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Purpose: Few studies have assessed body weight dependency of Standardised Uptake Value (SUV) formulations in paediatric patients. This study aims to compare different SUV formulations measured in reference tissues in paediatric patients and determine which correction method shows the least dependency on body weight., Methods: A single-centre, retrospective analysis of [18F]FDG PET/CT scans was performed. SUV measurements were taken from liver and blood pool using EARL1 reconstructions. SUV measurements were corrected for body weight (SUVBW), lean body mass (LBM) according to James (SUVLBMJames) and Janmahasatian (SUVLBMJanma), and body surface area (BSA) according to DuBois (SUVBSADuBois) and Haycock (SUVBSAHaycock). The coefficient of determination (r 2 ) was used to assess the correlation between SUV and body weight., Results: In total, 461 scans were analysed, including 185 (40%) from female patients. The median age of patients was 12 years (IQR 8-15.5 years). SUVBW exhibited the strongest correlation with body weight, with r 2  = 0.65 for the liver and r 2  = 0.50 for the blood pool. In contrast, SUVBSADuBois and SUVBSAHaycock had the weakest correlation, with r 2  = 0.09 for the liver and r 2  = 0.06 for the blood pool. SUVLBMJames and SUVLBMJanma had moderate correlations, with r 2  = 0.51 and r 2  = 0.44 for the liver and blood pool, respectively, and r 2  = 0.47 and r 2  = 0.42, respectively., Conclusion: In paediatric [18F]FDG PET/CT scans, SUVBW should be avoided due to elevating values in heavier patients. SUVBSA presents the least dependency on body weight and provides the most consistent assessments of metabolic activity., Competing Interests: Declarations. Ethics approval: This is an observational study. The Medical Research Ethics Committee (MREC) NedMec confirmed on 15th November 2022 (reference: 22–949/DB) that no ethical approval was required, and the informed consent procedure was waived for participating patients. Competing interests: The authors have no relevant financial or non-financial interests to disclose., (© 2025. The Author(s).)

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).)

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: 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).)

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.)

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.)

Purpose: The objective of this study was to investigate whether the use of an anti-reflux catheter improves tumor targeting for colorectal cancer patients with unresectable, chemorefractory liver metastases (mCRC) treated with holmium-166 ( 166 Ho)-radioembolization., Materials and Methods: In this perspective, within-patient randomized study, left and right hepatic perfusion territories were randomized between infusion with a Surefire® anti-reflux catheter or a standard microcatheter. The primary outcome was the difference in tumor to non-tumor (T/N) activity distribution. Secondary outcomes included the difference in infusion efficiency, absorbed doses, predictive value of 166 Ho-scout, dose-response relation, and survival., Results: Twenty-one patients were treated in this study (the intended number of patients was 25). The median T/N activity concentration ratio with the use of the anti-reflux catheter was 3.2 (range 0.9-8.7) versus 3.6 (range 0.8-13.3) with a standard microcatheter. There was no difference in infusion efficiency (0.04% vs. 0.03% residual activity for the standard microcatheter and anti-reflux catheter, respectively) (95%CI - 0.05-0.03). No influence of the anti-reflux catheter on the dose-response rate was found. Median overall survival was 7.8 months (95%CI 6-13)., Conclusion: Using a Surefire® anti-reflux catheter did not result in a higher T/N activity concentration ratio in mCRC patients treated with 166 Ho-radioembolization, nor did it result in improved secondary outcomes measures., Trial Registration: clinicaltrials.gov identifier: NCT02208804.

Purpose: As an alternative to technetium-99m-macroaggregated albumin ( 99m Tc-MAA), a scout dose of holmium-166 ( 166 Ho) microspheres can be used prior to 166 Ho-radioembolization. The use of identical particles for pre-treatment and treatment procedures may improve the predictive value of pre-treatment analysis of distribution. The aim of this study was to analyze the agreement between 166 Ho-scout and 166 Ho-therapeutic dose in comparison with the agreement between 99m Tc-MAA and 166 Ho-therapeutic dose., Methods: Two separate scout dose procedures were performed ( 99m Tc-MAA and 166 Ho-scout) before treatment in 53 patients. First, qualitative assessment was performed by two blinded nuclear medicine physicians who visually rated the agreement between the 99m Tc-MAA, 166 Ho-scout, and 166 Ho-therapeutic dose SPECT-scans (i.e., all performed in the same patient) on a 5-point scale. Second, agreement was measured quantitatively by delineating lesions and normal liver on FDG-PET/CT. These volumes of interest (VOIs) were co-registered to the SPECT/CT images. The predicted absorbed doses (based on 99m Tc-MAA and 166 Ho-scout) were compared with the actual absorbed dose on post-treatment SPECT., Results: A total of 23 procedures (71 lesions, 22 patients) were included for analysis. In the qualitative analysis, 166 Ho-scout was superior with a median score of 4 vs. 2.5 for 99m Tc-MAA (p < 0.001). The quantitative analysis showed significantly narrower 95%-limits of agreement for 166 Ho-scout in comparison with 99m Tc-MAA when evaluating lesion absorbed dose (- 90.3 and 105.3 Gy vs. - 164.1 and 197.0 Gy, respectively). Evaluation of normal liver absorbed dose did not show difference in agreement between both scout doses and 166 Ho-therapeutic dose (- 2.9 and 5.5 Gy vs - 3.6 and 4.1 Gy for 99m Tc-MAA and 166 Ho-scout, respectively)., Conclusions: In this study, 166 Ho-scout was shown to have a superior predictive value for intrahepatic distribution in comparison with 99m Tc-MAA.