST 1.1 and [ 18 F]FDG PET-based total lesion glycolysis changes. Conclusion: The therapeutic particles used for radioembolization differed from each other and showed significant differences in absorbed dose, whereas toxicity and response were similar for all groups. This finding emphasizes the need for separate dose constraints and dose targets for each particle., (© 2024 by the Society of Nuclear Medicine and Molecular Imaging.)

Purpose: Trans-arterial radioembolization is a well-studied tumoricidal treatment for liver malignancies; however, consensus and evidence regarding periprocedural prophylactic medication (PPM) are lacking., Methods: A single-center retrospective analysis from 2014 to 2020 was performed in patients treated with 90 Y-glass microspheres for neuroendocrine or colorectal liver metastases. Inclusion criteria were the availability of at least 3 months of clinical, biochemical, and imaging follow-up and post-treatment 90 Y-PET/CT imaging for the determination of the whole non-tumorous liver absorbed dose (D h ). Logistic regression models were used to investigate if variables (among which are P/UDCA and D h ) were associated with either clinical toxicity, biochemical toxicity, or hepatotoxicity. Additionally, a structured literature search was performed in November 2022 to identify all publications related to PPM use in radioembolization treatments., Results: Fifty-one patients received P/UDCA as post-treatment medication, while 19 did not. No correlation was found between toxicity and P/UDCA use. D h was associated with biochemical toxicity ( p = 0.05). A literature review resulted in eight relevant articles, including a total of 534 patients, in which no consistent advice regarding PPM was provided., Conclusion: In this single-center, retrospective review, P/UDCA use did not reduce liver toxicity in patients with metastatic liver disease. The whole non-tumorous liver-absorbed dose was the only significant factor for hepatotoxicity. No standardized international guidelines or supporting evidence exist for PPM in radioembolization.

Background: With the introduction of prostate specific membrane antigen (PSMA) PET/CT, the detection rate of prostate cancer metastases has improved significantly, both for primary staging and for biochemical recurrence. EANM/SNMMI guidelines recommend a 60 min time interval between [ 68 Ga]Ga-PSMA administration and acquisition., Purpose: This study evaluates the possibility of a shorter time interval by investigating the dynamic change in image quality measures., Method: We retrospectively analyzed 10 consecutive prostate cancer patients who underwent a dynamic whole body [ 68 Ga]Ga-PSMA-11 PET/CT of 75 min from skull vertex to mid-thigh using Siemens FlowMotion. PET images were acquired directly after injection of 1.5 MBq/kg [ 68 Ga]Ga-PSMA-11. Image quality measures included lesion maximum standardized uptake value corrected for lean body mass (SUL max ), tumor-to-background ratio (TBR), and contrast-to-noise ratio (CNR). Quantitative analysis of image quality in dynamic PET was performed using PMOD (version 4.2). Regions of interest (ROIs), drawn included different types of prostate lesions (primary tumor, lymph nodes, and bone metastasis), organ tissue (liver, spleen, lacrimal gland, submandibular gland, parotid gland, urinary bladder, kidneys blood pool [ascending aorta], left ventricle), bone tissue (4th lumbar vertebral body [L4]) and muscle tissue (gluteus maximus). To further investigate image quality four 10 min multi-frame reconstructions with clinical parameters were made at different post-injection times (15, 30, 45, and 60 min). A nuclear medicine physician performed a blinded lesion detectability evaluation on these multi-frame reconstructions for different prostate cancer lesions., Results: Six primary prostate tumors in seven patients with prostate in situ, 13 lymph node metastases in six patients and up to 12 bone metastases in three patients were found. The different prostate lesion types (lymph nodes metastases, bone metastases, and primary prostate tumor) all show an increase in average SUL max , TBR, and CNR over time during the scan. The normalized average SUL max , TBR, and CNR of the combined prostate lesions at 15, 30, and 45 min post-injection scans were all significant p < 0.05 lower from the 60 min post-injection [ 68 Ga]Ga-PSMA-11 PET/CT (9.5 ± 4.5, 12.7 ± 6.2, and 41.8 ± 24.5, respectively). At patient level, the reader concluded the same regarding the presence/absence of primary prostate cancer recurrence, lymph node metastases, and/or bone metastases on all <60 min post-injection [ 68 Ga]Ga-PSMA-11 PET/CT's in comparison to the reference scan (60 min post-injection). At lesion level, all bone metastases seen on the reference scan were also seen on all <60 min post-injection [ 68 Ga]Ga-PSMA-11 PET/CT's but there were some lymph nodes (n = 2) metastases missed on the 15, 30, and 45 min post-injection scans. One lymph node metastasis on both the 15 and 30 min post-injection [ 68 Ga]Ga-PSMA-11 PET/CT's was missed and one lymph node metastasis was missed, only on the 45 min post-injection [ 68 Ga]Ga-PSMA-11 PET/CT., Conclusion: Shorter post-injection times (15, 30, and 45 min) compared to the recommended post-injection time of 60 min are not optimal. However, the impact of a shorter time interval of 45 min instead of 60 min between [ 68 Ga]Ga-PSMA-11 administration and the start of PET/CT acquisition on both image quality (SUL max , TBR, and CNR) and lesion detection, while significant, is small., (© 2023 The Authors. Medical Physics published by Wiley Periodicals LLC on behalf of American Association of Physicists in Medicine.)

