Changes in tumor-to-blood ratio as a prognostic marker for progression-free survival and overall survival in neuroendocrine tumor patients undergoing PRRT.

BACKGROUND: Historically, patient selection for peptide receptor radionuclide therapy (PRRT) has been performed by virtue of somatostatin receptor scintigraphy (SRS). In recent years, somatostatin receptor positron emission tomography (SSTR-PET) has gradually replaced SRS because of its improved diagnostic capacity, creating an unmet need for SSTR-PET-based selection criteria for PRRT. Tumor-to-blood ratio (TBR) measurements have shown high correlation with the net influx rate Ki, reflecting the tumor somatostatin receptor expression, to a higher degree than standardized uptake value (SUV) measurements. TBR may therefore predict treatment response to PRRT. In addition, changes in semiquantitative SSTR-PET parameters have been shown to predate morphological changes, making them a suitable metric for response assessment. METHODS: The institutional database of the Department of Nuclear Medicine (University Hospital Essen) was searched for NET patients undergoing ≥ 2 PRRT cycles with available baseline and follow-up SSTR-PET. Two blinded independent readers reported the occurrence of new lesions quantified tumor uptake of up to nine lesions per patient using SUV and TBR. The association between baseline TBR and changes in uptake/occurrence of new lesions with progression-free survival (PFS) and overall survival (OS) was tested by use of a Cox regression model and log-rank test. RESULTS: Patients with baseline TBR in the 1st quartile had a shorter PFS (14.4 months) than those in the 3rd (23.7 months; p = 0.03) and 4th (24.1 months; p = 0.02) quartile. Similarly, these patients had significantly shorter OS (32.5 months) than those with baseline TBR in the 2nd (41.8 months; p = 0.03), 3rd (69.2 months; p < 0.01), and 4th (42.7 months; p = 0.03) quartile. Baseline to follow-up increases in TBR were independently associated with shorter PFS when accounting for prognostic markers, e.g., RECIST response (hazard ratio = 2.91 [95%CI = 1.54-5.50]; p = 0.01). This was confirmed with regard to OS (hazard ratio = 1.64 [95%CI = 1.03-2.62]; p = 0.04). Changes in SUVmean were not associated with PFS or OS. CONCLUSIONS: Baseline TBR as well as changes in TBR were significantly associated with PFS and OS and may improve patient selection and morphological response assessment. Future trials need to assess the role of TBR for therapy monitoring also during PRRT and prospectively explore TBR as a predictive marker for patient selection.

Incidental 18F-FDG uptake in the colon: value of contrast-enhanced CT correlation with colonoscopic findings.

OBJECTIVES: To evaluate the impact of morphological information derived from contrast-enhanced CT in the characterization of incidental focal colonic uptake in 18F-FDG PET/CT examinations. METHODS: A total of 125 patients (female: n = 53, male: n = 72) that underwent colonoscopy secondary to contrast-enhanced, full-dose PET/CT without special bowel preparation were included in this retrospective study. PET/CT examinations were assessed for focal colonic tracer uptake in comparison with the background. Focal tracer uptake was correlated with morphological changes of the colonic wall in the contrast-enhanced CT images. Colonoscopy reports were evaluated for benign, inflammatory, polypoid, precancerous, and cancerous lesions verified by histopathology, serving as a reference standard. Sensitivity, specificity, PPV, NPV, and accuracy for detection of therapeutic relevant findings were calculated for (a) sole focal tracer uptake and (b) focal tracer uptake with correlating CT findings in contrast-enhanced CT. RESULTS: In 38.4% (48/125) of the patients, a focal 18F-FDG uptake was observed within 67 lesions. Malignant lesions were endoscopically and histopathologically diagnosed in eleven patients, and nine of these were detected by focal 18F-FDG uptake. A total of 34 lesions with impact on short- or long-term patient management (either being pre- or malignant) were detected. Sensitivity, Specificity, PPV, NPV, and accuracy for sole 18F-FDG uptake for this combined group were 54%, 69%, 29%, 85%, and 65%. Corresponding results for focal 18F-FDG uptake with correlating CT findings were 38%, 90%, 50%, 86%, and 80%. This resulted in a statistically significant difference for diagnostic accuracy (p = 0.0001) CONCLUSION: By analyzing additional morphological changes in contrast-enhanced CT imaging, the specificity of focal colonic 18F-FDG uptake for precancerous and cancerous lesions can be increased but leads to a considerate loss of sensitivity. Therefore, every focal colonic uptake should be followed up by colonoscopy.

Prospective evaluation of whole-body MRI and 18F-FDG PET/MRI in N and M staging of primary breast cancer patients.

