This prospective trial investigated extended [¹⁸F]FDG kinetics in lymphoma to provide in-vivo insights into glucose metabolism with potential relevance for staging and risk stratification. Fifteen consecutive, treatment- naïve lymphoma patients (4 Hodgkin, 11 non-Hodgkin) underwent routine whole-body [18F]FDG-PET/CT at 1 h post injection (p.i., injected activity 3.02 ± 0.34 MBq/kg) followed by additional Long Axial Field-Of-View (LAFOV)-PET/CT scans at 3 h and 6 h p.i. (Biograph Vision Quadra®, Siemens Healthineers; acquisition 5/15/30 min). Standardised uptake values (SUV) of lymphoma, benign lymph nodes, organs and reference tissues were quantified and multi time-point kinetics were described using Retention Indices (RI) and linear/quadratic trajectory analyses. Image quality was rated by two blinded readers on a 5-point Likert scale. Image quality remained diagnostic in all datasets. Median Tumour-to-Background Ratio (TBR) increased significantly from 4.1 (1 h p.i.) to 12.5 (3 h p.i.) and 23.9 (6 h p.i.), p < 0.001. High-grade lymphoma exhibited an almost linear SUV rise, whereas low-grade entities followed a parabolic course, peaking at 3 h p.i. Benign lymph nodes demonstrated constant uptake (1 h: 0.9 ± 0.3, 3 h: 0.8 ± 0.5, 6 h: 0.8 ± 0.4). RIs showed a significant increase in [¹⁸F]FDG uptake over time in lymphoma, compared with a decline in benign lymph nodes (1–3 h p.i.: 19.4

Visceral metastases are a significant risk factor and may be the most critical determinant of outcome in patients with metastatic castration-resistant prostate cancer (mCRPC) undergoing [¹⁷⁷Lu]Lu-PSMA RPT. In this monocentric real-world study, we evaluated baseline parameters derived from PET scans prior to RPT in order to identify potential prognostic factors in mCRPC patients with visceral metastases. This retrospective study included 320 men with mCRPC treated with in total 1077 cycles of [177Lu]Lu-PSMA RPT (1–12 cycles/patient). Baseline characteristics, including age, PSA level, Gleason score, metastatic sites, and prior treatments, were evaluated as potential prognostic factors in the overall cohort. 65 patients were diagnosed with visceral metastases. In this subgroup, we analyzed the PET-derived parameters whole body PSMA-positive tumor volume (PSMA-TV), SUVmax, SUVmean, miPSMA expression score and the metastatic pattern of visceral metastases. The estimated median overall survival (OS) for the entire cohort was 15 months. Presence of visceral metastases, Gleason score, and PSA level were significant negative prognostic baseline factors for the entire cohort in the multivariate Cox regression score. The estimated median OS for patients with visceral metastases was 10 months, which was significantly lower than the 16 months observed for patients without visceral metastases. PSMA-TV, miPSMA expression score, and the metastatic pattern were identified as independent prognostic factors in multivariate Cox regression analysis. Patients exhibiting two risk factors or more demonstrated a significantly poorer OS of 4 months compared to patients with a maximum of one risk factor, who showed an OS of 15 months. This study confirmed that visceral metastases represent a major risk factor in patients with mCRPC undergoing [177Lu]Lu-PSMA RPT. Moreover, PSMA-PET-derived parameters assessed prior to RPT enabled the distinction between high-risk and low-risk subgroups among patients with visceral metastases. These prognostic factors may therefore contribute to improved therapy stratification in mCRPC patients with visceral metastases undergoing [177Lu]Lu-PSMA RPT.

