E soft software

The ⁶⁸Ga-PSMA-617 PET/CT images were reviewed by consensus between three experienced nuclear medicine physicians by using Siemens MMWP workstation. PCa lesions were distinguished from the surrounding normal prostate tissues by visual analysis. To calculate the ⁶⁸Ga-PSMA-617 uptake of the primary PCa lesion, circular regions of interest (ROIs) were drawn around areas with focally increased uptake in transaxial slices by using e.soft software (Siemens) at a 30% threshold, and SUVmax was calculated automatically. Scans were considered positive when the focal uptake of ⁶⁸Ga-PSMA-617 was superior to the background activity. Semiquantitative measures comprised SUVmax and SUVratio (explained below under “Statistical analysis”).
The positive criterion for mpMRI is an abnormal focal signal increase or decrease. The readers were instructed to decide on the basis of their overall impression by using the 5-point Prostate Imaging Reporting and Data System (PI-RADS) score^{19 (link)}: 1, PCa highly unlikely; 2, PCa unlikely; 3, equivocal PCa; 4, PCa likely; and 5, PCa highly likely. At the patient level, data were dichotomized (score of 1–2, PCa negative; score of 3–5, PCa positive) using the highest score per patient.

Tracer uptake in all patients was determined by quantification of mean and maximum standardized uptake values (SUVmean and SUVmax). Regarding SUV calculation, circular volumes of interest were drawn around tumor lesions on transaxial slices and automatically adapted to a 3-dimensional VOI with e.soft software (Siemens) at a 60% isocontour. Evaluation of normal organs was conducted with a 1 cm diameter (for the small organs thyroid, parotid gland, myocardium, oral mucosa, spinal cord, ovaries) or 2 cm diameter (brain, muscle, liver, pancreas, spleen, kidney, fat, aortic lumen content, lung, mamma, endometrium) sphere placed inside the organ parenchyma. Tumor-to-background ratios (TBRs) were determined for quantification of image contrast. The geometric mean of the quotients of lesion (SUVmax) to background tissue (SUVmean) formed the TBR, measured for metastases in lymph nodes (relative to fat tissue), bone (relative to bone spongiosa), liver (relative to liver parenchyma), peritoneal carcinomatosis (relative to fat), and lung (relative to lung parenchyma). Additionally, the TBRs of all identified tumors were formed in relation to blood pool, muscle, and fat tissue. The ⁶⁸ Ga-FAPI-PET/CT scans were analyzed by one board-certified radiologist, one board-certified radiation oncologist, and two board-certified nuclear medicine physicians in consensus.

The tracer biodistribution in patients was quantified by SUV_mean and SUV_max at 1 h after injection for ⁶⁸Ga-FAPI-2, ⁶⁸Ga-FAPI-4, and ¹⁸F-FDG. The interval between ¹⁸F-FDG and ⁶⁸Ga-FAPI examinations was 9 d maximum, and no treatment change took place in between. For calculation of the SUV, circular regions of interest were drawn around the tumor lesions with focally increased uptake in transaxial slices and automatically adapted to a 3-dimensional volume of interest with e.soft software (Siemens) at a 40% isocontour. The normal organs were evaluated with a 1-cm-diameter (for the small organs [thyroid, parotid gland, myocardium, oral mucosa, and spinal cord]) to 2-cm-diameter (brain, muscle, liver, spleen, kidney, fat, aortic lumen content, and lung) sphere placed inside the organ parenchyma.