Meta-[¹²³I]iodobenzylguanidine ([¹²³I]MIBG) scintigraphy with SPECT/CT is the standard of care for diagnosing and monitoring neuroblastoma. Replacing [¹²³I]MIBG with the new PET tracer meta-[¹⁸F]fluorobenzylguanidine ([¹⁸F]MFBG) and further improving sensitivity and reducing noise in a new long-axial-field-of-view (LAFOV) PET/CT scanner enable increased image quality and a faster acquisition time, allowing examinations to be performed without sedation or general anesthesia (GA). Focusing on feasibility, we present our first experience with [¹⁸F]MFBG LAFOV PET/CT and compare it with [¹²³I]MIBG scintigraphy plus SPECT/CT for imaging in neuroblastoma in children. Methods: A pilot of our prospective, single-center study recruited children with neuroblastoma who were referred for [¹²³I]MIBG scintigraphy with SPECT/CT. Within 1 wk of [¹²³I]MIBG scintigraphy and SPECT/low-dose CT, [¹⁸F]MFBG LAFOV PET/ultra–low-dose CT was performed 1 h after injection (1.5–3 MBq/kg) without sedation or GA, in contrast to the 24-h postinjection interval needed for scanning with [¹²³I]MIBG, the 2- to 2.5-h acquisition time, and the GA often needed in children less than 6 y old. Based on the spirocyclic iodonium-ylide precursor, [¹⁸F]MFBG was produced in a fully automated good manufacturing practice–compliant procedure. We present the feasibility of the study. Results: In the first paired scans of the first 10 children included (5 at diagnosis, 2 during treatment, 2 during surveillance, and 1 at relapse), [¹⁸F]MFBG PET/CT scan showed a higher number of radiotracer-avid lesions in 80% of the cases and an equal number of lesions in 20% of the cases. The SIOPEN score was higher in 50% of the cases, and the Curie score was higher in 70% of the cases. In particular, intraspinal, retroperitoneal lymph node, and bone marrow involvement was diagnosed with much higher precision. None of the children (median age, 1.6 y; range, 0.1–7.9 y) had sedation or GA during the PET procedure, whereas 80% had GA during [¹²³I]MIBG scintigraphy with SPECT/CT. A PET acquisition time of only 2 min without motion artifacts was the data requirement of the 10-min acquisition time for reconstruction to provide a clinically useful image. Conclusion: This pilot study demonstrates the feasibility of performing [¹⁸F]MFBG LAFOV PET/CT for imaging of neuroblastoma. Further, an increased number of radiotracer-avid lesions, an increased SIOPEN score, and an increased Curie score were seen on [¹⁸F]MFBG LAFOV PET/CT compared with [¹²³I]MIBG scintigraphy with SPECT/CT, and GA and sedation was avoided in all patients. Thus, with a 1-d protocol, a significantly shorter scan time, a higher sensitivity, and the avoidance of GA and sedation, [¹⁸F]MFBG LAFOV PET/CT shows promise for future staging and response assessment and may also have a clinical impact on therapeutic decision-making for children with neuroblastoma. Visual Abstract