Somatostatin receptor (SSTR)-PET is crucial for effective treatment stratification of neuroendocrine neoplasms (NENs). In highly proliferating or poorly differentiated NENs, dual-tracer approaches using additional [18F]FDG PET can effectively identify SSTR-negative disease, usually requiring separate imaging sessions. We evaluated the feasibility of a one-day dual-tracer imaging protocol with a low activity [18F]FDG PET followed by an SSTR-PET using the recently introduced [18F]SiFAlin-TATE tracer in a long axial field-of-view (LAFOV) PET/CT scanner and its implications in patient management. Twenty NEN patients were included in this study. Initially, a low activity [18F]FDG PET was performed (0.5 ± 0.01 MBq/kg; PET scan 60 min p.i.). After 4.2 ± 0.09 h after completion of the [18F]FDG PET, a standard activity of [18F]SiFAlin-TATE was administered (3.0 MBq/kg; PET scan 90 min p.i.). To ensure the quantification accuracy of the second scan, we evaluated the potential impact of residual [18F]FDG activity by segmenting organs with minimal physiological SSTR-tracer uptake, such as the brain and myocardium, and assessing the activity concentrations (ACTs) of tumor lesions. Residual tumor lesion ACTs of [18F]FDG were calculated by factoring fluorine-18 decay, identifying a maximum residual ACT of 15

18F-labelled somatostatin receptor tracers have recently gained popularity due to their better spatial resolution, longer half-life and lower costs compared to 68Ga-labeled tracers. The aim of this study was to evaluate the impact and limitations of reduced administered activities of [18F]SiTATE on image quality, lesion detectability and quantitative PET parameters in a long axial field-of-view (LAFOV) PET/CT scanner. Twenty-four patients with histologically confirmed neuroendocrine tumor, who underwent clinically indicated [18F]SiTATE PET/CT examination (3.0 MBq/kg, 5 min PET scan time) on a Siemens Biograph Vision Quadra LAFOV PET/CT, were included retrospectively in this study. PET list-mode data were rebinned for shorter frame durations to simulate 5 min scans with lower activities of injected radiotracer. A comparison of image reconstruction in high sensitivity (HS) and ultra-high sensitivity mode (UHS) mode was performed. Subjective image quality, noise and lesion detectability of n = 122 lesions were rated using a 5-point Likert scale. The molecular tumor volume (MTV), signal-to-noise ratio (SNR), tumor-to-liver activity concentration ratio (TLR) and standardized uptake values (SUV) were analyzed. Subjective image quality decreased with simulated reduction of injected activity with generally superior ratings in the UHS mode compared to the HS mode. Despite a reduction to 1 MBq/kg of [18F]SiTATE all lesions were still detected while at 0.25 MBq/kg lesion detectability decreased to 70

Patients with metastatic uveal melanoma (UM) have a poor prognosis. While long‐term survival data in cutaneous melanoma (CM) are promising, such data are lacking in UM and long‐term survivors are rare. In cases of metastases, the liver is affected in 90% of cases and is the main determinant of life expectancy. Immune checkpoint inhibitors (ICI) are less effective in UM than in CM. Therefore, liver‐directed therapies are of high relevance. We evaluated a large cohort of UM patients ( n = 167) who had developed liver metastases between 2005 and 2021. We focused on patients who survived 3 years or more from the initial diagnosis of liver metastases and precisely characterized this cohort with regard to systemic therapies (ST) and liver‐specific procedures applied. The last follow‐up (FU) date was October 31, 2024. We identified 33 long‐term survivors, representing 20% of the total cohort. Most patients had additional extrahepatic metastases (23/33; 70%), while 10 patients had liver metastases only. First‐line treatment in the metastatic setting consisted of liver‐directed therapies in most of the cases (27/33; 82%). 90% of the patients had received at least one liver‐specific procedure at any time point during FU and 85% had received ICI at any time point. Response evaluation revealed a high percentage of patients with disease control (DC) after the first ST (17/27; 63%) or first liver‐specific therapy (27/29; 93%), respectively. Notably, all patients with chemosaturation as their first liver‐specific procedure achieved DC. Further data are needed on the combination of liver‐directed therapy and ST, such as ICI or Tebentafusp.