Objectives: Necrotizing otitis externa (NOE) is a rare infection of the ear that causes osteomyelitis. We aimed to evaluate treatment outcomes and the role of imaging in diagnosing and monitoring disease resolution in a single-center study of patients with NOE., Methods: In this retrospective cohort study, patients with NOE who were diagnosed and treated in a tertiary otology center in Utrecht, The Netherlands, between January 1, 2013 and August 1, 2022, were included. Data were retrieved from the medical records on demographics, symptoms, physical and diagnostic findings, type and duration of treatment, and course of disease., Results: A total of 24 cases were included. Patients were often elderly (mean age = 75 years) and diabetic (88%). Pseudomonas aeruginosa was the most commonly found microorganism (63%). Twenty-two cases (92%) received intravenous antibiotic treatment, and 7 cases (29%) received additional systemic antifungal treatment. The mean duration of systemic treatment was 29 weeks. In 20 out of 22 cases (91%), imaging was used to determine the end point of treatment. None of the cases with a total resolution of disease activity (n = 5) on 18 F-fluorodeoxyglucose-positron emission tomography-computed tomography imaging at the time of cessation of therapy showed clinical relapse, compared with 1 out of 4 cases on gallium single-photon emission computerized tomography., Conclusion: Based on the experience from our center, we demonstrated that patients with NOE can successfully be treated with prolonged systemic treatment. Molecular imaging is reasonably successful for disease evaluation and decision-making on the eradication of disease., Competing Interests: None declared.

Background: Radiation lobectomy is a therapeutic approach that involves targeted radiation delivery to induce future liver remnant hypertrophy and tumor control. In patients with colorectal liver metastases, only 30-40% have complete tumor regression. The importance of tumor biology in treatment response remains elusive., Methods: Patients with colorectal liver metastases who received radiation lobectomy were selected from surgical pathology files. Using a machine learning scoring protocol, pathological response was correlated to tumor absorbed dose and expression of markers of radioresistance Ki-67 (proliferation), CAIX (hypoxia), Olfm4 (cancer stem cells) and CD45 (leukocytes)., Results: No linear association was found between tumor dose and response (ρ < 0.1, P = 0.73 ( 90 Y), P = 0.92 ( 166 Ho)). Response did correlate with proliferation (ρ = 0.56, P = 0.012), and non-responsive lesions had large pools (>15%) of Olfm4 positive cancer stem cells (Fisher's exact test, P = 0.0037). Responding lesions (regression grade ≤2) were highly hypoxic compared to moderate and non-responding lesions (P = 0.011). Non-responsive lesions had more tumor-infiltrating leukocytes (3240 cells/mm 2 versus 650 cells/mm 2 ), although this difference was not significant (P = 0.08)., Conclusion: The aggressive phenotype of a subset of surviving cancer cells emphasizes the importance of prompt resection after radiation lobectomy., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Liver malignancy, including primary liver cancer and metastatic liver cancer, has become one of the most common causes of cancer-related death worldwide due to the high malignant degree and limited systematic treatment strategy. Radioembolization with yttrium-90 ( 90 Y)-loaded microspheres is a relatively novel technology that has made significant progress in the local treatment of liver malignancy. The different steps in the extensive work-up of radioembolization for patients with an indication for treatment with 90 Y microspheres, from patient selection to follow up, both technically and clinically, are discussed in this paper. It describes the application and development of 90 Y microspheres in the treatment of liver cancer., Competing Interests: Feng Duan is the youth editorial board member for Journal of Interventional Medicine and was not involved in the editorial review or the decision to publish this article. All authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 Shanghai Journal of Interventional Radiology Press. Publishing services by Elsevier B.V. on behalf of KeAi Communications Co. Ltd.)

Background: High dose unilobar radioembolization (also termed 'radiation lobectomy')-the transarterial unilobar infusion of radioactive microspheres as a means of controlling tumour growth while concomitantly inducing future liver remnant hypertrophy-has recently gained interest as induction strategy for surgical resection. Prospective studies on the safety and efficacy of the unilobar radioembolization-surgery treatment algorithm are lacking. The RALLY study aims to assess the safety and toxicity profile of holmium-166 unilobar radioembolization in patients with hepatocellular carcinoma ineligible for surgery due to insufficiency of the future liver remnant., Methods: The RALLY study is a multicenter, interventional, non-randomized, open-label, non-comparative safety study. Patients with hepatocellular carcinoma who are considered ineligible for surgery due to insufficiency of the future liver remnant (< 2.7%/min/m 2 on hepatobiliary iminodiacetic acid scan will be included. A classical 3 + 3 dose escalation model will be used, enrolling three to six patients in each cohort. The primary objective is to determine the maximum tolerated treated non-tumourous liver-absorbed dose (cohorts of 50, 60, 70 and 80 Gy). Secondary objectives are to evaluate dose-response relationships, to establish the safety and feasibility of surgical resection following unilobar radioembolization, to assess quality of life, and to generate a biobank., Discussion: This will be the first clinical study to assess the unilobar radioembolization-surgery treatment algorithm and may serve as a stepping stone towards its implementation in routine clinical practice., Trial Registration: Netherlands Trial Register NL8902 , registered on 2020-09-15., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: For safe and effective holmium-166 ( 166 Ho) liver radioembolization, dosimetry is crucial and requires accurate healthy liver definition. The current clinical standard relies on manual segmentation and registration of a separately acquired contrast enhanced CT (CECT), a prone-to-error and time-consuming task. An alternative is offered by simultaneous imaging of 166 Ho and technetium-99m stannous-phytate accumulating in healthy liver cells ( 166 Ho- 99m Tc dual-isotope protocol). This study compares healthy liver segmentation performed with an automatic method using 99m Tc images derived from a 166 Ho- 99m Tc dual-isotope acquisition to the manual segmentation, focusing on healthy liver dosimetry and corresponding hepatotoxicity. Data from the prospective HEPAR PLuS study were used. Automatic healthy liver segmentation was obtained by thresholding the 99m Tc image (no registration step required). Manual segmentation was performed on CECT and then manually registered to the SPECT/CT and subsequently to the corresponding 166 Ho SPECT to compute absorbed dose in healthy liver., Results: Thirty-one patients (66 procedures) were assessed. Manual segmentation and registration took a median of 30 min per patient, while automatic segmentation was instantaneous. Mean ± standard deviation of healthy liver absorbed dose was 18 ± 7 Gy and 20 ± 8 Gy for manual and automatic segmentations, respectively. Mean difference ± coefficient of reproducibility between healthy liver absorbed doses using the automatic versus manual segmentation was 2 ± 6 Gy. No correlation was found between mean absorbed dose in the healthy liver and hepatotoxicity., Conclusions: 166 Ho- 99m Tc dual-isotope protocol can automatically segment the healthy liver without hampering the 166 Ho dosimetry assessment., Trial Registration: ClinicalTrials.gov, NCT02067988. Registered 20 February 2014. https://clinicaltrials.gov/ct2/show/NCT02067988., (© 2023. The Author(s).)

