Static and dynamic 68Ga-FAPI PET/CT for the detection of malignant transformation of intraductal papillary mucinous neoplasia of the pancreas.

Purpose: Pancreatic ductal adenocarcinoma (PDAC) may arise from intraductal papillary-mucinous neoplasms (IPMN) with malignant transformation, but a significant portion of IPMN remains to show benign behavior. Therefore, it is important to differentiate between benign IPMN and IPMN lesions undergoing malignant transformation. However, non-operative differentiation by ultrasound, CT, MRI and carbohydrate antigen 19-9 (CA19-9) is still unsatisfactory. Here, we assessed the clinical feasibility of additional assessment of malignancy by positron emission tomography using 68Gallium-labeled Fibroblast Activation Protein Inhibitors (68Ga-FAPI-PET) in 25 patients with magnetic resonance imaging (MRI) - or computed tomography (CT) - proven cystic pancreatic lesions. Methods: 25 patients with cystic pancreatic lesions who were followed up in the European Pancreas Center of Heidelberg University hospital and who were led to surgical resection or fine needle aspiration (FNA) due to suspicious clinical, laboratory chemistry or radiological findings were examined by static (all patients) and dynamic (20 patients) 68Ga-FAPI-PET. Cystic pancreatic lesions were delineated and maximum and mean standardized uptake values (SUVmax / SUVmean) were determined. Time activity curves and dynamic parameters (time to peak, K1, k2, K3, k4) were extracted from dynamic PET data. Receiver operating curves (ROC) of static and dynamic PET parameters were calculated. Results: 11 of the patients suffered from menacing IPMN (high grade IPMN with (6 cases) or without (5 cases) progression into PDAC) and 11 from low grade IPMN, 3 patients from other benign entities. Menacing IMPN showed significantly elevated 68Ga-FAPI uptake compared to low grade IPMN and other benign cystic lesions. In dynamic imaging, menacing IPMN showed increasing time activity curves (TAC) followed by slow decrease afterwards, TAC of low grade IPMN showed an immediate peak followed by rapid decrease for about 10 minutes and slower decrease for the rest of the time. ROC curves showed high sensitivity and specificity (area under the curve (AUC) greater than 80%) of static and dynamic PET parameters for the differentiation of IPMN subtypes. Conclusion: 68Ga-FAPI-PET is a helpful new tool for the differentiation of menacing and low grade IPMN and shows the potential to avoid unnecessary surgery for non-malignant pancreatic IPMN

A global Staphylococcus aureus proteome resource applied to the in vivo characterization of host-pathogen interactions.

Data-independent acquisition mass spectrometry promises higher performance in terms of quantification and reproducibility compared to data-dependent acquisition mass spectrometry methods. To enable high-accuracy quantification of Staphylococcus aureus proteins, we have developed a global ion library for data-independent acquisition approaches employing high-resolution time of flight or Orbitrap instruments for this human pathogen. We applied this ion library resource to investigate the time-resolved adaptation of S. aureus to the intracellular niche in human bronchial epithelial cells and in a murine pneumonia model. In epithelial cells, abundance changes for more than 400 S. aureus proteins were quantified, revealing, e.g., the precise temporal regulation of the SigB-dependent stress response and differential regulation of translation, fermentation, and amino acid biosynthesis. Using an in vivo murine pneumonia model, our data-independent acquisition quantification analysis revealed for the first time the in vivo proteome adaptation of S. aureus. From approximately 2.15 × 1

Comparison of early and late 68Ga-FAPI-46-PET in 33 patients with possible recurrence of pancreatic ductal adenocarcinomas

Abstract Positron emission tomography with 68Gallium (68Ga) labeled inhibitors of fibroblast activation protein (68Ga-FAPI-PET) is a promising imaging technique for patients with recurrent pancreatic ductal adenocarcinomas (PDAC). To date, it is not clear if different acquisition timepoints for 68Ga-FAPI-PET may result in comparable imaging information and if repetitive 68Ga-FAPI-PET imaging may add diagnostic value to single timepoint acquisition for recurrent PDAC. Here we analyzed retrospectively early (20 min p.i.) and late (60 min p.i.) 68Ga-FAPI-PET imaging using FAPI-46 of 33 patients with possible recurrence of PDAC concerning detection rates and uptake over time of local recurrences, metastases, inflammatory lesions of the pancreas, cholestatic lesions of the liver and reactive tissue. 33 patients with histologically confirmed PDAC after complete or partial resection of the pancreas and possible recurrence were examined by 68Ga-FAPI-46-PET acquired 20- and 60-min post injection (p.i.) of the radiotracer. FAPI-positive lesions were classified as local recurrences, metastases, inflammatory lesions of the pancreas (ILP), cholestatic lesions of the liver and reactive tissue based on histology, PET- and CT-morphology and clinical information. Lesions were contoured, and standardized uptake values (SUVmax and SUVmean) and target-to-background ratios (TBR) were analyzed for both acquisition timepoints. In total, 152 FAPI-positive lesions (22 local relapses, 47 metastases, 26 inflammatory lesions of the pancreas, 28 reactive tissues, and 29 cholestatic lesions) were detected. Detection rates for the early and late acquisition of 68Ga-FAPI-46-PET were almost identical except cholestatic lesions, which showed a higher detection rate at early imaging. SUV parameters and TBRs of ILP significantly decreased over time. Cholestatic lesions showed a tendency towards decreasing uptake. All other types of lesions showed relatively stable uptake over time. Early and late acquisition of 68Ga-FAPI-PET results in comparable imaging information in patients with possible recurrence of PDAC. Two timepoint imaging offers additional diagnostic potential concerning differential diagnoses