Anti-FAP monoclonal antibody, clone NN1728-27G61

Objectives: Targeting Fibroblast Activation Protein (FAP) is a new approach for glioblastoma imaging. In a recent pilot study glioblastomas showed elevated tracer uptake with high intratumoral heterogeneity in projection on the corresponding T2w/FLAIR and contrast enhanced MRI lesions. In this study, we correlated FAP-specific signaling with apparent diffusion coefficient (ADC) and relative cerebral blood volume (rCBV) signals in MRI to further characterize the significance of FAP uptake. Methods: Clinical PET/CT scans of 13 glioblastoma patients were performed post i. v. administration of Ga-68-labelled-FAP-specific tracer molecules. PET- and corresponding MRI-scans were co-registrated. 3d volumetric segmentations were performed of T2w/FLAIR lesions and contrast enhancing lesions within co-registrated MRI slides. Signal intensity values of FAP-specific PET signaling, ADC and rCBV were analyzed for their pixel wise correlation in each patient. Pooled estimates of the correlation coefficients were calculated by using the Fisher z-transformation. Results: FAP-specific PET signals showed a moderately positive correlation with rCBV values which is more pronounced within the T2w/FLAIR lesion (pooled correlation 0,229) than in the contrast enhancing tumor region (pooled correlation 0.09). FAP-specific PET signals showed no correlation with ADC values. Conclusions: The moderately positive correlation of FAP-specific signals with rCBV values in MRI indicates that FAP-signaling is not independent from perfusion, but also does not only reflect intratumoral perfusion differences. The missing correlation of FAP-specific signals with ADC indicates that FAP-specific imaging does not reflect cell density, but the spot-like expression of FAP in glioblastomas. The clinical value of FAP-specific imaging needs further investigation.

Simple Summary Pain scales are tools developed to improve pain assessment in horses. They are based on behaviors and/or facial expressions, and the observer allocates a score based on the character of the behavior or facial expression. Little is known about behaviors and facial expressions at rest in horses with orthopedic pain since pain is mainly assessed by lameness evaluation during movement. The aim of this study was to describe how closely equine behaviors and facial expressions are associated with movement asymmetry and to identify combinations of behavior and expressions present in horses with induced orthopedic pain. Orthopedic pain was induced in eight horses and assessed in two ways; using four existing equine pain scales at rest, and by measuring movement asymmetry during movement. The association of behavior and facial expression items in the pain scales with actual lameness was analyzed. Posture-related behavior showed the strongest association, while facial expressions varied between horses. These results show that pain scales for orthopedic pain assessment would benefit from including posture, head position, location in the box stall, focus, interactive behavior, and facial expressions. This could improve orthopedic pain detection in horses during rest with mild lameness. Equine orthopedic pain scales are targeted towards horses with moderate to severe orthopedic pain. Improved assessment of pain behavior and pain-related facial expressions at rest may refine orthopedic pain detection for mild lameness grades. Therefore, this study explored pain-related behaviors and facial expressions and sought to identify frequently occurring combinations. Orthopedic pain was induced by intra-articular LPS in eight horses, and objective movement asymmetry analyses were performed before and after induction together with pain assessments at rest. Three observers independently assessed horses in their box stalls, using four equine pain scales simultaneously. Increase in movement asymmetry after induction was used as a proxy for pain. Behaviors and facial expressions commonly co-occurred and were strongly associated with movement asymmetry. Posture-related scale items were the strongest predictors of movement asymmetry. Display of facial expressions at rest varied between horses but, when present, were strongly associated with movement asymmetry. Reliability of facial expression items was lower than reliability of behavioral items. These findings suggest that five body behaviors (posture, head position, location in the box stall, focus, and interactive behavior) should be included in a scale for live assessment of mild orthopedic pain. We also recommend inclusion of facial expressions in pain assessment.