Objectives: To evaluate whether a learning curve affects the bilateral sentinel lymph node (SLN) detection in early-stage cervical cancer., Methods: All patients with FIGO (2018) stage IA1-IB2 or IIA1 cervical cancer who had undergone robot-assisted SLN mapping performed with a combination of preoperative technetium-99m nanocolloids (including preoperative imaging) and intraoperative blue dye were retrospectively included. Risk-adjusted cumulative sum (RA-CUSUM) analysis was used to determine if a learning curve based on bilateral SLN detection existed in this cohort., Results: A total of 227 cervical cancer patients were included. In 98.2% of patients (223/227) at least one SLN was detected. The bilateral SLN detection rate was 87.2% (198/227). Except for age (OR 1.06 per year, 95%CI 1.02-1.09), no significant risk factors for non-bilateral SLN detection were found (e.g., prior conization, BMI or FIGO stage). The RA-CUSUM analysis showed no clear learning phase during the first procedures and cumulative bilateral detection rate remained at least 80% during the entire inclusion period., Conclusions: In this single-institution experience, we observed no learning curve affecting robot-assisted SLN mapping using a radiotracer and blue dye in early-stage cervical cancer patients, with stable bilateral detection rates of at least 80% when adhering to a standardized methodology.

Background: Immunotherapy in the form of checkpoint inhibitors has changed the treatment paradigm in oncology. Combining selective internal radiation therapy (SIRT) with immunotherapy has been suggested to potentially improve outcomes in hepatocellular carcinoma (HCC) and metastatic colorectal carcinoma (mCRC). In this systematic review, the authors discuss the current developments and available clinical data regarding the combination of immunotherapy and SIRT in treating hepatic malignancies. Methods: PubMed, Embase, and Cochrane library were systematically searched for eligible studies (adhering to Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines). Original patient studies written in English language with patients with HCC or mCRC who were treated with SIRT and immunotherapy were included. Endpoints evaluated included overall survival (OS), progression-free survival (PFS), and objective response rate (ORR). Results: 1038 publications were screened, from which 1034 publications were excluded. Four studies with a total of 87 patients were included in this systematic review, of which two consisted of mCRC and the other two HCC. All four studies showed no increased toxicities of the combination therapy over known data on monotherapy. One mCRC study reported a median OS of 8 months, while the other mCRC study ended due to futility. Both reported an ORR of 0%. The two HCC studies reported a median OS of 16.5 and 16.2 months. Median PFS was 5.6 and 5.7 months. ORR ranged from 31% to 80%. Conclusion: The combination of SIRT and immunotherapy has been studied in four early-phase studies showing a favorable safety profile. Further studies are necessary to understand the possible synergy and possible benefit of combination therapy.

Rhabdomyosarcoma, although rare, is the most frequent soft tissue sarcoma in children and adolescents. It can present as a mass at nearly any site in the body, with most common presentations in the head and neck, genitourinary tract and extremities. The optimal diagnostic approach and management of rhabdomyosarcoma require a multidisciplinary team with multimodal treatment, including chemotherapy and local therapy. Survival has improved over the last decades; however, further improvement in management is essential with current 5-year overall survival ranging from 35% to 100%, depending on disease and patient characteristics. In the full patient journey, from diagnosis, staging, management to follow-up after therapy, the paediatric radiologist and nuclear physician are essential members of the multidisciplinary team. Recently, guidelines of the European paediatric Soft tissue sarcoma Study Group, the Cooperative Weichteilsarkom Studiengruppe and the Oncology Task Force of the European Society of Paediatric Radiology (ESPR), in an ongoing collaboration with the International Soft-Tissue Sarcoma Database Consortium, provided guidance for high-quality imaging. In this educational paper, given as a lecture during the 2022 postgraduate ESPR course, the multi-disciplinary team of our national paediatric oncology centre presents the journey of two patients with rhabdomyosarcoma and discusses the impact on and considerations for the clinical (paediatric) radiologist and nuclear physician. The key learning points of the guidelines and their implementation in clinical practice are highlighted and up-to-date insights provided for all aspects from clinical suspicion of rhabdomyosarcoma and its differential diagnosis, to biopsy, staging, risk stratification, treatment response assessment and follow-up., (© 2023. The Author(s).)