Background: Lymph node metastases (LNM) are rare in early-stage endometrial cancer, but a diagnostic systematic lymphadenectomy (LNE) is often performed to achieve reliable N-staging. Therefore, this prospective study aimed to evaluate the benefit of [18F]-Fluorodeoxyglucose (FDG) PET/MRI complementary to SPECT/CT guided sentinel lymphonodectomy (SLNE) for a less invasive N-staging Methods: 79 patients underwent a whole-body FDG-PET/MRI, SLN mapping with 99mTc-Nanocolloid SPECT/CT and indocyanine green (ICG) fluoroscopy followed by LNE which served as ground truth. Results: FDG-PET/MRI was highly specific in N-staging (97.2%) but revealed limited sensitivity (66.7%) due to missed micrometastases. In contrast, bilateral SLN mapping failed more often in patients with macrometastases. The combination of SLN mapping and FDG-PET/MRI increased the sensitivity from 66.7% to 77.8%. Additional SLN labeling with dye (ICG) revealed a complete SLN mapping in 80% (8/10) of patients with failed or incomplete SLN detection in SPECT/CT, reducing the need for diagnostic systematic LNE up to 87%. FDG-PET/MRI detected para-aortic LNM in three out of four cases and a liver metastasis. Conclusions: The combination of FDG-PET/MRI and SLNE can reduce the need for diagnostic systematic LNE by up to 87%. PET/MRI complements the SLN technique particularly in the detection of para-aortic LNM and occasional distant metastases.

Background: The tumor-associated disialoganglioside GD2 is a bona fide immunotherapy target in neuroblastoma and other childhood tumors, including Ewing sarcoma and osteosarcoma. GD2-targeting antibodies proved to be effective in neuroblastoma and GD2-targeting chimeric antigen receptors (CAR)- expressing T cells as well as natural killer T cells (NKTs) are emerging. However, assessment of intra- and intertumoral heterogeneity has been complicated by ineffective immunohistochemistry as well as sampling bias in disseminated disease. Therefore, a non-invasive approach for the assessment and visualization of GD2 expression in-vivo is of upmost interest and might enable a more appropriate treatment stratification. Methods: Recently, [64Cu]Cu-NOTA-ch14.18/CHO (64Cu-GD2), a radiolabeled GD2-antibody for imaging with Positron-Emission-Tomography (PET) was developed. We here report our first clinical patients' series (n = 11) in different pediatric tumors assessed with 64Cu-GD2 PET/MRI. GD2-expression in tumors and tissue uptake in organs was evaluated by semiquantitative measurements of standardized uptake values (SUV) with PET/MRI on day 1 p.i. (n = 11) as well as on day 2 p.i. (n = 6). Results: In 8 of 9 patients with suspicious tumor lesions on PET/MRI at least one metastasis showed an increased 64Cu-GD2 uptake and a high tracer uptake (SUVmax > 10) was measured in 4 of those 8 patients. Of note, sufficient image quality with high tumor to background contrast was readily achieved on day 1. In case of 64Cu-GD2-positive lesions, an excellent tumor to background ratio (at least 6:1) was observed in bones, muscles or lungs, while lower tumor to background contrast was seen in the spleen, liver and kidneys. Furthermore, we demonstrated extensive tumor heterogeneity between patients as well as among different metastatic sites in individual patients. Dosimetry assessment revealed a whole-body dose of only 0.03 mGy/MBq (range 0.02-0.04). Conclusion: 64Cu-GD2 PET/MRI enables the non-invasive assessment of individual heterogeneity of GD2 expression, which challenges our current clinical practice of patient selection, stratification and immunotherapy application scheme for treatment with anti-GD2 directed therapies.

Aim/Introduction: Peptide receptor radionuclide therapy (PRRT) represents a cornerstone of treatment regimens for patients with low proliferative neuroendocrine tumors (NETs). However, in patients experiencing somatostatin receptor-positive NET with higher proliferation rates, a value and potential therapeutic benefit of PRRT as part of multimodal treatment approaches and potentially with addition of radiosensitizing agents has not yet been established. Patients and Methods: In this study, 20 patients with histologically confirmed gastroenteropancreatic (GEP) NET with proliferation rates (Ki67) between 15% and 55% were treated either with PRRT only (n = 10) or with a combination therapy (n = 10) comprising PRRT and capecitabine/temozolomide (CAP/TEM) for at least 2 consecutive cycles. Results: Disease control rate in patients treated with PRRT alone was 60% (40% stable disease and 20% partial response). Strikingly, in patients treated with PRRT in combination with radiosensitization (CAP/TEM), the disease control rate was 90% (20% stable disease and 70% partial response). The median progression-free survival in the PRRT only group was 12 months, whereas the median progression-free survival in the PRRT + CAP/TEM group was 26 months and has not been yet reached for all patients in the group during the observation period. The median disease-specific survival for patients with PRRT alone was 51 months, whereas this end point was not yet reached in the PRRT + CAP/TEM group. Moreover, the PRRT + CAP/TEM group showed a significantly higher reduction of SSTR-PET-based metabolic tumor volume and chromogranin A levels compared with the PRRT only group. Importantly, adverse events of all grades did not differ between both groups. Conclusions: PRRT + CAP/TEM represents a highly promising and well-tolerated therapeutic regimen for patients experiencing somatostatin receptor-positive NET with higher (Ki67 >= 15%) proliferation rate. Prospective randomized clinical trials are warranted. [GRAPHICS] .

