*2.2. PET/CT Examination Protocol*

Patients were asked to fast for at least 6 h prior to examination. Weight, size, and blood sugar level were measured before i.v. tracer administration. Blood glucose level was below 140 mg/dL in all patients without the administration of insulin 8 h prior to tracer application. [18F]FDG dosing was weight-based using 4.0 ± 0.6 MBq/kg. All patients were positioned with arms up on a vacuum mattress on the PET/CT (Biograph mCT, Siemens Healthineers) table to reduce motion artifacts and were asked to breathe as calmly and steadily as possible.

Before PET, a full diagnostic CT with adaptable tube voltage and tube current (CARE KV 120–140 kV, CARE Dose 4D 40–280 mAs) was performed. An iodinated contrast agent (80–100 mL Ultravist® 370, Bayer Vital GmbH, Leverkusen, Germany) was administered to all patients except for contraindications.

The dynamic PET acquisition started simultaneously with the i.v. injection of [18F]FDG and lasted a total of 80 min. The initial table position was centered over the cardiac region (BI ≈ 6 min) to acquire the individual input function followed by whole-body (WB) dynamic PET of skull to mid-thigh (WB ≈ 74 min) using continuous-bed-motion as described in detail by Karakatsanis et al. and Rahmim et al. [10–12].

**Figure 1.** CONSORT flow diagram for patient enrolment. PET = Positron Emission Tomography; CT = Computer Tomography.

Image data were subdivided into 43 time frames (12 × 5 s, 6 × 10 s, 8 × 30 s, 7 × 180 s, and 10 × 300 s.) The time activity curve (TAC) was derived by an automatically generated cylindric volume of interest (VOI: 10 mm diameter and 20 mm long) centered in the descending aorta with acquired CT images using ALPHA (automated learning and parsing of human anatomy) as implemented in the vendor's software (VG70A, Siemens Healthcare GmbH, Erlangen, Germany).

### *2.3. Reconstruction and Postprocessing*

Dynamic PET data (cardiac region and WB) were reconstructed with OSEM 3D reconstruction applying point-spread-function (PSF) and time-of-flight (TOF)—using two iterations, 21 subsets, a 200 × 200 matrix, and a 5 mm Gaussian filter. The reconstructed passes 12–17 of the WB and the resulting TAC were used to perform the Patlak reconstructions with two iterations, 21 subsets, a 200 × 200 matrix, and a Gaussian 5 mm filter as implemented in the vendor's software (VG70A, Siemens Healthcare GmbH).

A standard of care static whole-body image was reconstructed by using passes 15–17 of the WB, with ultraHD-PET (PSF + TOF), two iterations, 21 subsets, and a 400 × 400 matrix with a Gaussian 2 mm filter.

[ 18F]FDG kinetics were modeled using a two-compartment model based on linear Patlak analysis [14,15], as described in detail by A. M. Smith et al. [16], resulting in the generation of whole-body Patlak slope and Patlak intercept parametric images. Patlak slope, which represents the constant influx rate of [18F]FDG (Kimean, given in mL/(min × 100 mL) = 0.01 × min−1), was multiplied by the blood glucose level to calculate the metabolic rate of [18F]FDG (MR-FDGmean) and is expressed as <sup>μ</sup>mol/(min × 100 mL). Patlak intercept is expressed in percent and represents the distribution volume of free [18F]FDG (DV-FDGmean) in the reversible compartments and fractional blood volume [13]. Semiquantitative measurements were performed in static images using SUVmax, SUVmean (50% isocontour), and SUVpeak (1 mL sphere).