OBJECTIVES: To evaluate and compare the diagnostic potential of whole-body MRI and whole-body 18F-FDG PET/MRI for N and M staging in newly diagnosed, histopathologically proven breast cancer. MATERIAL AND METHODS: A total of 104 patients (age 53.4 ± 12.5) with newly diagnosed, histopathologically proven breast cancer were enrolled in this study prospectively. All patients underwent a whole-body 18F-FDG PET/MRI. MRI and 18F-FDG PET/MRI datasets were evaluated separately regarding lesion count, lesion localization, and lesion characterization (malignant/benign) as well as the diagnostic confidence (5-point ordinal scale, 1-5). The N and M stages were assessed according to the eighth edition of the American Joint Committee on Cancer staging manual in MRI datasets alone and in 18F-FDG PET/MRI datasets, respectively. In the majority of lesions histopathology served as the reference standard. The remaining lesions were followed-up by imaging and clinical examination. Separately for nodal-positive and nodal-negative women, a McNemar chi2 test was performed to compare sensitivity and specificity of the N and M stages between 18F-FDG PET/MRI and MRI. Differences in diagnostic confidence scores were assessed by Wilcoxon signed rank test. RESULTS: MRI determined the N stage correctly in 78 of 104 (75%) patients with a sensitivity of 62.3% (95% CI: 0.48-0.75), a specificity of 88.2% (95% CI: 0.76-0.96), a PPV (positive predictive value) of 84.6% % (95% CI: 69.5-0.94), and a NPV (negative predictive value) of 69.2% (95% CI: 0.57-0.8). Corresponding results for 18F-FDG PET/MRI were 87/104 (83.7%), 75.5% (95% CI: 0.62-0.86), 92.2% (0.81-0.98), 90% (0.78-0.97), and 78.3% (0.66-0.88), showing a significantly better sensitivity of 18F-FDG PET/MRI determining malignant lymph nodes (p = 0.008). The M stage was identified correctly in MRI and 18F-FDG PET/MRI in 100 of 104 patients (96.2%). Both modalities correctly staged all 7 patients with distant metastases, leading to false-positive findings in 4 patients in each modality (3.8%). In a lesion-based analysis, 18F-FDG PET/MRI showed a significantly better performance in correctly determining malignant lesions (85.8% vs. 67.1%, difference 18.7% (95% CI: 0.13-0.26), p < 0.0001) and offered a superior diagnostic confidence compared with MRI alone (4.1 ± 0.7 vs. 3.4 ± 0.7, p < 0.0001). CONCLUSION: 18F-FDG PET/MRI has a better diagnostic accuracy for N staging in primary breast cancer patients and provides a significantly higher diagnostic confidence in lesion characterization than MRI alone. But both modalities bear the risk to overestimate the M stage.

Prospective comparison of 18F-FDG PET/MRI and 18F-FDG PET/CT for thoracic staging of non-small cell lung cancer.

OBJECTIVES: To compare the diagnostic performance of 18F-FDG PET/MRI and 18F-FDG PET/CT for primary and locoregional lymph node staging in non-small cell lung cancer (NSCLC). METHODS: In this prospective study, a total of 84 patients (51 men, 33 women, mean age 62.5 ± 9.1 years) with histopathologically confirmed NSCLC underwent 18F-FDG PET/CT followed by 18F-FDG PET/MRI in a single injection protocol. Two readers independently assessed T and N staging in separate sessions according to the seventh edition of the American Joint Committee on Cancer staging manual for 18F-FDG PET/CT and 18F-FDG PET/MRI, respectively. Histopathology as a reference standard was available for N staging in all 84 patients and for T staging in 39 patients. Differences in staging accuracy were assessed by McNemars chi2 test. The maximum standardized uptake value (SUVmax) and longitudinal diameters of primary tumors were correlated using Pearson's coefficients. RESULTS: T stage was categorized concordantly in 18F-FDG PET/MRI and 18F-FDG PET/CT in 38 of 39 (97.4%) patients. Herein, 18F-FDG PET/CT and 18F-FDG PET/MRI correctly determined the T stage in 92.3 and 89.7% of patients, respectively. N stage was categorized concordantly in 83 of 84 patients (98.8%). 18F-FDG PET/CT correctly determined the N stage in 78 of 84 patients (92.9%), while 18F-FDG PET/MRI correctly determined the N stage in 77 of 84 patients (91.7%). Differences between 18F-FDG PET/CT and 18F-FDG PET/MRI in T and N staging accuracy were not statistically significant (p > 0.5, each). Tumor size and SUVmax measurements derived from both imaging modalities exhibited excellent correlation (r = 0.963 and r = 0.901, respectively). CONCLUSION: 18F-FDG PET/MRI and 18F-FDG PET/CT show an equivalently high diagnostic performance for T and N staging in patients suffering from NSCLC.

Prospective comparison of whole-body MRI and 68Ga-PSMA PET/CT for the detection of biochemical recurrence of prostate cancer after radical prostatectomy.