Background: Prostate cancer patients with locoregional lymph node disease at diagnosis (N1M0) still have a limited prognosis despite the improvements provided by aggressive curative intent multimodal locoregional external beam radiation therapy (EBRT) with systemic androgen deprivation therapy (ADT). Although some patients can be cured and the majority of patients have a long survival, the 5-year biochemical failure rate is currently 29-47%. [ 177 Lu]Lu-PSMA-617 has shown impressive clinical and biochemical responses with low toxicity in salvage setting in metastatic castration-resistant prostate cancer. This study aims to explore the combination of standard EBRT and ADT complemented with a single administration of [ 177 Lu]Lu-PSMA-617 in curative intent treatment for N1M0 prostate cancer. Hypothetically, this combined approach will enhance EBRT to better control macroscopic tumour localizations, and treat undetected microscopic disease locations inside and outside EBRT fields., Methods: The PROQURE-I study is a multicenter prospective phase I study investigating standard of care treatment (7 weeks EBRT and 3 years ADT) complemented with one concurrent cycle (three, six, or nine GBq) of systemic [ 177 Lu]Lu-PSMA-617 administered in week two of EBRT. A maximum of 18 patients with PSMA-positive N1M0 prostate cancer will be included. The tolerability of adding [ 177 Lu]Lu-PSMA-617 will be evaluated using a Bayesian Optimal Interval (BOIN) dose-escalation design. The primary objective is to determine the maximum tolerated dose (MTD) of a single cycle [ 177 Lu]Lu-PSMA-617 when given concurrent with EBRT + ADT, defined as the occurrence of Common Terminology Criteria for Adverse Events (CTCAE) v 5.0 grade three or higher acute toxicity. Secondary objectives include: late toxicity at 6 months, dosimetric assessment, preliminary biochemical efficacy at 6 months, quality of life questionnaires, and pharmacokinetic modelling of [ 177 Lu]Lu-PSMA-617., Discussion: This is the first prospective study to combine EBRT and ADT with [ 177 Lu]Lu-PSMA-617 in treatment naïve men with N1M0 prostate cancer, and thereby explores the novel application of [ 177 Lu]Lu-PSMA-617 in curative intent treatment. It is considered likely that this study will confirm tolerability as the combined toxicity of these treatments is expected to be limited. Increased efficacy is considered likely since both individual treatments have proven high anti-tumour effect as mono-treatments., Trial Registration: ClinicalTrials, NCT05162573 . Registered 7 October 2021., (© 2023. The Author(s).)

Purpose: Meta-[ 18 F]fluorobenzylguanidine ([ 18 F]mFBG) is a positron emission tomography (PET) radiotracer that allows for fast and high-resolution imaging of tumours expressing the norepinephrine transporter. This pilot study investigates the feasibility of [ 18 F]mFBG PET-CT for imaging in neuroblastoma., Methods: In a prospective, single-centre study, we recruited children with neuroblastoma, referred for meta-[ 123 I]iodobenzylguanidine ([ 123 I]mIBG) scanning, consisting of total body planar scintigraphy in combination with single-photon emission computed tomography-CT (SPECT-CT). Within two weeks of [ 123 I]mIBG scanning, total body PET-CTs were performed at 1 h and 2 h after injection of [ 18 F]mFBG (2 MBq/kg). Detected tumour localisations on scan pairs were compared. Soft tissue disease was quantified by number of lesions and skeletal disease by SIOPEN score., Results: Twenty paired [ 123 I]mIBG and [ 18 F]mFBG scans were performed in 14 patients (median age 4.9 years, n = 13 stage 4 disease and n = 1 stage 4S). [ 18 F]mFBG injection was well tolerated and no related adverse events occurred in any of the patients. Mean scan time for [ 18 F]mFBG PET-CT (9.0 min, SD 1.9) was significantly shorter than for [ 123 I]mIBG scanning (84.5 min, SD 10.5), p < 0.01. Most tumour localisations were detected on the 1 h versus 2 h post-injection [ 18 F]mFBG PET-CT. Compared to [ 123 I]mIBG scanning, [ 18 F]mFBG PET-CT detected a higher, equal, and lower number of soft tissue lesions in 40%, 55%, and 5% of scan pairs, respectively, and a higher, equal, and lower SIOPEN score in 55%, 30%, and 15% of scan pairs, respectively. On average, two more soft tissue lesions and a 6-point higher SIOPEN score were detected per patient on [ 18 F]mFBG PET-CT compared to [ 123 I]mIBG scanning., Conclusion: Results of this study demonstrate feasibility of [ 18 F]mFBG PET-CT for neuroblastoma imaging. More neuroblastoma localisations were detected on [ 18 F]mFBG PET-CT compared to [ 123 I]mIBG scanning. [ 18 F]mFBG PET-CT shows promise for future staging and response assessment in neuroblastoma., Trial Registration: Dutch Trial Register NL8152., (© 2022. The Authors.)

PSMA PET/CT is a diagnostic technique for patients with prostate cancer. It makes use of a radioligand that specifically binds to 'prostate specific membrane antigen' (PSMA), expressed by the prostate cancer cells. PSMA PET has proven to be highly effective in prostate cancer diagnostics in both primary staging and re-staging. PSMA PET/CT has a much higher accuracy than traditional CT and skeletal scintigraphy for the detection of metastases, allowing metastases to be detected in an earlier stage. The clinical relevance of the improved detection is now under investigation. Staging with PSMA PET/CT sometimes leads to avoiding surgery because distant metastases are found that were not detected with conventional imaging. In the Netherlands, PSMA PET/CT is now indicated both in primary prostate cancer diagnostics for the detection of metastases and for the detection of biochemical recurrence after prostatectomy or after radiotherapy.

