**1. Introduction**

Lung cancer continues to be the tumor disease with the leading number of cancer deaths worldwide [1]. Precise staging is essential for the initiation of adequate therapy [2]. PET/CT with the glucose analog [18F]Fluorodeoxyglucose ([18F]FDG) assumes a central function for staging lung cancer, according to international guidelines [3,4]. [18F]FDG-PET is generally performed as a static scan, at a defined uptake time of 60 to 90 min after intravenous (i.v.) tracer application. However, due to increased [18F]FDG affinity in inflammatory tissue, [18F]FDG-PET is known to have limited specificity for an accurate evaluation of thoracic lymph nodes, especially in the presence of frequently associated tumor inflammatory pulmonary disease. Thus, [18F]FDG-avid lymph nodes must be biopsied before

Atmanspacher, M.; Spengler, W.; Seith, F.; Von Beschwitz, S.; Dittmann, H.; Zender, L.; Smith, A.M.; Casey, M.E.; Nikolaou, K.; et al. Diagnostic Performance of Dynamic Whole-Body Patlak [18F]FDG-PET/ CT in Patients with Indeterminate Lung Lesions and Lymph Nodes. *J. Clin. Med.* **2023**, *12*, 3942. https:// doi.org/10.3390/jcm12123942

**Citation:** Weissinger, M.;

Academic Editors: Arutselvan Natarajan and Filippo Lococo

Received: 5 April 2023 Revised: 22 May 2023 Accepted: 30 May 2023 Published: 9 June 2023

**Copyright:** © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).

surgery or radiotherapy to rule out malignancy histologically [3,4]. However, such an intervention is often difficult and risky in clinical practice due to the often-limited cardiopulmonary reserve. Furthermore, the evaluation of indeterminate lung lesions, which cannot be biopsied due to their location or unfavorable risk–benefit to the patient, is also an indication for PET [3,4].

One way to generate complementary PET information is to quantify the tracer distribution over time. Until recently, this was typically feasible using two workflows with significant limitations. The first option is a dynamic acquisition, where the tracer distribution is continuously measured in a defined but limited anatomical region. Using this method, the axial field of view of current well-established PET scanners (generally between 15 and 30 cm) limits the anatomical coverage, which in turn restricts the dynamic acquisition of whole-body data [5,6]. A second option is a dual-/multi-time-point PET: this technique combines two or more static PET examinations and calculates the difference in [18F]FDG uptake [7–9]. Whereas traditional dynamic PET is not suitable for whole-body staging due to the limited FOV of the PET scanner, dual-time-point imaging has already shown significantly increased accuracy for the assessment of mediastinal lymph node metastases (LNM) in a large meta-analysis of 654 patients with non-small cell lung cancer (NSCLC) [7].

Dynamic whole-body PET data can be produced using an innovative combination of dynamic acquisition at the start of the scan followed by multiple subsequent whole-body scans either in the "step-and-shoot" or in the "continuous-bed-motion" technique. This form of dynamic data acquisition can be used for Patlak kinetic modeling, which enables the assessment of [18F]FDG distribution in different compartments separately for each organ and tissue in the body [10–13]. However, the clinical benefit of this technique and of dynamic information on tumor staging has not been completely elucidated.

Therefore, the aim of this prospective study was to assess the feasibility of dynamic whole-body PET acquisition in a clinical setting and to evaluate the diagnostic performance of parametric imaging in the classification of indeterminate lung lesions and lymph nodes.

### **2. Materials and Methods**

#### *2.1. Study Design*

Thirty-three consecutive patients with indeterminate pulmonary lesions and a clinical indication for [18F]FDG-PET/CT were enrolled into this prospective unicentric trial between June 2019 and April 2022, as shown in detail in the Consolidated Standards of Reporting Trials (CONSORT) flow diagram (Figure 1). This prospective trial was approved by the Institutional Review Board (registry No. 333/2019BO2) and is listed in the German Clinical Trial Register (DRKS-ID: DRKS00017717). All patients signed an informed consent.