Purpose: To investigate the impact of [18F]FDG-PET/CT on the management of differentiated thyroid carcinoma (DTC) in routine clinical settings. Material and methods: In total, 98 patients (55 females, age 56 ± 18 years) with histologically confirmed thyroid cancer, including all types of DTC and poorly differentiated thyroid cancer (PDTC, n = 7), underwent [18F]FDG-PET/CT for staging or recurrence diagnostics performed using a state-of-the art clinical scanner (Biograph mCT, Siemens Healthineers) with a standardized examination protocol. The impact of PET/CT on clinical decision making was prospectively evaluated using standardized questionnaires completed by the referring physicians before and after PET/CT. Patient outcome was analyzed for OS drawn from patient records. Results: Referring physicians were unable to establish a treatment plan for 81% of patients with thyroid cancer in the absence of PET/CT. The use of PET/CT had a notable influence on patient management, leading to the development of a well-defined treatment plan for 92% of patients. Moreover, after PET/CT a change in pre-PET/CT-intended treatments occurred in 32% of cases, and further invasive diagnostic could be waived in 7% of cases. [18F]FDG-PET/CT revealed a tumor detection rate of 68% (local tumor: 19%, lymph node metastases: 40%, distant metastases: 42%). HTg levels, when stimulated via TSH, were considerably higher in patients with metastases detected on PET/CT, compared to those without metastatic findings (p = 0.02). OS was significantly worse in patients with PDTC (p = 0.002) compared to follicular thyroid cancer (FTC) and PTC or even in patients with distant metastases at first diagnosis (p = 0.03). Conclusions: This prospective registry study confirms that [18F]FDG-PET/CT used in a routine clinical setting has a very important impact on the management of patients with thyroid cancer by initiating treatments and reducing the uses of additional imaging and invasive tests.

Background: Uveal melanoma is the most common malignant tumor of the eye in adults. About half of the patients develop distant metastases, most commonly liver metastases (>90%). These are associated with poorer overall survival compared to patients with extrahepatic metastases. Patients and methods: In this retrospective study, patients diagnosed with metastatic uveal melanoma between January 2005 and December 2021 and treated at the Center for Dermato-oncology at the University of Tübingen, were included. The total cohort was divided into two groups. Group 1, in which the first diagnosis of metastasis was between 2005 and 2015 and group 2 with first metastasis between 2016 and 2021. Melanoma-specific survival (MSS) and progression-free survival (PFS) were calculated with the Kaplan-Meier method, test for differences was performed by the log-rank test. Results: A total of 167 patients were included in the study. Since more than 90% of patients had developed liver metastases as their first site of metastasis, we focused our analysis on patients with liver metastases. Median MSS was 28 months (95% confidence interval (CI) (22.8–33.2 months)) in patients receiving first-line liver-directed therapy ( n = 89) compared to 10 months (95% CI (8.4–11.6 months)) for patients with first-line systemic therapy ( n = 45). The best MSS was found in patients of group 2 and liver-directed therapy as first-line treatment. Since survival with first-line liver-directed therapy was significantly better in group 2, subsequent systemic therapies must also be considered, especially immune checkpoint inhibitors. Conclusion: This analysis revealed that MSS has improved significantly in recent years. In our analysis, first-line liver-directed therapy was associated with improved survival compared to first-line systemic therapy. Further studies are urgently needed, for example, to investigate the combination of immune checkpoint inhibition or tebentafusp with liver-specific procedures from the outset.

SGCs are rare malignancies, accounting for less than 1% of all head and neck cancers [...]

