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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. [ABSTRACT FROM AUTHOR]

Purpose: Radiation pneumonitis is a serious complication of radioembolization. In holmium-166 ([166Ho]) radioembolization, the lung mean dose (LMD) can be estimated (eLMD) using a scout dose with either technetium-99 m-macroaggregated albumin ([99mTc]MAA) or [166Ho]-microspheres. The accuracy of eLMD based on [99mTc]MAA (eLMDMAA) was compared to eLMD based on [166Ho]-scout dose (eLMDHo-scout) in two prospective clinical studies. Materials and Methods: Patients were included if they received both scout doses ([99mTc]MAA and [166Ho]-scout), had a posttreatment [166Ho]-SPECT/CT (gold standard) and were scanned on the same hybrid SPECT/CT system. The correlation between eLMDMAA/eLMDHo-scout and LMDHo-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 eLMDMAA (1.53 Gy, range 0.09–21.33 Gy) was significantly higher than median LMDHo-treatment (0.00 Gy, range 0.00–1.20 Gy; p < 0.01). Median eLMDHo-scout (median 0.00 Gy, range 0.00–1.21 Gy) was not significantly different compared to LMDHo-treatment (p > 0.05). In all cases, eLMDMAA was higher than LMDHo-treatment (p < 0.01). While a significant correlation was found between eLMDHo-scout and LMDHo-treatment (r = 0.43, p < 0.01), there was no correlation between eLMDMAA and LMDHo-treatment (r = 0.02, p = 0.90). Conclusion: [166Ho]-scout dose is superior in predicting LMD over [99mTc]MAA, in [166Ho]-radioembolization. Consequently, [166Ho]-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. [ABSTRACT FROM AUTHOR]

Simple Summary: In the past decades, the survival of ovarian malignant tumors has been largely unchanged. Treatment usually consists of a combination of systemic and surgical therapy. However, when recurrence occurs, treatment options are limited. When repeated surgery is no longer possible and chemotherapy is no longer effective, theranostics, a newly developing approach, might be of value. Theranostics will diagnose and destroy malignant tissue by binding radioactive isotopes to targets on malignant cells. To develop this approach, selection and validation of a target is necessary. For the selection of a target in ovarian tumors, the follicle-stimulating hormone (FSH) receptor appears to be suitable because it is primarily expressed in ovarian tissue, and expression is reported in malignant tumors. This review seeks to determine whether the follicle-stimulating hormone receptor is expressed in ovarian tumor types and, therefore, is suitable as a target in a future theranostic approach. 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. [ABSTRACT FROM AUTHOR]

Simple Summary: All patients suspected of having head and neck paragangliomas (HNPGLs) undergo magnetic resonance imaging (MRI) or computed tomography (CT) of the head and neck area as the standard imaging according to the Dutch guidelines. However, a relatively new imaging modality, [68Ga]Ga-DOTATOC PET/CT, has shown promising results in the detection of HNPGLs. In this pilot study, we aimed to compare the results of this new modality with the standard imaging. We compared both techniques in 25 patients at the University Medical Center Utrecht, The Netherlands. Twenty-eight percent of the patients had different outcomes between both modalities. In all cases, additional HNPGLs were identified using the [68Ga]Ga-DOTATOC PET/CT, suggesting the need for further prospective research to validate this finding. If confirmed, this modality could potentially be implemented as the standard of care for HNPGL detection in germline variant carriers. 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 [68Ga]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 [68Ga]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 [68Ga]Ga-DOTATOC PET/CT. Conclusions: The authors recommend performing baseline imaging with [68Ga]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 [68Ga]Ga-DOTATOC PET/CT. [ABSTRACT FROM AUTHOR]

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 90Y-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 90Y-PET/CT imaging for the determination of the whole non-tumorous liver absorbed dose (Dh). Logistic regression models were used to investigate if variables (among which are P/UDCA and Dh) 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. Dh 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. [ABSTRACT FROM AUTHOR]

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 [68Ga]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 [68Ga]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 [68Ga]Ga‐PSMA‐11. Image quality measures included lesion maximum standardized uptake value corrected for lean body mass (SULmax), 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 SULmax, TBR, and CNR over time during the scan. The normalized average SULmax, 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 [68Ga]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 [68Ga]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 [68Ga]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 [68Ga]Ga‐PSMA‐11 PET/CT's was missed and one lymph node metastasis was missed, only on the 45 min post‐injection [68Ga]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 [68Ga]Ga‐PSMA‐11 administration and the start of PET/CT acquisition on both image quality (SULmax, TBR, and CNR) and lesion detection, while significant, is small. [ABSTRACT FROM AUTHOR]

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%. [177Lu]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 [177Lu]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 [177Lu]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 [177Lu]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 [177Lu]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 [177Lu]Lu-PSMA-617. Discussion: This is the first prospective study to combine EBRT and ADT with [177Lu]Lu-PSMA-617 in treatment naïve men with N1M0 prostate cancer, and thereby explores the novel application of [177Lu]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. [ABSTRACT FROM AUTHOR]

Purpose: Meta-[18F]fluorobenzylguanidine ([18F]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 [18F]mFBG PET-CT for imaging in neuroblastoma. Methods: In a prospective, single-centre study, we recruited children with neuroblastoma, referred for meta-[123I]iodobenzylguanidine ([123I]mIBG) scanning, consisting of total body planar scintigraphy in combination with single-photon emission computed tomography-CT (SPECT-CT). Within two weeks of [123I]mIBG scanning, total body PET-CTs were performed at 1 h and 2 h after injection of [18F]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 [123I]mIBG and [18F]mFBG scans were performed in 14 patients (median age 4.9 years, n = 13 stage 4 disease and n = 1 stage 4S). [18F]mFBG injection was well tolerated and no related adverse events occurred in any of the patients. Mean scan time for [18F]mFBG PET-CT (9.0 min, SD 1.9) was significantly shorter than for [123I]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 [18F]mFBG PET-CT. Compared to [123I]mIBG scanning, [18F]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 [18F]mFBG PET-CT compared to [123I]mIBG scanning. Conclusion: Results of this study demonstrate feasibility of [18F]mFBG PET-CT for neuroblastoma imaging. More neuroblastoma localisations were detected on [18F]mFBG PET-CT compared to [123I]mIBG scanning. [18F]mFBG PET-CT shows promise for future staging and response assessment in neuroblastoma. Trial registration: Dutch Trial Register NL8152. [ABSTRACT FROM AUTHOR]

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 [68Ga]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 [68Ga]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 pN1lim patients (≤ 4 pelvic lymph node metastases) being falsely diagnosed as iN1ext (> 4 pelvic lymph node metastases). These patients received subsequently palliative treatment instead of potentially curative therapy. Conclusion: Initial staging and treatment planning based on [68Ga]Ga-PSMA-11 PET/CT saves cost but results in small QALY loss due to the rate of false positive findings. [ABSTRACT FROM AUTHOR]