PURPOSE: To assess whole-body magnetic resonance imaging (wb-MRI) for detection of biochemical recurrence in comparison to 68Ga-prostate-specific membrane antigen positron emission tomography/computed tomography (68Ga-PSMA PET/CT) in prostate cancer (Pca) patients after radical prostatectomy. METHODS: This was a prospective trial including 28 consecutive patients (mean age 65.3 ± 9.0 years) with newly documented biochemical recurrence of Pca (mean prostate-specific antigen, PSA, 2.09 ± 1.95 ng/ml) following radical prostatectomy. All patients underwent both wb-MRI including a dedicated pelvic imaging protocol and PET/CT with 166 ± 35 MBq 68Ga-PSMA within a time window of 11 ± 10 days. PET/CT and MRI datasets were separately evaluated regarding Pca lesion count, type, localization and diagnostic confidence (three-point Likert scale, 1-3) by two nuclear medicine specialists and two radiologists, respectively. The reference standard was based on histopathological results, PSA levels following targeted salvage irradiation and follow-up imaging. Lesion-based and patient-based detection rates were compared using the chi-squared test. Differences in diagnostic confidence were assessed using the Welch test. RESULTS: A total of 56 Pca lesions were detected in 20 of the 28 patients. 68Ga-PSMA PET/CT detected 56 of 56 lesions (100%) in 20 patients (71.4%), while wb-MRI detected 13 lesions (23.2%) in 11 patients (39.3%). The higher detection rate with 68Ga-PSMA PET/CT was statistically significant on both a per-lesion basis (p < 0.001) and a per-patient basis (p = 0.0167). In 8 patients (28.6%) no relapse was detectable by either modality. All lesions detected by wb-MRI were also detected by 68Ga-PSMA PET/CT. Additionally, 68Ga-PSMA PET/CT provided superior diagnostic confidence in identifying Pca lesions (2.7 ± 0.7 vs. 2.3 ± 0.6, p = 0.044). CONCLUSION: 68Ga-PSMA PET/CT significantly out-performed wb-MRI in the detection of biochemical recurrence in Pca patients after radical prostatectomy.

Differences of radiocarpal cartilage alterations in arthritis and osteoarthritis using morphological and biochemical magnetic resonance imaging without gadolinium-based contrast agent administration.

OBJECTIVES: To identify differences of radiocarpal cartilage alterations in osteoarthritis and arthritis using multiparametrical magnetic resonance imaging (MRI) comprising morphological and biochemical sequences without gadolinium-based contrast agent administration. METHODS: In this prospective study, multiparametrical MRI of the radiocarpal cartilage was performed in 47 participants (mean age, 46.6 ± 17.6 years; min., 20 years; max., 79 years) on a 3 Tesla MRI. The cohort consisted of 11 patients suffering from arthritis, 10 patients with osteoarthritis, 14 patients after distal radius fracture, and 12 healthy volunteers. The radiocarpal cartilage was assessed using morphological (DESS, TrueFISP) and biochemical (T2*) MRI sequences without the application of intravenous contrast agent. The modified Outerbridge classification system for morphological and region-of-interest analyses for biochemical analysis was applied to assess the degree of cartilage damage in each patient before data were statistically tested for significant difference between the groups using a post hoc Tukey test. RESULTS: In morphological imaging, cartilage damage was significantly more frequent in arthritis and osteoarthritis than in healthy volunteers (DESS: p = 0.01, p = 0.0004; TrueFISP: p = 0.02, p = 0.0001). In T2* imaging, patients with osteoarthritis showed higher cartilage damage compared to patients with arthritis (p = 0.01). CONCLUSION: With multiparametrical MRI, it is possible to identify differences of radiocarpal cartilage alterations of patients with arthritis and osteoarthritis using the combination of morphological and biochemical MR imaging of the radiocarpal cartilage without the application of contrast agent. Multiparametrical MRI without the usage of contrast agent may be a potential tool helping to distinguish both entities. KEY POINTS: • Multiparametrical MRI with morphological and biochemical sequences allows the differentiation of patients with arthritis and osteoarthritis. • High-resolution MRI of radiocarpal cartilage is possible without administration of contrast agent.

Comparison of 18F-FDG PET/MRI and MRI for pre-therapeutic tumor staging of patients with primary cancer of the uterine cervix.

PURPOSE: The aim of the present study was to assess and compare the diagnostic performance of integrated PET/MRI and MRI alone for local tumor evaluation and whole-body tumor staging of primary cervical cancers. In addition, the corresponding impact on further patient management of the two imaging modalities was assessed. METHODS: A total of 53 consecutive patients with histopathological verification of a primary cervical cancer were prospectively enrolled for a whole-body 18F-FDG PET/MRI examination. Two experienced physicians analyzed the MRI data, in consensus, followed by a second reading session of the PET/MRI datasets. The readers were asked to perform a dedicated TNM staging in accordance with the 7th edition of the AJCC staging manual. Subsequently, the results of MRI and PET/MRI were discussed in a simulated interdisciplinary tumor board and therapeutic decisions based on both imaging modalities were recorded. Results from histopathology and cross-sectional imaging follow-up served as the reference standard. RESULTS: PET/MRI allowed for a correct determination of the T stage in 45/53 (85%) cases, while MRI alone enabled a correct identification of the tumor stage in 46/53 (87%) cases. In 24 of the 53 patients, lymph node metastases were present. For the detection of nodal-positive patients, sensitivity, specificity and accuracy of PET/MRI were 83%, 90% and 87%, respectively. The respective values for MRI alone were 71%, 83% and 77%. In addition, PET/MRI showed higher values for the detection of distant metastases than MRI alone (sensitivity: 87% vs. 67%, specificity: 92% vs. 90%, diagnostic accuracy: 91% vs. 83%). Among the patients with discrepant staging results in the two imaging modalities, PET/MRI enabled correct treatment recommendations for a higher number (n = 9) of patients than MRI alone (n = 3). CONCLUSION: The present results demonstrate the successful application of integrated PET/MRI imaging for whole-body tumor staging of cervical cancer patients, enabling improved treatment planning when compared to MRI alone.