The safety and efficacy of 166 Ho radioembolization was first determined in the HEPAR and HEPAR II studies, which, however, excluded patients with hepatocellular carcinoma (HCC). The aim of this prospective clinical early phase II study was to establish the toxicity profile of 166 Ho radioembolization in patients with measurable, liver-dominant HCC; Barcelona clinic liver cancer stage B or C; a Child-Pugh score of no more than B7; and an Eastern Cooperative Oncology Group performance status of 0-1 without curative treatment options. Methods: The primary endpoint was a rate of unacceptable toxicity defined as grade 3 hyperbilirubinemia (Common Terminology Cancer Adverse Events, version 4.03) in combination with a low albumin or ascites level in the absence of disease progression or treatment-related serious adverse events. Secondary endpoints included overall toxicity, response, survival, change in α-fetoprotein, and quality of life. Thirty-one patients with Barcelona clinic liver cancer stage B (71%) or C (29%) HCC were included, mostly multifocal (87%) or bilobar (55%) disease. Results: Common grade 1 or 2 clinical toxicity included fatigue (71%), back pain (55%), ascites (32%), dyspnea (23%), nausea (23%), and abdominal pain (23%), with no more than 10% grade 3-5 toxicity. Grade 3 laboratory toxicity (>10%) included an aspartate transaminase and γ-glutamyltransferase increase (16%), hyperglycemia (19%), and lymphopenia (29%). Treatment-related unacceptable toxicity occurred in 3 of 31 patients. At 3 mo, 54% of target lesions showed a complete or partial response according to modified RECIST. Median overall survival was 14.9 mo (95% CI, 10.4-24.9 mo). No significant changes in quality of life or pain were observed. Conclusion: The safety of 166 Ho radioembolization was confirmed in HCC, with less than 10% unacceptable toxicity. Efficacy data support further evaluation., (© 2022 by the Society of Nuclear Medicine and Molecular Imaging.)

Since its first suggestion as possible option for liver radioembolization treatment, the therapeutic isotope holmium-166 ( 166 Ho) caught the experts' attention due to its imaging possibilities. Being not only a beta, but also a gamma emitter and a lanthanide, 166 Ho can be imaged using single-photon emission computed tomography and magnetic resonance imaging, respectively. Another advantage of 166 Ho is the possibility to perform the scout and treatment procedure with the same particle. This prospect paves the way to an individualized treatment procedure, gaining more control over dosimetry-based patient selection and treatment planning. In this review, an overview on 166 Ho liver radioembolization will be presented. The current clinical workflow, together with the most relevant clinical findings and the future prospective will be provided., (© 2022. The Author(s).)

Introduction: Nowadays, two predominant methods for detecting sentinel lymph nodes (SLNs) in cervical cancer are in use. The most conventional method is a combination of a radiotracer, technetium-99m ( 99m Tc) and blue dye. More recently, another method for SLN mapping using indocyanine green (ICG) is becoming widely accepted. ICG is a fluorescent dye, visualised intraoperatively with near-infrared (NIR) fluorescence imaging, providing real-time visual navigation. The presumed advantages of ICG over 99m Tc, that is, being cheaper, non-radioactive and logistically more attractive, are only valuable if its detection rate proves to be at least non-inferior. Before omitting the well-functioning and evidence-based combined approach of 99m Tc and blue dye, we aim to provide prospective evidence on the non-inferiority of ICG with NIR fluorescence imaging., Methods and Analysis: We initiated a prospective non-inferiority study with a paired comparison of both SLN methods in a single sample of 101 patients with International Federation of Gynecology and Obstetrics (FIGO) stage IA-IB2 or IIA1 cervical cancer receiving primary surgical treatment. All patients undergo SLN mapping with ICG and NIR fluorescence imaging in adjunct to mapping with 99m Tc (including single photon emission computed tomography with X-ray computed tomography (SPECT/CT)) and blue dye. Surgeons start SLN detection with ICG while being blinded for the preoperative outcome of SPECT/CT to avoid biased detection with ICG. Primary endpoint of this study is bilateral SLN detection rate of both methods (ie, detection of at least one SLN in each hemipelvis). Since we compare strategies for SLN mapping that are already applied in current daily practice for different types of cancer, no additional risks or burdens are expected from these study procedures., Ethics and Dissemination: The current study is approved by the Medical Ethics Research Committee Utrecht (reference number 21-014). Findings arising from this study will be disseminated in peer-reviewed journals, academic conferences and through patient organisations., Trial Registration Number: NL9011 and EudraCT 2020-005134-15., Competing Interests: Competing interests: RPZ is a proctor for robot-assisted surgery in gynaecological oncology on behalf of Intuitive Surgical., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Despite its high specificity, PSMA PET/CT has a moderate to low sensitivity of 40-50% for pelvic lymph node detection, implicating that a negative PSMA PET/CT cannot rule out lymph node metastases. This study investigates a strategy of implementing PSMA PET/CT for initial prostate cancer staging and treatment planning compared to conventional diagnostics. In this PSMA PET/CT strategy, a bilateral extended pelvic lymph node dissection (ePLND) is only performed in case of a negative PSMA PET/CT; in case of a positive scan treatment planning is solely based on PSMA PET/CT results., Method: A decision table and lifetime state transition model were created. Quality-adjusted life years and health care costs were modelled over lifetime., Results: The PSMA PET/CT strategy of treatment planning based on initial staging with [ 68 Ga]Ga-PSMA-11 PET/CT results in cost-savings of €674 and a small loss in quality of life (QoL), 0.011 QALY per patient. The positive effect of [ 68 Ga]Ga-PSMA-11 PET/CT was caused by abandoning both an ePLND and unnecessary treatment in iM1 patients, saving costs and resulting in higher QoL. The negative effect was caused by lower QoL and high costs in the false palliative state, due to pN1 lim patients (≤ 4 pelvic lymph node metastases) being falsely diagnosed as iN1 ext (> 4 pelvic lymph node metastases). These patients received subsequently palliative treatment instead of potentially curative therapy., Conclusion: Initial staging and treatment planning based on [ 68 Ga]Ga-PSMA-11 PET/CT saves cost but results in small QALY loss due to the rate of false positive findings., (© 2022. The Author(s).)

