Visualization of Cancer Associated Fibroblasts Using the Novel FAPI PET/CT for Diagnosing and Delineating Lung Cancers for Radiotherapy

Abstract

This analysis aims to introduce a novel approach of lung cancer detection and tumor delineation for radiotherapy using specific visualization of cancer associated fibroblasts: PET-CT with 18F-radiolabeled inhibitors of Fibroblast Activation Protein (FAPI). Prior to radiotherapy and in addition to contrast enhanced CT (CE-CT), FAPI-PET/CT using 18F-FAPI-74 was acquired at 10 min, 1h and 3h after tracer administration in 10 patients with lung cancer. First, for tissue biodistribution analysis, volume of interest was used to quantify SUVmean and SUVmax in tumor and healthy parenchyma. Secondly, using four thresholds of 1.5, 2, 2.5 and 3-fold increase of FAPI enhancement in the tumor as compared to normal tissue, four different gross tumor volumes (FAPI-GTV) were created automatically. These were consensually compared to GTVs created with conventional CE-CT (CT-GTV) by two experienced and board-certified radiation oncologists and nuclear medicine physicians. All patients tolerated the examination well. The biodistribution analysis revealed that tumorous lesions showed high FAPI avidity, e.g. in primary lung tumors, SUVmax was 11.8 at 10 min; 12.7 at 1h and 11.3 at 3h; in lymph node metastases it was 9.9, 10.7, and 9.4. In contrast, low background uptake was measured in healthy tissues of the thorax and the rest of the body, e.g. in the myocard, SUVmax was 1.9, 1.2 and 0.9. So, for most lesions the uptake peaked later than 10 min. p.i. but there was already some wash-out between 1h and 3h p.i. Hence 1h p.i. scans were used for planning radiotherapy. Here, CE-CT based GTV was of 67.4ml (range 25.9 - 343,4ml), whereas contouring with FAPI resulted in significantly different GTVs of 114.2ml (FAPI x1.5) and 98.1ml (FAPI x2). In the consensus read, the PET-segmented volumes were considered more likely to reflect true tumor-spread than the corresponding CT-GTVs. We present first evidence of diagnostic and therapeutic potential of FAPI-ligands in lung cancer radiation oncology. This novel imaging modality provides critical information concerning tumor spread and produces high contrast images with outstanding tumor-to-background ratios. Thus, automated, precise and comprehensive target volume delineation for radiotherapy of lung cancers might be improved by adding FAPI PET/CT information. Further and larger studies are warranted, especially in comparison with FDG PET/CT to show non-inferiority or even superiority of FAPI PET/CT.