Comparison of 18F-FDG PET/MRI and MRI alone for whole-body staging and potential impact on therapeutic management of women with suspected recurrent pelvic cancer: a follow-up study.

PURPOSE: To evaluate the diagnostic performance of 18F-FDG PET/MRI for whole-body staging and potential changes in therapeutic management of women with suspected recurrent pelvic cancer in comparison with MRI alone. METHODS: Seventy-one consecutive women (54 ± 13 years, range: 25-80 years) with suspected recurrence of cervical (32), ovarian (26), endometrial (7), vulvar (4), and vaginal (2) cancer underwent PET/MRI including a diagnostic contrast-enhanced MRI protocol. PET/MRI and MRI datasets were separately evaluated regarding lesion count, localization, categorization (benign/malignant), and diagnostic confidence (3-point scale; 1-3) by two physicians. The reference standard was based on histopathology results and follow-up imaging. Diagnostic accuracy and proportions of malignant and benign lesions rated correctly were retrospectively compared using McNemar's chi2 test. Differences in diagnostic confidence were assessed by Wilcoxon test. RESULTS: Fifty-five patients showed cancer recurrence. PET/MRI correctly identified more patients with cancer recurrence than MRI alone (100% vs. 83.6%, p < 0.01). In contrast to PET/MRI, MRI alone missed 4/15 patients with pelvic recurrence and miscategorized 8/40 patients with distant metastases as having local recurrence only. Based on the reference standard, 241 lesions were detected in the study cohort (181 malignant, 60 benign). While PET/MRI provided correct identification of 181/181 (100%) malignant lesions, MRI alone correctly identified 135/181 (74.6%) malignant lesions, which was significantly less compared to PET/MRI (p < 0.001). PET/MRI offered superior diagnostic accuracy (99.2% vs. 79.3%, p < 0.001) and diagnostic confidence in the categorization of malignant lesions compared with MRI alone (2.7 ± 0.5 vs. 2.4 ± 0.7, p < 0.001). CONCLUSION: PET/MRI demonstrates excellent diagnostic performance and outperforms MRI alone for whole-body staging of women with suspected recurrent pelvic cancer, indicating potential changes in therapy management based on evaluation of local recurrence and distant metastatic spread.

Thoracic staging with 18F-FDG PET/MR in non-small cell lung cancer - does it change therapeutic decisions in comparison to 18F-FDG PET/CT?

OBJECTIVE: To investigate whether differences in thoracic tumour staging between 18F-FDG PET/CT and PET/MR imaging lead to different therapeutic decisions in Non-Small Cell Lung Cancer (NSCLC). MATERIAL AND METHODS: Seventy-seven NSCLC patients that underwent whole-body 18F-FDG PET/CT from the base of skull to the upper thighs and thoracic PET/MR were enrolled in this retrospective study. Thoracic PET/CT and PET/MR images were staged according to the 7th edition of the AJCC staging manual. Staging results of both modalities were discussed separately in a simulated interdisciplinary tumour board and therapeutic decisions based on both imaging modalities were recorded. Descriptive statistics were used to compare the results and reasons for changes in the therapeutic decision were investigated. RESULTS: Staging results differed in 35 % of patients (27 patients) between thoracic PET/CT and PET/MR. Differences were detected when assessing the T-stage in 18 % (n = 14), the N-stage in 23 % (n = 18), and the M-stage in 1 % (n = 1). However, patient therapy management was changed in only six patients (8 %). CONCLUSION: Despite the variability of thoracic 18F-FDG PET/CT and PET/MR in TNM-staging, both modalities lead to comparable therapeutic decisions in patients suffering from NSCLC. Hence, 18F-FDG PET/MR can be considered an possible alternative to 18F-FDG PET/CT for clinical NSCLC staging. KEY POINTS: • PET/CT and PET/MR provide comparable results in early stages in NSCLC • Clinical impact of different staging results has not been investigated • PET/CT and PET/MR lead to comparable therapeutic decisions • PET/MR can be considered an alternative to PET/CT for NSCLC staging.