At diagnosis, 21-50% of neuroendocrine tumors already have distant metastases, of which the liver is most commonly affected. Unfortunately, the presence of neuroendocrine liver metastases (NELM) is the most incriminating factor for survival. At NELM diagnosis, 60-70% of patients suffer from bilobar multifocal disease, making them ineligible for surgical resection. With limited systemic options, a clinical need for liver-directed treatments exists. Trans-arterial (bland) embolization, chemoembolization and radioembolization have been increasingly used in the treatment of NELM. In recent years, radioembolization (also known as selective internal radiation therapy) has gained attention due to promising tumor reductive results, limited toxicities and increasing scientific evidence. This review provides basic insights into radioembolization as a technique, a summary of available literature on radioembolization in NELM, and discusses caveats, challenges and new insights when considering radioembolization in NELM.

Earlier studies have mostly identified pre-therapeutic clinical and laboratory parameters for the prediction of treatment response to [177Lu]Lu-PSMA-617 in metastatic castration resistant prostate cancer patients (mCRPC). The current study investigated whether imaging-derived factors on baseline [68Ga]Ga-PSMA-11 PET/CT can potentially predict the response after two cycles of [177Lu]Lu-PSMA-617 treatment, in a lesion- and patient-based analysis in men with mCRPC. Included patients had histologically proven mCRPC and a [68Ga]Ga-PSMA-11 PET/CT before and after two cycles of [177Lu]Lu-PSMA-617 treatment. The imaging-based response was evaluated on lesion-level (standardized uptake value (SUV) reduction) and patient-level (total lesion PSMA (TL-PSMA) reduction). In the lesion-level analysis, a clear relationship was found between SUVpeak/max and the imaging-based response to [68Ga]Ga-PSMA-11 PET/CT (most avid lesion SUVpeak/max ≥ 30% reduction) (p < 0.001), with no significant difference in cut-off values between different sites of metastases (i.e., lymph node, bone or visceral metastasis). In patient-level analysis, baseline PSA and SUVpeak values of most avid metastasis were significantly associated with imaging-based response (TL-PSMA ≥ 30% reduction) (p = 0.019 and p = 0.015). In pre-treatment with [68Ga]Ga-PSMA-11 PET/CT, a clear accumulation-response relationship in lesion-level was found for SUVpeak/max in men with mCRPC receiving two cycles of [177Lu]Lu-PSMA-617 treatment. The SUVpeak of the most avid lesion was the only image-derived factor predictive of the imaging-based response at the patient-level.

Radiation pneumonitis is a rare but possibly fatal side effect of 90 Y radioembolization. It may occur 1-6 mo after therapy, if a significant part of the 90 Y microspheres shunts to the lungs. In current clinical practice, a predicted lung dose greater than 30 Gy is considered a criterion to exclude patients from treatment. However, contrasting findings regarding the occurrence of radiation pneumonitis and lung dose were previously reported in the literature. In this study, the relationship between the lung dose and the eventual occurrence of radiation pneumonitis after 90 Y radioembolization was investigated. Methods: We retrospectively analyzed 317 90 Y liver radioembolization procedures performed during an 8-y period (February 2012 to September 2020). We calculated the predicted lung mean dose (LMD) using 99m Tc-MAA planar scintigraphy (LMD MAA ) acquired during the planning phase and left LMD (LMD Y-90 ) using the 90 Y PET/CT acquired after the treatment. For the lung dose computation, we used the left lung as the representative lung volume, to compensate for scatter from the liver moving in the craniocaudal direction because of breathing and mainly affecting the right lung. Results: In total, 272 patients underwent 90 Y procedures, of which 63% were performed with glass microspheres and 37% with resin microspheres. The median injected activity was 1,974 MBq (range, 242-9,538 MBq). The median LMD MAA was 3.5 Gy (range, 0.2-89.0 Gy). For 14 procedures, LMD MAA was more than 30 Gy. Median LMD Y-90 was 1 Gy (range, 0.0-22.1 Gy). No patients had an LMD Y-90 of more than 30 Gy. Of the 3 patients with an LMD Y-90 of more than 12 Gy, 2 patients (one with an LMD Y-90 of 22.1 Gy and an LMD MAA of 89 Gy; the other with an LMD Y-90 of 17.7 Gy and an LMD MAA of 34.1 Gy) developed radiation pneumonitis and consequently died. The third patient, with an LMD Y-90 of 18.4 Gy (LMD MAA , 29.1 Gy), died 2 mo after treatment, before the imaging evaluation, because of progressive disease. Conclusion: The occurrence of radiation pneumonitis as a consequence of a lung shunt after 90 Y radioembolization is rare (<1%). No radiation pneumonitis developed in patients with a measured LMD Y-90 lower than 12 Gy., (© 2022 by the Society of Nuclear Medicine and Molecular Imaging.)