A fast-track pathway has been established in Denmark to investigate patients with serious nonspecific symptoms and signs of cancer (NSSC), who are not eligible to enter an organ-specific cancer program. The prevalence of cancer in this cohort is approximately 20%. The optimal screening strategy in patients with NSSC remains unknown. The aim of the study was to investigate whether ¹⁸F-FDG PET/CT was superior to CT as an initial imaging modality in patients with NSSC. In a randomized prospective trial, the imaging modalities were compared with regard to diagnostic performance. Methods: Two hundred patients were randomized 1:1 to whole-body ¹⁸F-FDG PET/CT or CT of the thorax and abdomen as the imaging modality. A tentative diagnosis was established after first-line imaging. The final referral diagnosis was adjudicated by the physician, when sufficient data were available. Results: One hundred ninety-seven patients were available for analysis because 3 patients withdrew consent before scanning. Thirty-nine (20%) patients were diagnosed with cancer, 10 (5%) with an infection, 15 (8%) with an autoimmune disease, and 76 (39%) with other diseases. In the remaining 57 patients (28%), no specific disease was found. ¹⁸F-FDG PET/CT had a higher specificity (96% vs. 85%; P = 0.028) and a higher accuracy (94% vs. 82%; P = 0.017) than CT. However, there were no statistically significant differences in sensitivity (83% vs. 70%) or negative predictive values (96% vs. 92%). No difference in days to final referral diagnosis according to randomization group could be shown (7.2 vs. 7.6 d). However, for the subgroups in which the imaging modality showed a suggestion of malignancy, there was a significant delay to final diagnosis in the CT group compared with the ¹⁸F-FDG PET/CT group (11.6 vs. 5.7 d; P = 0.02). Conclusion: Compared with CT, we found a higher diagnostic specificity and accuracy of ¹⁸F-FDG PET/CT for detecting cancer in patients with NSSC. ¹⁸F-FDG PET/CT should therefore be considered as first-line imaging in this group of patients.

To assess the prognostic value of primary tumor metabolic activity in patients with high-grade bone sarcomas (BS) or soft tissue sarcomas (STS) using F-18 FDG PET/CT. A single-site, retrospective study including 92 patients with high-grade BS or STS. Pretreatment F-18 FDG PET/CT scan was performed. Clinical data were registered. Accuracy of maximum standardized uptake value of primary tumor (SUVmax) and tumor-to-background (T/B) uptake ratio as prognostic variables and identification of cut-off values to group patients were determined. Kaplan-Meier survival estimates and log-rank test were used to compare survival distributions. Prognostic variables were assessed using Cox proportional hazards regression analysis. Forty-one of 92 patients died during follow-up (45%). Average survival was 6.5 years (95% CI 5.8-7.3 years) and probability of 5-year survival was 52%. Accuracy of SUVmax and T/B uptake ratio as prognostic variables in all patients and during subgroup analysis of patients with STS was significant. No significant results for AUCs were registered in patients with BS. Surgery was independently prognostic for survival throughout multivariate regression analysis of all patients (P = 0.001, HR 3.84) and subgroup analysis (BS: P = 0.02, HR 11.62; STS: P = 0.005, HR 4.13). SUVmax was significant as prognostic variable in all patients (P = 0.02, HR 3.66) and in patients with STS (P = 0.007, HR 3.75). No significant results were demonstrated for T/B uptake ratio. Estimation of primary tumor metabolic activity with pretherapeutic SUVmax using F-18 FDG PET/CT demonstrates independent properties beyond histologic grading for prediction of survival in patients with high-grade STS, but not with high-grade BS.

The combined use of Positron Emission Tomography (PET) and Computed Tomography (CT) has become increasingly vital for diagnosing and managing oncological and infectious diseases in pediatric patients. The introduction of long axial field-of-view (LAFOV) PET/CT scanners, also known as "Total Body PET/CT," marks a significant advancement in nuclear medicine. This new technology enables faster pediatric imaging with substantially reduced radiation exposure and essentially eliminates the need for sedation, addressing previous critical concerns in pediatric imaging. This review will explore the applications and challenges of LAFOV PET/CT in pediatric imaging, highlight the benefits observed at two Danish hospitals, and evaluate its potential to transform the management of pediatric patients.