Impact of CT and MRI in the diagnostic workup of malignant triton tumour-a monocentric analysis and review of the literature.

OBJECTIVES: Malignant triton tumours (MTTs) are rare but aggressive subtypes of malignant peripheral nerve sheath tumours (MPNSTs) with a high recurrence rate and 5-year survival of 14%. Systematic imaging data on MTTs are scarce and mainly based on single case reports. Therefore, we aimed to identify typical CT and MRI features to improve early diagnosis rates of this uncommon entity. METHODS: A systematic review on literature published until December 2022 on imaging characteristics of MTTs was performed. Based on that, we conducted a retrospective, monocentric analysis of patients with histopathologically proven MTTs from our department. Explorative data analysis was performed. RESULTS: Initially, 29 studies on 34 patients (31.42 ± 22.6 years, 12 female) were evaluated: Literature described primary MTTs as huge, lobulated tumours (108 ± 99.3 mm) with central necrosis (56% [19/34]), low T1w (81% [17/21]), high T2w signal (90% [19/21]) and inhomogeneous enhancement on MRI (54% [7/13]). Analysis of 16 patients (48.9 ± 13.8 years; 9 female) from our institution revealed comparable results: primary MTTs showed large, lobulated masses (118 mm ± 64.9) with necrotic areas (92% [11/12]). MRI revealed low T1w (100% [7/7]), high T2w signal (100% [7/7]) and inhomogeneous enhancement (86% [6/7]). Local recurrences and soft-tissue metastases mimicked these features, while nonsoft-tissue metastases appeared unspecific. CONCLUSIONS: MTTs show characteristic features on CT and MRI. However, these do not allow a reliable differentiation between MTTs and other MPNSTs based on imaging alone. Therefore, additional histopathological analysis is required. ADVANCES IN KNOWLEDGE: This largest published systematic analysis on MTT imaging revealed typical but unspecific imaging features that do not allow a reliable, imaging-based differentiation between MTTs and other MPNSTs. Hence, additional histopathological analysis remains essential.

Elexacaftor/tezacaftor/ivacaftor influences body composition in adults with cystic fibrosis: a fully automated CT-based analysis.

A poor nutritional status is associated with worse pulmonary function and survival in people with cystic fibrosis (pwCF). CF transmembrane conductance regulator modulators can improve pulmonary function and body weight, but more data is needed to evaluate its effects on body composition. In this retrospective study, a pre-trained deep-learning network was used to perform a fully automated body composition analysis on chest CTs from 66 adult pwCF before and after receiving elexacaftor/tezacaftor/ivacaftor (ETI) therapy. Muscle and adipose tissues were quantified and divided by bone volume to obtain body size-adjusted ratios. After receiving ETI therapy, marked increases were observed in all adipose tissue ratios among pwCF, including the total adipose tissue ratio (+ 46.21%, p < 0.001). In contrast, only small, but statistically significant increases of the muscle ratio were measured in the overall study population (+ 1.63%, p = 0.008). Study participants who were initially categorized as underweight experienced more pronounced effects on total adipose tissue ratio (p = 0.002), while gains in muscle ratio were equally distributed across BMI categories (p = 0.832). Our findings suggest that ETI therapy primarily affects adipose tissues, not muscle tissue, in adults with CF. These effects are primarily observed among pwCF who were initially underweight. Our findings may have implications for the future nutritional management of pwCF.

Body composition impacts outcome of bronchoscopic lung volume reduction in patients with severe emphysema: a fully automated CT-based analysis.

Chronic Obstructive Pulmonary Disease (COPD) is characterized by progressive and irreversible airflow limitation, with individual body composition influencing disease severity. Severe emphysema worsens symptoms through hyperinflation, which can be relieved by bronchoscopic lung volume reduction (BLVR). To investigate how body composition, assessed through CT scans, impacts outcomes in emphysema patients undergoing BLVR. Fully automated CT-based body composition analysis (BCA) was performed in patients with end-stage emphysema receiving BLVR with valves. Post-interventional muscle and adipose tissues were quantified, body size-adjusted, and compared to baseline parameters. Between January 2015 and December 2022, 300 patients with severe emphysema underwent endobronchial valve treatment. Significant improvements were seen in outcome parameters, which were defined as changes in pulmonary function, physical performance, and quality of life (QoL) post-treatment. Muscle volume remained stable (1.632 vs. 1.635 for muscle bone adjusted ratio (BAR) at baseline and after 6 months respectively), while bone adjusted adipose tissue volumes, especially total and pericardial adipose tissue, showed significant increase (2.86 vs. 3.00 and 0.16 vs. 0.17, respectively). Moderate to strong correlations between bone adjusted muscle volume and weaker correlations between adipose tissue volumes and outcome parameters (pulmonary function, QoL and physical performance) were observed. Particularly after 6-month, bone adjusted muscle volume changes positively corresponded to improved outcomes (ΔForced expiratory volume in 1 s [FEV1], r = 0.440; ΔInspiratory vital capacity [IVC], r = 0.397; Δ6Minute walking distance [6MWD], r = 0.509 and ΔCOPD assessment test [CAT], r = -0.324; all p < 0.001). Group stratification by bone adjusted muscle volume changes revealed that groups with substantial muscle gain experienced a greater clinical benefit in pulmonary function improvements, QoL and physical performance (ΔFEV1%, 5.5 vs. 39.5; ΔIVC%, 4.3 vs. 28.4; Δ6MWDm, 14 vs. 110; ΔCATpts, -2 vs. -3.5 for groups with ΔMuscle, BAR% < -10 vs. > 10, respectively). BCA results among patients divided by the minimal clinically important difference for forced expiratory volume of the first second (FEV1) showed significant differences in bone-adjusted muscle and intramuscular adipose tissue (IMAT) volumes and their respective changes after 6 months (ΔMuscle, BAR% -5 vs. 3.4 and ΔIMAT, BAR% -0.62 vs. 0.60 for groups with ΔFEV1 ≤ 100 mL vs > 100 mL). Altered body composition, especially increased muscle volume, is associated with functional improvements in BLVR-treated patients.

