Delayed 68Ga-FAPI-46 PET/MR imaging confirms ongoing fibroblast activation in patients after acute myocardial infarction.

Purpose of the Report: Combined cardiac 68Ga-Fibroblast-Activation Protein-alpha inhibitor (FAPI) positron-emission tomography (PET) and cardiac magnetic resonance imaging (MRI) constitute a novel diagnostic tool in patients for the assessment of myocardial damage after an acute myocardial infarction (AMI). Purpose of this pilot study was to evaluate simultaneous Ga-68-FAPI-46-PET/MR imaging in the delayed phase after AMI. Material and Methods: Eleven patients underwent hybrid 68Ga-FAPI-46 PET/MRI post AMI. Standardized uptake values and fibroblast activation volume (FAV) were calculated and correlated with serum biomarkers and MRI parameters. Results: Significant 68Ga-FAPI-46 uptake could be demonstrated in 11 (100 %) patients after a mean period of 30.9 ± 22.0 days. FAV significantly exceeded the infarction size in MRI and showed a good correlation to MRI parameters as well as to serum biomarkers of myocardial damage. Conclusions: 68Ga-FAPI-46 PET/MRI offers molecular and morphological imaging of affected myocardium after AMI. This study demonstrates ongoing fibroblast activation in a delayed phase after AMI and generates hypotheses for future studies while aiming for a better understanding of myocardial remodeling following ischemic tissue damage.

Utility of Integrated PET/MRI for the Primary Diagnostic Work-Up of Patients with Ewing Sarcoma: Preliminary Results.

BACKGROUND: This study was conducted to evaluate the clinical applicability of integrated PET/MRI for staging and monitoring the effectiveness of neoadjuvant chemotherapy in Ewing sarcoma patients. METHODS: A total of 11 juvenile patients with confirmed Ewing sarcoma, scheduled for induction polychemotherapy, were prospectively enrolled for a PET/MR examination before, during and after the end of treatment. Two experienced physicians analysed the imaging datasets. They were asked to perform a whole-body staging in all three examinations and to define treatment response according to the RECIST1.1 and PERCIST criteria for each patient. RESULTS: In eight patients lymph node and/or distant metastases were detected at initial diagnosis. According to the reference standard, three patients achieved complete response, six patients partial response, and one patient showed stable disease while another patient showed progressive disease. RECIST1.1 categorized the response to treatment in 5/11 patients correctly and showed a tendency to underestimate the response to treatment in the remaining six patients. PERCIST defined response to treatment in 9/11 patients correctly and misclassified two patients with a PR as CR. CONCLUSION: PET/MRI may serve as a valuable imaging tool for primary staging and response assessment of juvenile patients with Ewing sarcoma to induction chemotherapy, accompanied by a reasonable radiation dose for the patient.

Multiparametric 18F-FDG PET/MRI-Based Radiomics for Prediction of Pathological Complete Response to Neoadjuvant Chemotherapy in Breast Cancer.

BACKGROUND: The aim of this study was to assess whether multiparametric 18F-FDG PET/MRI-based radiomics analysis is able to predict pathological complete response in breast cancer patients and hence potentially enhance pretherapeutic patient stratification. METHODS: A total of 73 female patients (mean age 49 years; range 27-77 years) with newly diagnosed, therapy-naive breast cancer underwent simultaneous 18F-FDG PET/MRI and were included in this retrospective study. All PET/MRI datasets were imported to dedicated software (ITK-SNAP v. 3.6.0) for lesion annotation using a semi-automated method. Pretreatment biopsy specimens were used to determine tumor histology, tumor and nuclear grades, and immunohistochemical status. Histopathological results from surgical tumor specimens were used as the reference standard to distinguish between complete pathological response (pCR) and noncomplete pathological response. An elastic net was employed to select the most important radiomic features prior to model development. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were calculated for each model. RESULTS: The best results in terms of AUCs and NPV for predicting complete pathological response in the entire cohort were obtained by the combination of all MR sequences and PET (0.8 and 79.5%, respectively), and no significant differences from the other models were observed. In further subgroup analyses, combining all MR and PET data, the best AUC (0.94) for predicting complete pathologic response was obtained in the HR+/HER2- group. No difference between results with/without the inclusion of PET characteristics was observed in the TN/HER2+ group, each leading to an AUC of 0.92 for all MR and all MR + PET datasets. CONCLUSION: 18F-FDG PET/MRI enables comprehensive high-quality radiomics analysis for the prediction of pCR in breast cancer patients, especially in those with HR+/HER2- receptor status.