Background: Minimally invasive radioguided sentinel lymph node (SLN) procedures, increasingly performed with robot-assisted laparoscopy, can benefit from using a drop-in γ-probe instead of the conventional rigid laparoscopic γ-probe. We evaluated the safety and feasibility of a tethered drop-in γ-probe system for SLN detection in patients with early-stage cervical cancer., Methods: Ten patients with FIGO stage IA - IB2 or IIA1 cervical cancer scheduled for robot-assisted laparoscopic SLN procedure were included. All patients underwent preoperative 240 MBq technetium-99m nanocolloid ( 99m Tc) injection and SPECT/CT imaging. Intraoperatively the tethered drop-in γ-probe SENSEI® (Lightpoint Medical Ltd, Chesham, UK) was used for probe guided SLN detection, subsequently confirmed by the standard rigid laparoscopic γ-probe. Sentinel lymph node detection rates and anatomical SLN location were assessed. Surgeon questionnaires were used to assess usability., Results: In all patients at least one SLN was successfully resected under guidance of the drop-in γ-probe (overall detection rate: 100%). Bilateral SLN detection rate with the drop-in γ-probe was 80%. Of the two patients with unilateral SLN detection only, one presented with an atypical SLN location at the aortic bifurcation that was detected only on SPECT/CT. The other patient had failed unilateral 99m Tc uptake. Combined use of preoperative SPECT/CT and drop-in γ-probe resulted in a bilateral detection rate of 90%. Similar to the drop-in γ-probe, overall and bilateral SLN detection rate of the rigid γ-probe was 100% and 80%, respectively. No significant discrepancy existed between the count rate of the drop-in and rigid laparoscopic γ-probe (p = 0.69). In total 21 SLN's were detected with the drop-in γ-probes including all three tumor positive nodes. Because of wristed articulation of the robotic tissue grasper and possibility of autonomous probe control by the surgeon, maneuverability and control with the drop-in γ-probe were highly rated in surgeon questionnaires. No adverse events related to the intervention occurred., Conclusions: Sentinel lymph node detection with a drop-in γ-probe is safe and feasible in patients with early-stage cervical cancer. Use of the drop-in γ-probe enhances maneuverability and surgical autonomy during robot-assisted SLN detection. Trial registration Netherlands Trial Registry, NL9358. Registered 23 March 2021, https://www.trialregister.nl/trial/9358 ., (© 2022. The Author(s).)

Objective: To evaluate the usefulness of [18F]fluorodeoxyglucose (FDG) positron emissive tomography (PET)/CT in patients with low detectable thyroglobulin levels suspicious for persistent or recurrent differentiated thyroid cancer (DTC)., Methods: A retrospective case series study evaluating FDG PET/CT in patients with detectable thyroglobulin (Tg) levels (≥0.20 and <10.00 ng/mL) after initial treatment with total thyroidectomy and I-131 thyroid remnant ablation for pT1-3aN0-1bM0 DTC. Sensitivity, specificity, positive (PPV) and negative predictive value (NPV) of FDG PET/CT were calculated., Results: Twenty-seven patients underwent FDG PET/CT. Median Tg level at FDG PET/CT was 2.00 ng/mL (range 0.30-9.00). FDG PET/CT was positive in 14 patients (51.9%): lesions suspicious for lymph node metastases were depicted in 12 patients, and lung metastases in 2. DTC was confirmed in 13/14 FDG PET/CT-positive patients. In 9/13 patients with a negative FDG PET/CT, DTC was confirmed ≤3 months after FDG PET/CT. The sensitivity, PPV, specificity and NPV were 59.1, 92.9, 80.0 and 30.8%, respectively., Conclusions: This case series shows that FDG PET/CT might be useful to detect persistent or recurrent DTC in patients with low detectable Tg. However, when FDG PET/CT is negative, this does not rule out DTC and further investigations are necessary.

In neuroendocrine neoplasms (NENs), the presence of distant metastases has a severe impact on survival leading to a relevant decrease in the 5-y survival rate. Here, 90 Y radioembolization ( 90 Y RE) might be an important treatment option; however, data to support clinical benefits for 90 Y RE are scarce. Therefore, the purpose of this study was to analyze the use of 90 Y RE in NEN patients with hepatic metastases in an international, multicenter retrospective analysis and assess the potential role of 90 Y RE in a multimodal treatment concept. Methods: In total, 297 angiographic evaluations in NEN patients before 90 Y RE were analyzed. Baseline characteristics and parameters derived from imaging evaluation and 90 Y RE were analyzed. Tumor response was assessed using RECIST 1.1, and survival data were collected. Mean overall survival (OS) between different groups was compared using Kaplan-Meier curves and the log rank test. A P value of less than 0.05 indicated statistical significance. Results: After 90 Y RE, the disease control rate according to RECIST 1.1 was 83.5% after 3 mo and 50.9% after 12 mo. OS in the entire population was 38.9 ± 33.0 mo. High tumor grade ( P < 0.006) and high tumor burden ( P  = 0.001) were both associated with a significant decrease in OS. The presence of extrahepatic metastases ( P = 0.335) and the type of metastatic vascularization pattern ( P = 0.460) had no influence on OS. Patients who received 90 Y RE as second-line therapy had a slightly longer but not statistically significant OS than patients who had 90 Y RE in a salvage setting (44.8 vs. 30.6 mo, P  = 0.078). Hepatic and global progression-free survival after 90 Y RE was significantly decreased in heavily pretreated patients, compared with patients with second-line therapy ( P = 0.011 and P  = 0.010, respectively). Conclusion: 90 Y RE could be an important alternative to peptide receptor radionuclide therapy as second-line treatment in patients with progressive liver-dominant disease pretreated with somatostatin analogs., (© 2022 by the Society of Nuclear Medicine and Molecular Imaging.)