Background/Objectives: This retrospective observational study aimed to investigate the perioperative outcome in Malignant Peripheral Nerve Sheath Tumors (MPNSTs) with and without relation to Neurofibromatosis Type 1 (NF1) and to detect possible influencing factors. Methods: Clinical reports, histopathological evaluations, imaging, and treatment characteristics were reviewed in 35 operated MPNSTs in 33 patients. Possible predictive valuables included disease type, preoperative tumor volume, SUV and MIB-1 proliferation index, resection margins, the presence of metastasis, and whether radio-/chemotherapy was received. Results: Patients with NF1 were younger (mean age: 29 ± 13, 8–54 years) than sporadic cases (mean age: 45 ± 13, 24–67 years) and exhibited significantly larger preoperative tumor volumes (mean 299 vs. 18 cm3, p = 0.048). Most tumors were located in the facial/cervical/neck area (34%, n = 12), followed by the trunk (31%, n = 11), lower extremity (17%, n = 6), upper extremity (14%, n = 5), and intraspinal area (3%, n = 1). NF1-associated MPNSTs appeared predominantly on the trunk (39%) and sporadically in the facial/cervical/neck area (50%). Complete resection was possible in 66% and an improvement in or stability of function was achieved in most cases (motor 69%, sensory 74%), as well as a decrease in pain intensity (63%). NF1-associated MPNSTs exhibited more severe pain scores (median VRS scale 2, p = 0.002) compared to sporadic tumors (median VRS scale 0.5). Sporadic MPNSTs located at the head/facial/brachial plexus and upper extremities exhibited better preoperative functions compared to those on the lower extremities. In 12 cases with available [18F]FDG PET, the mean preoperative SUV (9.8 ± 7.2) positively correlated with the mean maximum MIB-1 index (34 ± 26%, p = 0.005) and the mean preoperative tumor volume (474.7 ± 68.6 cm3, p = 0.047). The overall survival (OS) was significantly longer in tumors with higher resection extents (R0, p = 0.01) and without accompanying metastasis (p = 0.046), and tended to be longer, but not significantly so, in sporadic MPNSTs. In six and seven tumors, with R1/R2 resection margins and present metastasis, respectively, solid or combined neo-/adjuvant radio-/chemotherapy led to a significantly shorter OS (p = 0.014). Conclusions: NF1-associated MPNSTs have larger tumor volumes, higher SUVs and MIB-1 proliferation indices, and a shorter overall survival period. Nevertheless, surgery can improve symptoms, particularly medication-resistant pain, and should also be considered in advanced disease for symptom control/improvement.

Objectives: The purpose of this study was to investigate the imaging characteristics of medication-related osteonecrosis of the jaw (MRONJ) using [18F]fluoride positron emission tomography/computed tomography (PET/CT) and [18F]fluorodeoxyglucose (FDG) PET/magnetic resonance imaging (MRI) for preoperative assessment and to correlate them with microarchitectural and histomorphometric data with respect to clinical findings. Methods: Twelve patients (five female; mean age 75 ± 7.6 yr) with symptomatic MRONJ underwent both scans on the same day, and imaging findings were used to plan surgical interventions for seven patients. Bone tracer uptake was classified as high, medium, or low, and surgical samples were evaluated using Micro-CT and histomorphometric analysis. Results: CT showed medullary sclerosis in all patients, and MRI revealed gadolinium enhancement in four patients. PET imaging revealed remarkably elevated [18F]fluoride uptake and moderately increased [18F]FDG uptake in MRONJ compared to healthy jawbones, with both differences being statistically significant. [18F]fluoride uptake was associated with necrosis, bacteria, and inflammatory tissue. Micro-CT data did not show significant differences, but histomorphometric analysis revealed higher osteocyte and lacunae densities in the high [18F]fluoride uptake group, and more necrotic bone in the medium [18F]fluoride uptake group. Bacteria were observed in all areas. Conclusions: In summary, [18F]fluoride PET accurately identified MRONJ extent, revealing functional changes in jawbone remodeling not visible on CT. [18F]FDG PET showed differences in bone and soft tissue, though less pronounced. This method aids in evaluating disease activity and guiding treatment planning, requiring further research for optimal surgical approaches based on tracer uptake.