68Ga-FAPI as a Diagnostic Tool in Sarcoma: Data from the 68Ga-FAPI PET Prospective Observational Trial.

Bone and soft-tissue sarcomas express fibroblast activation protein (FAP) on tumor cells and associated fibroblasts. Therefore, FAP is a promising therapeutic and diagnostic target. Novel radiolabeled FAP inhibitors (e.g., 68Ga-FAPI-46) have shown high tumor uptake on PET in sarcoma patients. Here, we report the endpoints of the 68Ga-FAPI PET prospective observational trial. Methods: Forty-seven patients with bone or soft-tissue sarcomas undergoing clinical 68Ga-FAPI PET were eligible for enrollment into the 68Ga-FAPI PET observational trial. Of these patients, 43 also underwent 18F-FDG PET. The primary study endpoint was the association between 68Ga-FAPI PET uptake intensity and histopathologic FAP expression analyzed with Spearman r correlation. Secondary endpoints were detection rate, positive predictive value (PPV), interreader reproducibility, and change in management. Datasets were interpreted by 2 masked readers. Results: The primary endpoint was met, and the association between 68Ga-FAPI PET uptake intensity and histopathologic FAP expression was significant (Spearman r = 0.43; P = 0.03). By histopathologic validation, PPV was 1.00 (95% CI, 0.87-1.00) on a per-patient and 0.97 (95% CI, 0.84-1.00) on a per-region basis. In cases with histopathologic validation, 27 of 28 (96%) confirmed patients and 32 of 34 (94%) confirmed regions were PET-positive, resulting in an SE of 0.96 (95% CI, 0.82-1.00) on a per-patient and 0.94 (95% CI, 0.80-0.99) on a per-region basis. The detection rate on a per-patient basis in 68Ga-FAPI and 18F-FDG PET was 76.6% and 81.4%, respectively. In 8 (18.6%) patients, 68Ga-FAPI PET resulted in an upstaging compared with 18F-FDG PET. 68Ga-FAPI PET readers showed substantial to almost perfect agreement for the defined regions (Fleiss κ: primary κ = 0.78, local nodal κ = 0.54, distant nodal κ = 0.91, lung κ = 0.86, bone κ = 0.69, and other κ = 0.65). Clinical management changed in 13 (30%) patients after 68Ga-FAPI PET. Conclusion: We confirm an association between tumoral 68Ga-FAPI PET uptake intensity and histopathologic FAP expression in sarcoma patients. Further, with masked readings and independent histopathologic validation, 68Ga-FAPI PET had a high PPV and sensitivity for sarcoma staging.

Evaluation of the Predictive Potential of 18F-FDG PET and DWI Data Sets for Relevant Prognostic Parameters of Primary Soft-Tissue Sarcomas.

BACKGROUND: To evaluate the potential of simultaneously acquired 18F-FDG PET- and MR-derived quantitative imaging data sets of primary soft-tissue sarcomas for the prediction of neoadjuvant treatment response, the metastatic status and tumor grade. METHODS: A total of 52 patients with a high-risk soft-tissue sarcoma underwent a 18F-FDG PET/MR examination within one week before the start of neoadjuvant treatment. For each patient, the maximum tumor size, metabolic activity (SUVs), and diffusion-restriction (ADC values) of the tumor manifestations were determined. A Mann-Whitney-U test was used, and ROC analysis was performed to evaluate the potential to predict histopathological treatment response, the metastatic status or tumor grade. The results from the histopathological analysis served as reference standard. RESULTS: Soft-tissue sarcomas with a histopathological treatment response revealed a significantly higher metabolic activity than tumors in the non-responder group. In addition, grade 3 tumors showed a significant higher 18F-FDG uptake than grade 2 tumors. Furthermore, no significant correlation between the different outcome variables and tumor size or calculated ADC-values could be identified. CONCLUSION: Measurements of the metabolic activity of primary and untreated soft-tissue sarcomas could non-invasively deliver relevant information that may be used for treatment planning and risk-stratification of high-risk sarcoma patients in a pretherapeutic setting.