Objective: In cervical cancer, sentinel lymph nodes (SLNs) are processed according to the pathological ultrastaging protocol. According to current guidelines, immunohistochemistry with pancytokeratin antibodies is performed in addition to step sectioning with hematoxylin and eosin (H&E), aiding the detection of low volume disease (micrometastasis and isolated tumor cells (ITC)). We studied the added clinical value, and costs, of routine immunohistochemistry (IHC)., Methods: We retrospectively included all FIGO stage IA-IIA1 cervical cancer patients who had undergone SLN procedures at UMC Utrecht from 2008 to 2020. Pathological data were derived from the Dutch Pathology Registry (PALGA) including SLN tumor status and number of slides stained with IHC., Results: In total 234 cervical cancer patients were included. In the 516 surgically resected SLN specimens, 630 SLNs were discovered by the pathologist. Hereof, 579 SLNs from 211 patients were routinely processed with IHC. IHC identified three patients with micrometastasis and five patients with ITC undetected with H&E staining. Thereby, IHC significantly increased the number of patients with low volume disease from 11 (5.3%) to 19 patients (9.1%) (p = 0.04). To achieve this, 3791 slides were stained with IHC at an estimated additional cost of €94,775. In 1.4% (95% CI 0.3%-4.3%) of patients routine use of IHC adjusted the adjuvant treatment., Conclusions: Routine use of IHC increases detection of low volume disease in cervical cancer SLNs compared to step sectioning with H&E alone by nearly 4%, with an impact on therapeutic strategy-decisions in about 1% of patients. In view of the high associated costs, cost-effectiveness of routine IHC is questionable., Competing Interests: Declaration of Competing Interest RZ is proctor for robot-assisted surgery in gynecological oncology on behalf of Intuitive Surgical Inc. All other authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article. No funding was received., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Partition modeling allows personalized activity calculation for holmium-166 ( 166 Ho) radioembolization. However, it requires the definition of tumor and non-tumorous liver, by segmentation and registration of a separately acquired CT, which is time-consuming and prone to error. A protocol including 166 Ho-scout, for treatment simulation, and technetium-99m ( 99m Tc) stannous phytate for healthy-liver delineation was proposed. This study assessed the accuracy of automatic healthy-liver segmentation using 99m Tc images derived from a phantom experiment. In addition, together with data from a patient study, the effect of different 99m Tc activities on the 166 Ho-scout images was investigated. To reproduce a typical scout procedure, the liver compartment, including two tumors, of an anthropomorphic phantom was filled with 250 MBq of 166 Ho-chloride, with a tumor to non-tumorous liver activity concentration ratio of 10. Eight SPECT/CT scans were acquired, with varying levels of 99m Tc added to the non-tumorous liver compartment (ranging from 25 to 126 MBq). For comparison, forty-two scans were performed in presence of only 99m Tc from 8 to 240 MBq. 99m Tc image quality was assessed by cold-sphere (tumor) contrast recovery coefficients. Automatic healthy-liver segmentation, obtained by thresholding 99m Tc images, was evaluated by recovered volume and Sørensen-Dice index. The impact of 99m Tc on 166 Ho images and the role of the downscatter correction were evaluated on phantom scans and twenty-six patients' scans by considering the reconstructed 166 Ho count density in the healthy-liver., Results: All 99m Tc image reconstructions were found to be independent of the 166 Ho activity present during the acquisition. In addition, cold-sphere contrast recovery coefficients were independent of 99m Tc activity. The segmented healthy-liver volume was recovered fully, independent of 99m Tc activity as well. The reconstructed 166 Ho count density was not influenced by 99m Tc activity, as long as an adequate downscatter correction was applied., Conclusion: The 99m Tc image reconstructions of the phantom scans all performed equally well for the purpose of automatic healthy-liver segmentation, for activities down to 8 MBq. Furthermore, 99m Tc could be injected up to at least 126 MBq without compromising 166 Ho image quality. Clinical trials The clinical study mentioned is registered with Clinicaltrials.gov (NCT02067988) on February 20, 2014., (© 2022. The Author(s).)

Background: In radioembolization, response is achieved through the irradiation and damaging of tumor DNA. For hepatic metastases of neuroendocrine tumors, a dose-response relationship has not been established yet. This study assesses whether increasing tumor-absorbed doses lead to increased response rates., Methods: We included all patients who underwent yttrium-90 ( 90 Y) glass microspheres radioembolization in our center if both pre- and post-treatment contrast-enhanced CT and post-injection PET/CT were available. Up to five hepatic tumors and the healthy hepatic tissue were delineated, and absorbed dose was quantified using post-injection PET/CT. Response was measured according to RECIST 1.1 on patient and tumor level. Linear mixed models were used to study the relationship between absorbed dose and response on tumor level. Logistic regression analysis was used on patient level to study dose-response and hepatic dose-toxicity relationships., Results: A total of 128 tumors in 26 patients (31 procedures) were included in the response analysis. While correcting for confounding by tumor volume, a significant effect of response on dose was found (p = 0.0465). Geometric mean of absorbed dose for responding tumors was 170 Gy, for stable disease 101 Gy, and for progressive disease 67 Gy. No significant dose-toxicity relationship could be identified., Conclusion: In patients with neuroendocrine tumor liver metastases, treated with 90 Y-radioembolization, a clear dose-response relationship was found. We propose to perform 90 Y-radioembolization with an absolute minimum planned tumor-absorbed dose of 150 Gy., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Intravenous 177 Lu-high-affinity (HA)-DOTATATE has shown promising results for the treatment of surgery- and radiotherapy-refractory meningiomas. We aimed to investigate the added value of intraarterial administration. Methods: Patients underwent at least 1 intravenous 177 Lu-HA-DOTATATE treatment first and subsequent intraarterial cycles. Inpatient and intrapatient comparison was based on posttreatment 177 Lu-HA-DOTATATE imaging 24 h after injection. The technical success rate and adverse events were recorded. Results: Four patients provided informed consent. The technical success rate was 100%, and no angiography-related or unexpected adverse events occurred. Intrapatient comparison showed an increased target lesion accumulation on both planar imaging (mean, +220%) and SPECT/CT (mean, +398%) after intraarterial administration, compared with intravenous administration. No unexpected adverse events occurred during follow-up. Conclusion: Intraarterial peptide receptor radionuclide therapy significantly increases tracer accumulation and is a safe and promising improvement for salvage meningioma patients. Future prospective studies on intraarterial peptide receptor radionuclide therapy are needed to determine the gain in efficacy and survival., (© 2022 by the Society of Nuclear Medicine and Molecular Imaging.)