Purpose: The aim of this phase II trial (NCT02965001) was to evaluate the prognostic value of urokinase-type plasminogen activator receptor (uPAR)-PET/CT with the novel ligand ⁶⁸Ga-NOTA-AE105 in head and neck cancer and compare it to ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG). Materials and Methods: Patients with head and neck squamous cell carcinoma (HNSCC) referred to curatively intended radiotherapy were eligible and prospectively included in this phase II study. A ⁶⁸Ga-uPAR- and ¹⁸F-FDG-PET/CT were performed before initiation of curatively intended radiotherapy and maximum standardized uptake values (SUV_max) of the primary tumor was measured on both PET/CTs by two independent readers. Relapse-free survival (RFS) and overall survival (OS) were calculated and optimal cut-off values were established for ⁶⁸Ga-uPAR- and ¹⁸F-FDG-PET independently and compared using log rank and Kaplan-Meier statistics, and univariate and multivariate analysis in Cox proportional hazards model. Results: A total of 57 patients were included and followed for a median of 33.8 months (range 2.30-47.2). The median SUV_max of the primary tumors were 2.98 (range 1.94-5.24) for ⁶⁸Ga-uPAR and 15.7 (range 4.24-45.5) for ¹⁸F-FDG. The optimal cut-off points for ⁶⁸Ga-NOTA-AE105 SUV_max in the primary tumor was 2.63 for RFS and 2.66 for OS. A high uptake of ⁶⁸Ga-NOTA-AE105 (SUV_max above cut-off) was significantly associated with poor RFS and OS (log-rank P = 0.012 and P = 0.022). ⁶⁸Ga-NOTA-AE105-uptake in the primary tumor was significantly associated with poor RFS in univariate analysis (HR=8.53 (95% confidence interval (CI) 1.12-64.7), P = 0.038) and borderline associated with OS (HR=7.44 (95% CI 0.98-56.4), P = 0.052). For ¹⁸F-FDG-PET, the optimal cut-off points were 22.7 for RFS and 22.9 for OS. ¹⁸F-FDG SUV_max above cut-off was significantly associated with reduced RFS (log-rank P = 0.012) and OS (log-rank P = 0.000). ¹⁸F-FDG-uptake was significantly associated with reduced RFS and OS in univariate analysis (HR=3.27; 95% CI 1.237-8.66), P = 0.017) and (HR=7.10; 95% CI 2.60-19.4), p<0.001). In a multivariate analysis including ⁶⁸Ga-uPAR SUV_max, ¹⁸F-FDG SUV_max, Tumor, Node and Metastasis (TNM) stage and p16 status, only ⁶⁸Ga-uPAR SUV_max remained significant (HR 8.51 (95%CI 1.08-66.9), P = 0.042) for RFS. For OS, only TNM stage and ¹⁸F-FDG remained significant. Conclusion: The current phase II clinical trial showed promising results for the use of ⁶⁸Ga-uPAR-PET SUV_max in the primary tumor to predict RFS in HNSCC patients referred to curatively intended radiotherapy when compared to ¹⁸F-FDG-PET, TNM stage and p16 status. ⁶⁸Ga-uPAR-PET could potentially become valuable for identification of patients suited for de-escalation of treatment and risk stratified follow-up schemes.

Histiocytic sarcoma (HS) is a rare hematopoietic neoplasm derived from non-Langerhans histiocytic cells of the monocyte/macrophage system. With an incidence of 0.17/million individuals and a slight male preference, HS presents with a wide age distribution. Most commonly, it occurs as a primary malignancy. In approximately 25% of the cases a presumed transdifferentiation of a preexisting hematolymphoid disorder can be demonstrated. The clinical presentation varies from a localized solitary mass to severe disseminated disease often with extranodal involvement including skin, soft tissue, the gastrointestinal tract and the hematopoietic system. Systemic symptoms in terms of weight loss, fever and night sweats often occur. The diagnostic work-up of HS is extremely challenging due to the rarity of the disease as well as a wide differential diagnosis in terms of a histologic overlap with diverse mimics. No standardized treatment for HS exists and especially in a disseminated disease the clinical course is overly aggressive with a dismal outcome. The median overall survival from the time of diagnosis is approximately six months. We report a 43-year-old previously healthy Caucasian male admitted to our hospitals with abdominal pain and a feeling of fatigue. We demonstrate both the challenges of a correct diagnosis and an effective treatment as well as the aggressive nature of histiocytic sarcoma.