Evaluation of 18F-FDG PET and DWI Datasets for Predicting Therapy Response of Soft-Tissue Sarcomas Under Neoadjuvant Isolated Limb Perfusion.

Our purpose was to evaluate and compare the clinical utility of simultaneously obtained quantitative 18F-FDG PET and diffusion-weighted MRI datasets for predicting the histopathologic response of soft-tissue sarcoma (STS) to neoadjuvant isolated limb perfusion (ILP). Methods: In total, 37 patients with a confirmed STS of the extremities underwent 18F-FDG PET/MRI before and after ILP with melphalan and tumor necrosis factor-α. For each patient, the maximum tumor size, metabolic activity (SUV), and diffusion restriction (apparent diffusion coefficient, ADC) were determined in pre- and posttherapeutic examinations, and percentage changes during treatment were calculated. Mann-Whitney U testing and receiver-operating-characteristic analysis were used to compare the results of the different quantitative parameters to predict the histopathologic response to therapy. Results from histopathologic analysis after tumor resection served as the reference standard, and patients were defined as responders or nonresponders based on the grading scale by Salzer-Kuntschik. Results: Histopathologic analysis categorized 22 (59%) patients as responders (grades I-III) and 15 (41%) as nonresponders (grades IV-VI). Under treatment, tumors in responders showed a mean reduction in size (-9.7%) and metabolic activity (SUVpeak, -51.9%; SUVmean, -43.8%), as well as an increase of the ADC values (ADCmin, +29.4%; ADCmean, +32.8%). The percentage changes in nonresponders were -6.2% in tumor size, -17.3% in SUVpeak, -13.9% in SUVmean, +15.3% in ADCmin, and +14.6% in ADCmean Changes in SUV and ADCmean significantly differed between responders and nonresponders (<0.01), whereas differences in tumor size and ADCmin did not (>0.05). The corresponding AUCs were 0.63 for tumor size, 0.87 for SUVpeak, 0.82 for SUVmean, 0.63 for ADCmin, 0.84 for ADCmean, and 0.89 for ratio of ADCmean to SUVpeakConclusion: PET- and MRI-derived quantitative parameters (SUV and ADCmean) and their combination performed well in predicting the histopathologic therapy response of STS to neoadjuvant ILP. Therefore, integrated PET/MRI could serve as a valuable tool for pretherapeutic assessment as well as monitoring of neoadjuvant treatment strategies of STS.

Volumetric PET Response Assessment Outperforms Conventional Criteria in Patients Receiving High-Dose Pembrolizumab for Malignant Mesothelioma.

Fixed-dose pembrolizumab (200 mg absolute, day 1, every 3 wk) for the treatment of malignant pleural mesothelioma did not result in survival benefit in the phase 3 PROMISE-meso trial compared with second-line chemotherapy. Because of lack of validated imaging response criteria, responder subgroups with potential survival benefit have not yet been identified. Here, we administered high-dose pembrolizumab (10 mg/kg, day 1, every 2 wk) considering the KEYNOTE-028 trial and assessed the prognostic value of PET metabolic response in patients with chemotherapy-resistant malignant mesothelioma of the pleura or peritoneum. Methods: Data from 27 patients with baseline and follow-up 18F-FDG PET/CT imaging were retrospectively analyzed. RECIST, version 1.1; modified RECIST; and PERCIST using both tumor lesion metabolic activity in a 1 cm3 spheric region of interest of up to 5 target lesions (PERCISTSULpeak) and metabolic tumor volume PERCIST (PERCISTMTV) were applied separately to categorize responders in CT and PET imaging studies. Progression-free survival (PFS) and overall survival (OS) were compared between responders and nonresponders using Kaplan-Meier and log-rank analyses. Programmed cell death protein 1 ligand expression status was assessed, and its association with outcome was investigated. Results: Twenty-seven patients had 18F-FDG PET/CT imaging at baseline and after at least 4 cycles pembrolizumab. Median PFS and OS were 3.4 and 15.1 mo, respectively. Response rates were 7%, 7%, 30%, and 30% based on RECIST, modified RECIST, PERCISTSULpeak, and PERCISTMTV response criteria, respectively. Response according to PERCISTMTV predicted prolonged OS or PFS (P < 0.01), whereas all other imaging criteria and programmed cell death protein 1 ligand expression did not. Conclusion:18F-FDG PET metabolic volume response predicts survival in patients with malignant mesothelioma receiving high-dose pembrolizumab. These results should prompt inclusion of PET response assessment in future phase 3 clinical trials.

