Kim Francis Andersen

Background/Objectives: Paediatric PET/CT imaging is crucial in oncology but poses significant radiation risks due to children’s higher radiosensitivity and longer post-exposure life expectancy. This study aims to minimize radiation exposure by generating synthetic CT (sCT) images from emission PET data, eliminating the need for attenuation correction (AC) CT scans in paediatric patients. Methods: We utilized a cohort of 128 paediatric patients, resulting in 195 paired PET and CT images. Data were acquired using Siemens Biograph Vision 600 and Long Axial Field-of-View (LAFOV) Siemens Vision Quadra PET/CT scanners. A 3D parameter transferred conditional GAN (PT-cGAN) architecture, pre-trained on adult data, was adapted and trained on the paediatric cohort. The model’s performance was evaluated qualitatively by a nuclear medicine specialist and quantitatively by comparing sCT-derived PET (sPET) with standard PET images. Results: The model demonstrated high qualitative and quantitative performance. Visual inspection showed no significant (19/23) or minor clinically insignificant (4/23) differences in image quality between PET and sPET. Quantitative analysis revealed a mean SUV relative difference of −2.6 ± 5.8% across organs, with a high agreement in lesion overlap (Dice coefficient of 0.92 ± 0.08). The model also performed robustly in low-count settings, maintaining performance with reduced acquisition times. Conclusions: The proposed method effectively reduces radiation exposure in paediatric PET/CT imaging by eliminating the need for AC CT scans. It maintains high diagnostic accuracy and minimises motion-induced artifacts, making it a valuable alternative for clinical application. Further testing in clinical settings is warranted to confirm these findings and enhance patient safety.

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

We performed a systematic evaluation of the diagnostic performance of LAFOV PET/CT with increasing acquisition time. The first 100 oncologic adult patients referred for 3 MBq/kg 2-[18F]fluoro-2-deoxy-D-glucose PET/CT on the Siemens Biograph Vision Quadra were included. A standard imaging protocol of 10 min was used and scans were reconstructed at 30 s, 60 s, 90 s, 180 s, 300 s, and 600 s. Paired comparisons of quantitative image noise, qualitative image quality, lesion detection, and lesion classification were performed. Image noise (n = 50, 34 women) was acceptable according to the current standard of care (coefficient-of-variance_ref < 0.15) after 90 s and improved significantly with increasing acquisition time (P_B < 0.001). The same was seen in observer rankings (P_B < 0.001). Lesion detection (n = 100, 74 women) improved significantly from 30 s to 90 s (P_B < 0.001), 90 s to 180 s (P_B = 0.001), and 90 s to 300 s (P_B = 0.002), while lesion classification improved from 90 s to 180 s (P_B < 0.001), 180 s to 300 s (P_B = 0.021), and 90 s to 300 s (P_B < 0.001). We observed improved image quality, lesion detection, and lesion classification with increasing acquisition time while maintaining a total scan time of less than 5 min, which demonstrates a potential clinical benefit. Based on these results we recommend a standard imaging acquisition protocol for LAFOV PET/CT of minimum 180 s to maximum 300 s after injection of 3 MBq/kg 2-[18F]fluoro-2-deoxy-D-glucose.

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), p68Ga-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.

Primary cardiac tumors are extremely rare, with an incidence of 0.001–0.03%. Twenty-five percent of these tumors are malignant, with sarcomas accounting for approximately 95%. Cardiac intimal sarcoma is the least reported subtype of primary cardiac sarcoma. These endocardial mesenchymal tumors most often arise from great arterial vessels, and are rarely located in the heart. They often present with an aggressive clinical course and have a poor prognosis, with surgical resection with achievement of free margins being the mainstay of treatment. This emphasizes the importance of an early, correct diagnosis and timely intervention. We report a 60-year-old Caucasian male with several former cardiac surgical procedures due to congenital aortic stenosis, presenting with functional mitral stenosis/insufficiency and left ventricular outflow tract obstruction (LVOTO) due to massive masses in the left ventricle and atrium of the heart. Hybrid imaging with 2-deoxy-2-[¹⁸F]fluoro-D-glucose positron emission tomography/computed tomography (2-[¹⁸F]FDG PET/CT) was performed prior to surgery to characterize the intracardiac masses and estimate tumor burden, as well as to identify a potential extracardiac primary malignancy.

Polymyalgia rheumatica (PMR) and large-vessel vasculitis (LVV) are related rheumatic diseases which are occasionally present concomitantly. PMR is characterized by synovitis and bursitis. In LVV, inflammation of the blood vessel wall is seen. Both disorders can be difficult to diagnose since patients often present non-specific symptoms and results of blood tests. The non-specific symptoms cannot always be distinguished from symptoms indicating an occult malignancy. We present a case of PMR and LVV in a Scandinavian man visualized on [¹⁸F]-2-deoxy-D-glucose positron emission tomography/computed tomography (¹⁸F-FDG PET/CT) with the presentation of typically affected sites of joints and arteries and with the same imaging modality ruling out occult malignancy.

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.