Fibroblast Activation Protein α-Directed Imaging and Therapy of Solitary Fibrous Tumor.

Fibroblast activation protein α (FAPα) is expressed at high levels in several types of tumors. Here, we report the expression pattern of FAPα in solitary fibrous tumor (SFT) and its potential use as a radiotheranostic target. Methods: We analyzed FAPα messenger RNA and protein expression in biopsy samples from SFT patients using immunohistochemistry and multiplexed immunofluorescence. Tracer uptake and detection efficacy were assessed in patients undergoing clinical 68Ga-FAPα inhibitor (FAPI)-46 PET,18F-FDG PET, and contrast-enhanced CT. 90Y-FAPI-46 radioligand therapy was offered to eligible patients with progressive SFT. Results: Among 813 patients and 126 tumor entities analyzed from the prospective observational MASTER program of the German Cancer Consortium, SFT (n = 34) had the highest median FAPα messenger RNA expression. Protein expression was confirmed in tumor biopsies from 29 of 38 SFT patients (76%) in an independent cohort. Most cases showed intermediate to high FAPα expression by immunohistochemistry (24/38 samples, 63%), which was located primarily on the tumor cell surface. Nineteen patients who underwent 68Ga-FAPI-46 PET imaging demonstrated significantly increased tumor uptake, with an SUVmax of 13.2 (interquartile range [IQR], 10.2), and an improved mean detection efficacy of 94.5% (SEM, 4.2%), as compared with 18F-FDG PET (SUVmax, 3.2 [IQR, 3.1]; detection efficacy, 77.3% [SEM, 5.5%]). Eleven patients received a total of 34 cycles (median, 3 cycles [IQR, 2 cycles]) of 90Y-FAPI-46 radioligand therapy, which resulted in disease control in 9 patients (82%). Median progression-free survival was 227 d (IQR, 220 d). Conclusion: FAPα is highly expressed by SFT and may serve as a target for imaging and therapy. Further studies are warranted to define the role of FAPα-directed theranostics in the care of SFT patients.

DOTATOC PET/CT imaging of a typical carcinoid tumor in a human ex-vivo perfused lung lobe.

The use of Isolated lung perfusion (ILP), combined with medical imaging modalities such as positron emission tomography-computed tomography (PET/CT), provides real-time visualization of tumors in ventilated and perfused vital lung tissue. This experiment intends to show the feasibility and benefits of using ILP combined with PET/CT imaging. Following lung surgery on a 49-year-old male, his left lower lobectomy specimen, which held a typical carcinoid tumor, was preserved on normothermic ILP. Gallium-68-Edotreotide ([68Ga]-DOTATOC) was administered into the ILP circuit, and dynamic emission data from PET/CT was acquired. ILP was carried out for 120 minutes. Near physiologic gas exchange and glucose metabolism were preserved throughout the experiment. The time activity curves (TAC) of 5 different volumes of interest (VOI) showed notable differences in tracer uptake over time. The peripheral area of the carcinoid exhibited delayed but high somatostatin receptor agonist uptake compared to the surrounding parenchyma and the intrapulmonary artery. However, the central area of the carcinoid showed very low [68Ga]-DOTATOC uptake. This experiment demonstrates the potential of ILP combined with PET/CT for kinetic modeling in experimental nuclear medicine imaging. By providing visualization of tracer uptake in perfused lung tissue, this model could potentially improve our understanding of tumor physiology and molecular imaging.

Novel 68Ga-FAPI PET/CT Offers Oncologic Staging Without COVID-19 Vaccine-Related Pitfalls.

In the setting of ongoing coronavirus disease 2019 vaccination, vaccine-related tracer uptake in locoregional lymph nodes has become a well-known issue in tumor staging by 18F-FDG PET/CT. 68Ga-fibroblast-activation protein inhibitor (FAPI) PET/CT is a new oncologic imaging tool that may overcome this limitation. Methods: We assessed postvaccine head-to-head and same-day 18F-FDG and 68Ga-FAPI-46 PET/CT findings in a series of 11 patients from a large, prospective imaging registry. All patients with documented tracer uptake in locoregional lymph nodes on PET/CT or PET/MRI, after vaccination within 6 wk, were eligible for investigation. Result: Significant visual lymph node uptake adjacent to the injection site was noted in 11 of 11 (100%) patients with 18F-FDG PET/CT, versus 0 of 11 (0%) with 68Ga-FAPI PET/CT. 18F-FDG detected 73% and 68Ga-FAPI PET/CT 94% of all tumor lesions. Conclusion: In this case-series study, 68Ga-FAPI showed its potential to avoid 18F-FDG PET/CT postvaccination pitfalls and presented superior tumor localization.

Efficacy and Safety of 124I-MIBG Dosimetry-Guided High-Activity 131I-MIBG Therapy of Advanced Pheochromocytoma or Neuroblastoma.

We aim to evaluate the efficacy and safety of 124I-metaiodobenzylguanidine (MIBG) dosimetry-guided high-activity 131I-MIBG therapy of advanced pheochromocytoma or neuroblastoma. Methods: Fourteen patients with advanced pheochromocytoma or neuroblastoma, age 9-69 y, underwent 124I-MIBG PET scans and whole-body retention measurements to assess the whole-body dose as a surrogate of bone marrow toxicity and tumor (absorbed) dose per unit of administered activity. Dosimetry results together with individual patient characteristics were combined to guide a single therapeutic activity to achieve a high tumor dose without exceeding toxicity threshold. Toxicity was assessed for hematologic, hepatic, and renal function. Response was evaluated by RECIST, International Society of Pediatric Oncology Europe Neuroblastoma-like score, change in PET uptake, and quantitative PET parameters (SUVmax, SUVpeak, metabolic tumor volume, total lesion glycolysis), as well as visual decrease in number or in visual intensity of lesions on baseline to follow-up 124I-MIBG PET/CT. Results: The average therapeutic activity was 14 GBq. Eleven of 14 patients (79%) received each more than 10 GBq. One male patient was treated with a single activity of 50 GBq. Three patients were treated with lower activities between 3.5 and 7.0 GBq. Median overall survival was 85 mo (95% CI), and median progression-free survival was 25 mo (95% CI). Four (29%) and 5 (36%) patients demonstrated response (complete response or partial response) by RECIST and functional imaging, respectively. One patient exceeded whole-body dose of 2 Gy and demonstrated grade 3 hematologic toxicity, which resolved spontaneously within 12 mo after the therapy without the need for further treatment. Three patients (21%) demonstrated transient grade 1 renal toxicity. Conclusion: 124I-MIBG dosimetry-guided high-activity 131I-MIBG therapy in patients with advanced pheochromocytoma or neuroblastoma resulted in durable responses with a low rate of manageable adverse events. Efficacy of 124I-MIBG-guided activity escalation should further be assessed in a prospective setting.

Real-Life Experience in the Treatment of Intrahepatic Cholangiocarcinoma by 90Y Radioembolization: A Multicenter Retrospective Study.

Limited treatment options in patients with intrahepatic cholangiocarcinoma (iCCA) demand the introduction of new, catheter-based treatment options. Especially, 90Y radioembolization may expand therapeutic abilities beyond surgery or chemotherapy. Therefore, the purpose of this study was to identify factors associated with an improved median overall survival (mOS) in iCCA patients receiving radioembolization in a retrospective study at 5 major tertiary-care centers. Methods: In total, 138 radioembolizations in 128 patients with iCCA (female, 47.7%; male, 52.3%; mean age ± SD, 61.1 ± 13.4 y) were analyzed. Clinical data, imaging characteristics, and radioembolization reports, as well as data from RECIST, version 1.1, analysis performed 3, 6, and 12 mo after radioembolization, were collected. mOS was compared among different subgroups using Kaplan-Meier curves and the log-rank test. Results: Radioembolization was performed as first-line treatment in 25.4%, as second-line treatment in 38.4%, and as salvage treatment in 36.2%. In patients receiving first-line, second-line, and salvage radioembolization, the disease control rate was 68.6%, 52.8%, and 54.0% after 3 mo; 31.4%, 15.1%, and 12.0% after 6 mo; and 17.1%, 5.7%, and 6.0% after 1 y, respectively. In patients receiving radioembolization as first-line, second-line, and salvage treatment, mOS was 12.0 mo (95% CI, 7.6-23.4 mo), 11.8 mo (95% CI, 9.1-16.6 mo), and 8.4 mo (95% CI, 6.3-12.7 mo), respectively. No significant differences among the 3 groups were observed (P = 0.15). Hepatic tumor burden did not significantly influence mOS (P = 0.12). Conclusion: Especially in advanced iCCA, second-line and salvage radioembolization may be important treatment options. In addition to ongoing studies investigating the role of radioembolization as first-line treatment, the role of radioembolization in the later treatment stages of the disease demands further attention.