[Hybrid imaging in prostate cancer : Status quo and future applications]. / Hybridbildgebung beim Prostatakarzinom : Status quo und zukünftige Entwicklungen.

BACKGROUND: Recently, the use of prostate-specific membrane antigen (PSMA) tracers like 68Ga-PSMA-11 in positron emission tomography (PET) have shown promising results and are helping to improve care for patients with prostate cancer (PC). PURPOSE: In the following we review the current literature on PSMA-ligand PET, in particular with regard to the currently increasing replacement of 68Ga-PSMA ligands by 18F-labeled PSMA ligands. RESULTS: PSMA-ligand PET is most frequently used for biochemical recurrence. Here, 68Ga-PSMA-11 PET/CT shows superior detection rates compared to conventional imaging modalities, especially in small, morphologically unsuspicious lesions, even at low PSA values. Furthermore, 68Ga-PSMA PET imaging seems to be an encouraging alternative for staging of high-risk patients, particularly in combination with multiparametric MRI. CONCLUSION: The use of PSMA-ligand PET has revolutionized PC imaging. Thus, PSMA-ligand PET is expected to play an even greater role in PC diagnostics in the future, especially as 18F-labeled PSMA ligands are now increasingly used. However, simultaneous image analysis of PET and CT as well as a differentiated image evaluation (clinical context, knowledge of common pitfalls) is mandatory.

18F-FDG PET/MRI for Therapy Response Assessment of Isolated Limb Perfusion in Patients with Soft-Tissue Sarcomas.

Our purpose was to assess the diagnostic potential of simultaneously acquired 18F-FDG PET and MRI data sets for therapy response assessment of isolated limb perfusion (ILP) in patients with soft-tissue sarcomas (STS). Methods: In total, 45 patients with histopathologically verified STS were prospectively enrolled for an integrated 18F-FDG PET/MRI examination before and after ILP. Therapy response was assessed based on different MRI- and PET-derived morphologic (RECIST and the MR-adapted Choi criteria) and metabolic (PERCIST) criteria. In addition, a regression model was used combining relative changes in quantitative variables to predict treatment response under ILP. Histopathologic results after subsequent tumor resection served as the reference standard, and patients were categorized as responders or nonresponders on the basis of the 6-stage regression scale by Salzer-Kuntschik. Results: Histopathologic analysis categorized 27 patients as responders (grades I-III) and 18 patients as nonresponders (grades IV-VI). Calculated sensitivity, specificity, positive and negative predictive values, and diagnostic accuracy were 22%, 89%, 75%, 43%, and 49% for RECIST; 70%, 44%, 66%, 50%, and 60% for the Choi criteria; and 85%, 78%, 85%, 78%, and 82% for PERCIST. Receiver-operating-characteristic analysis revealed an area under the curve (AUC) of 0.56 for RECIST, 0.57 for the Choi criteria, and 0.82 for PERCIST. The combined regression model revealed higher values (AUC, 0.90) than for the stand-alone analysis, however, differences to metabolic parameters did not reach significance (P value: 0.067). Conclusion: Our study demonstrates the superiority of 18F-FDG PET over MRI data sets for response assessment of STS under neoadjuvant ILP. In a clinical setting, MRI delivers valuable information for presurgical assessment. Therefore, combining 18F-FDG PET and MRI data may enable more reliable treatment planning and therapy monitoring of STS.