Monitoring the therapeutic effect of long-circulation liposomal glucocorticoids in a murine arthritis model using 18F-FDG PET/CT

Corticosteroids, such as Prednisolon Phosphate (PLP), are widely prescribed to patients with chronic inflammatory disorders. Although the treatment with corticosteroids is highly effective, high and frequent dosages are often required due to poor accumulation at target sites and rapid elimination of the drug. This leads to high incidences of adverse effects. To enhance therapeutic activity and at the same time reduce systemic side effects, current efforts include drug targeting by liposomal encapsulation (Figure 1). Polyethyleneglycol (PEG)-liposomes are long-circulating and accumulate at the site of inflammation due to the enhanced permeability and retention effect in these tissues. It has been shown that plasma concentration of the drug (PLP) and its therapeutic effect increases when encapsulated in liposomes in rate with experimental arthritis (Figure 2).

In this study we aim to monitor the therapeutic effects of this liposomal PLP formulation in mice with antigen induced arthritis (AIA) using 2-Deoxy-2-[ 18F] fluoroglucose (FDG) positron emission tomography/computed tomography (PET/CT). 18F-FDG accumulation increases with the progression of joint swelling and reflects the characteristics changes in pathological progression, which makes 18F-FDG PET/CT a valuable method to assess disease activity and therefore early therapeutic effects. This non-invasive imaging modality is used to visualize the inflammation and the therapeutic effects (Figure 3).

Therapeutic principle.png

Figure 1. