Fibroblast activation protein inhibitor (FAPI) PET for diagnostics and advanced targeted radiotherapy in head and neck cancers.

PURPOSE: Cancer-associated fibroblasts (CAFs) expressing fibroblast activation protein (FAP) have been associated with the aggressive nature of head and neck cancers (HNCs). These tumours grow diffusely, leading to extremely challenging differentiation between tumour and healthy tissue. This analysis aims to introduce a novel approach of tumour detection, contouring and targeted radiotherapy of HNCs using visualisation of CAFs: PET-CT with 68Ga-radiolabeled inhibitors of FAP (FAPI). METHODS: FAPI PET-CT was performed without complications prior to radiotherapy in addition to contrast enhanced CT (CE-CT) and MRI on 14 patients with HNC. First, for tissue biodistribution analysis, volumes of interest were defined to quantify SUVmean and SUVmax in tumour and healthy parenchyma. Secondly, using four thresholds of three-, five-, seven- and tenfold increase of FAPI enhancement in the tumour as compared with normal tissue, four different gross tumour volumes (FAPI-GTV) were created automatically. These were compared with GTVs created conventionally with CE-CT and MRI (CT-GTV). RESULTS: The biodistribution analysis revealed high FAPI avidity within tumorous lesions (e.g. primary tumours, SUVmax 14.62 ± 4.44; SUVmean 7.41 ± 2.39). In contrast, low background uptake was measured in healthy tissues of the head and neck region (e.g. salivary glands: SUVmax 1.76 ± 0.31; SUVmean 1.23 ± 0.28). Considering radiation planning, CT-GTV was of 27.3 ml, whereas contouring with FAPI resulted in significantly different GTVs of 67.7 ml (FAPI × 3, p = 0.0134), 22.1 ml (FAPI × 5, p = 0.0419), 7.6 ml (FAPI × 7, p = 0.0001) and 2.3 ml (FAPI × 10, p = 0.0001). Taking these significant disparities between the GTVs into consideration, we merged FAPI-GTVs with CT-GTVs. This resulted in median volumes, that were, as compared to CT-GTVs, significantly larger with FAPI × 3 (54.7 ml, + 200.5% relative increase, p = 0.0005) and FAPI × 5 (15.0 ml, + 54.9%, p = 0.0122). Furthermore, FAPI-GTVs were not covered by CE-CT-based planning target volumes (CT-PTVs) in several cases. CONCLUSION: We present first evidence of diagnostic and therapeutic potential of FAPI ligands in head and neck cancer. Larger studies with histopathological correlation are required to validate our findings.

Impact of Primary Staging with Fibroblast Activation Protein Specific Enzyme Inhibitor (FAPI)-PET/CT on Radio-Oncologic Treatment Planning of Patients with Esophageal Cancer.

PURPOSE: Quinoline-based ligands targeting cancer-associated fibroblasts have emerged as promising radiopharmaceuticals in different tumor entities. The aim of this retrospective study was to explore the potential of FAPI-PET/CT in the initial staging of esophageal cancer patients and its usefulness in radiotherapy planning as a first clinical analysis. METHODS: Seven patients with treatment-naive esophageal cancer underwent FAPI-PET/CT. Tracer uptake was quantified by standardized uptake values (SUV)max and (SUV)mean. Six patients received definitive and one neoadjuvant (chemo)radiation therapy. Endo-esophageal clipping, the gold standard to define tumor margins not delineable per CT, was performed in three patients. RESULTS: Primary tumors demonstrated high FAPI uptake with a median SUVmax of 17.2. Excellent tumor-to-background ratios resulted in accurate target volume delineation and were found in perfect match with clipping. Detection of regional lymph node metastases facilitated the use of simultaneous integrated boost radiotherapy plans for these patients. CONCLUSION: FAPI-PET/CT may be beneficial for the management of esophageal cancer particularly in planning radiotherapy, but further research is necessary to increase patient number and statistical reliability.

Evaluation of a noninvasive technique for measuring fat-free mass in poultry.

Total body electrical conductivity (TOBEC) has been successfully used to predict fat-free mass and lipid content in various species of mammals and birds. In the current trial, TOBEC was used to predict fat-free mass in broiler chicks through 14d posthatch. To accomplish this, a calibration equation was developed and then tested for accuracy of prediction. It was determined that two calibration equations (hatch to 4 d and 6 to 14 d) were necessary to predict growth. Equations including only the TOBEC reading had R2 values of .92 (6 to 14 d) and .96 (hatch to 4 d). Equations including additional measures of length or weight had slightly improved R2 values. Through the verification of the calibration equations it was found that when the equations were used in the appropriate range, 95% of the variation in fat-free mass was explained. It was determined that TOBEC measures can be used to predict fat-free mass in live broiler chicks to 2 wk posthatch.

Effect of a urease inhibitor and ceiling fans on ascites in broilers. 1. Environmental variability and incidence of ascites.

A low ventilation model to induce ascites was introduced and characterized. In addition, the effect of supplemental air mixing via ceiling fans (CF) and the feeding of a urease inhibitor (0, 125, and 250 ppm) on incidence of ascites were investigated. Twelve environmental chambers were utilized in the trial; six were fitted with CF. Each dietary treatment was replicated twice per CF treatment. One hundred and twenty day-old male commercial broilers were reared per chamber. Atmospheric O2, CO2, and NH3, temperature, and humidity, as well as weekly litter moisture and pH, were monitored. Chamber CO2 levels increased immediately then stabilized. Chamber NH3 levels increased between 2 to 4 wk of age and rapidly declined when ventilation rates were increased to 1 cfm per bird. The CF and dietary treatments had little effect on air or litter variables except for NH3. Supplementing the diet with urease inhibitor resulted in a greater than 50% reduction in cumulative mortality due to ascites and a slight reduction in weekly BW gains. The CF treatment had no effect on production variables such as weekly feed intake, gain, and feed to gain ratio, or survivability due to ascites.