Pandey, Mukesh K.

Abstract A low-cost, easy-to-adopt noninvasive imaging modality for differentiating bacterial infection from inflammation is desirable to accurately diagnose bacterial infections. Herein, a bacteria-specific PET probe, [68Ga]Ga-BP, was developed and evaluated in rat models of foreign body-associated osteomyelitis induced by methicillin-resistant Staphylococcus aureus, Pseudomonas aeruginosa, and Klebsiella pneumoniae and was directly compared with sterile inflammation and uninstrumented uninfected controls. [68Ga]Ga-BP-based imaging of MRSA-infected tibiae was also compared to [68Ga]Ga-citrate and [18F]FDG. After iron depletion, dynamic PET/CT imaging was performed at 15–120 min postinjection of radiotracers, followed by assessment of ex vivo biodistribution. [68Ga]Ga-BP successfully detected tibial infection and demonstrated >6-fold higher uptake in infected tibiae with all three bacterial species versus contralateral tibiae via PET imaging. [68Ga]Ga-BP outperformed [68Ga]Ga-citrate and [18F]FDG in identifying MRSA infection. [68Ga]Ga-BP represents a promising, noninvasive PET imaging agent for direct bacterial detection and bacterial infection treatment monitoring.

Introduction There is a growing interest in therapy applications of cell-free extracellular vesicles (EVs) but systemically administered EVs predominantly accumulate in the liver and thereby limit their applications in extrahepatic tissues. One way of diverting EVs to extrahepatic tissues is by tethering or expressing targeting vectors onto the surface of EVs but this requires chemical or genetic modifications with potential drawbacks. There is an unmet need to direct systemically administered EVs to a desired site without genetic or chemical modifications. Methods Herein, we employed positron emission tomography imaging of 89 Zr-labeled EVs to explore the ability of various substances to alter EV trafficking in the body. Results and discussion Subcutaneous injections of phenothiazine and poly(ethylene) glycol into the hind limb of BALB/c mice significantly increased the accumulation of intravenously administered 89 Zr-labeled EVs to the hind limb. Expanding these findings, we investigated EVs isolated from various sources, the influence of timing of the administration of phenothiazine with respect to labeled EV administration, and the relationship of the trafficking of EVs to the site of phenothiazine administration with overall change in biodistribution. The findings support further exploration of phenothiazine analogs for site specific enhancement of EV trafficking in therapeutic applications.