Evaluation of Musculoskeletal and Pulmonary Bacterial Infections With [I]FIAU PET/CT

Purpose: Imaging is limited in the evaluation of bacterial infection. Direct imaging of in situ bacteria holds promise for noninvasive diagnosis. We investigated the ability of a bacterial thymidine kinase inhibitor ([ 124 I]FIAU) to image pulmonary and musculoskeletal infections. Methods: Thirty-three patients were prospectively accrued: 16 with suspected musculoskeletal infection, 14 with suspected pulmonary infection, and 3 with known rheumatoid arthritis without infection. Thirty-one patients were imaged with [ 124 I]FIAU PET/CT and 28 with [ 18 F]FDG PET/CT. Patient histories were reviewed by an experienced clinician with subspecialty training in infectious diseases and were determined to be positive, equivocal, or negative for infection. Results: Sensitivity, specificity, positive-predictive value, negative-predictive value, and accuracy of [ 124 I]FIAU PET/CT for diagnosing infection were estimated as 7.7% to 25.0%, 0.0%, 50%, 0.0%, and 20.0% to 71.4% for musculoskeletal infections and incalculable-100.0%, 51.7% to 72.7%, 0.0% to 50.0%, 100.0%, and 57.1% to 78.6% for pulmonary infections, respectively. The parameters for [ 18 F]FDG PET/CT were 75.0% to 92.3%, 0.0%, 23.1% to 92.3%, 0.0%, and 21.4% to 85.7%, respectively, for musculoskeletal infections and incalculable to 100.0%, 0.0%, 0.0% to 18.2%, incalculable, and 0.0% to 18.2% for pulmonary infections, respectively. Conclusions: The high number of patients with equivocal clinical findings prevented definitive conclusions from being made regarding the diagnostic efficacy of [ 124 I]FIAU. Future studies using microbiology to rigorously define infection in patients and PET radiotracers optimized for image quality are needed

Cardiosphere-Derived Cells Demonstrate Metabolic Flexibility That Is Influenced by Adhesion Status

Adult stem cells demonstrate metabolic flexibility that is regulated by cell adhesion status. The authors demonstrate that adherent cells primarily utilize glycolysis, whereas suspended cells rely on oxidative phosphorylation for their ATP needs. Akt phosphorylation transduces adhesion-mediated regulation of energy metabolism, by regulating translocation of glucose transporters (GLUT1) to the cell membrane and thus, cellular glucose uptake and glycolysis. Cell dissociation, a pre-requisite for cell transplantation, leads to energetic stress, which is mediated by Akt dephosphorylation, downregulation of glucose uptake, and glycolysis. They designed hydrogels that promote rapid cell adhesion of encapsulated cells, Akt phosphorylation, restore glycolysis, and cellular ATP levels

Development of [F]FPy-WL12 as a PD-L1 Specific PET Imaging Peptide

Expression of programmed cell death ligand 1 (PD-L1) within tumors is an important biomarker for guiding immune checkpoint therapies; however, immunohistochemistry-based methods of detection fail to provide a comprehensive picture of PD-L1 levels in an entire patient. To facilitate quantification of PD-L1 in the whole body, we developed a peptide-based, high-affinity PD-L1 imaging agent labeled with [ 18 F]fluoride for positron emission tomography (PET) imaging. The parent peptide, WL12, and the nonradioactive analog of the radiotracer, 19 FPy-WL12, inhibit PD-1/PD-L1 interaction at low nanomolar concentrations (half maximal inhibitory concentration [IC 50 ], 26-32 nM). The radiotracer, [ 18 F]FPy-WL12, was prepared by conjugating 2,3,5,6-tetrafluorophenyl 6-[ 18 F]fluoronicotinate ([ 18 F]FPy-TFP) to WL12 and assessed for specificity in vitro in 6 cancer cell lines with varying PD-L1 expression. The uptake of the radiotracer reflected the PD-L1 expression assessed by flow cytometry. Next, we performed the in vivo evaluation of [ 18 F]FPy-WL12 in mice bearing cancer xenografts by PET imaging, ex vivo biodistribution, and blocking studies. In vivo data demonstrated a PD-L1-specific uptake of [ 18 F]FPy-WL12 in tumors that is reduced in mice receiving a blocking dose. The majority of [ 18 F]FPy-WL12 radioactivity was localized in the tumors, liver, and kidneys indicating the need for optimization of the labeling strategy to improve the in vivo pharmacokinetics of the radiotracer