Correlation of the apparent diffusion coefficient with the standardized uptake value in meningioma of the skull plane using [68]Ga-DOTATOC PET/MRI.

PURPOSE: To evaluate a correlation between an MRI-specific marker for cellular density [apparent diffusion coefficient (ADC)] and the expression of Somatostatin Receptors (SSTR) in patients with meningioma of the skull plane and orbital space. METHODS: 68 Ga-DOTATOC PET/MR imaging was performed in 60 Patients with suspected or diagnosed meningiomas of the skull base and eye socket. Analysis of ADC values succeeded in 32 patients. ADC values (ADC mean and ADC min ) were analyzed using a polygonal region of interest. Tracer-uptake of target lesions was assessed according to corresponding maximal (SUV max ) and mean (SUV mean ) values. Correlations between assessed parameters were evaluated using the Pearson correlation coefficient. RESULTS: One out of 32 patients (3%) was diagnosed with lymphoma by histopathological examination and therefore excluded from further analysis. Median ADC mean amounted to 822 × 10 -5  mm²/s -1 (95% CI: 570-1497) and median ADC min was 493 × 10 -5 mm 2 /s -1 (95% CI: 162-783). There were no significant correlations between SUV max and ADC min (r = 0.60; P  = 0.76) or ADC mean (r = -0.52; P  = 0.79), respectively. However, Pearson's test showed a weak, inverse but insignificant correlation between ADC mean and SUV mean (r = -0.33; P  = 0.07). CONCLUSION: The presented data displays no relevant correlations between increased SSTR expression and cellularity in patients with meningioma of the skull base. SSTR-PET and DWI thus may offer complementary information on tumor characteristics of meningioma.

Superior Tumor Detection for 68Ga-FAPI-46 Versus 18F-FDG PET/CT and Conventional CT in Patients with Cholangiocarcinoma.

Management of cholangiocarcinoma is among other factors critically determined by accurate staging. Here, we aimed to assess the accuracy of PET/CT with the novel cancer fibroblast-directed 68Ga-fibroblast activation protein (FAP) inhibitor (FAPI)-46 tracer for cholangiocarcinoma staging and management guidance. Methods: Patients with cholangiocarcinoma from a prospective observational trial were analyzed. 68Ga-FAPI-46 PET/CT detection efficacy was compared with 18F-FDG PET/CT and conventional CT. SUVmax/tumor-to-background ratio (Wilcoxon test) and separately uptake for tumor grade and location (Mann-Whitney U test) were compared. Immunohistochemical FAP and glucose transporter 1 (GLUT1) expression of stromal and cancer cells was analyzed. The impact on therapy management was investigated by pre- and post-PET/CT questionnaires sent to the treating physicians. Results: In total, 10 patients (6 with intrahepatic cholangiocarcinoma and 4 with extrahepatic cholangiocarcinoma; 6 with grade 2 tumor and 4 with grade 3 tumor) underwent 68Ga-FAPI-46 PET/CT and conventional CT; 9 patients underwent additional 18F-FDG PET/CT. Immunohistochemical analysis was performed on the entire central tumor plain in 6 patients. Completed questionnaires were returned in 8 cases. Detection rates for 68Ga-FAPI-46 PET/CT, 18F-FDG PET/CT, and CT were 5, 5, and 5, respectively, for primary tumor; 11, 10, and 3, respectively, for lymph nodes; and 6, 4, and 2, respectively, for distant metastases. 68Ga-FAPI-46 versus 18F-FDG PET/CT SUVmax for primary tumor, lymph nodes, and distant metastases was 14.5 versus 5.2 (P = 0.043), 4.7 versus 6.7 (P = 0.05), and 9.5 versus 5.3 (P = 0.046), respectively, and tumor-to-background ratio (liver) was 12.1 versus 1.9 (P = 0.043) for primary tumor. Grade 3 tumors demonstrated a significantly higher 68Ga-FAPI-46 uptake than grade 2 tumors (SUVmax, 12.6 vs. 6.4; P = 0.009). Immunohistochemical FAP expression was high on tumor stroma (∼90% of cells positive), whereas GLUT1 expression was high on tumor cells (∼80% of cells positive). Overall, average expression intensity was estimated as grade 3 for FAP and grade 2 for GLUT1. Positive 68Ga-FAPI-46 PET findings led to a consequent biopsy workup and diagnosis of cholangiocarcinoma in 1 patient. However, patient treatment was not adjusted on the basis of 68Ga-FAPI-46 PET. Conclusion: 68Ga-FAPI-46 demonstrated superior radiotracer uptake, especially in grade 3 tumors, and lesion detection in patients with cholangiocarcinoma. In line with this result, immunohistochemistry demonstrated high FAP expression on tumor stroma. Accuracy is under investigation in an ongoing investigator-initiated trial.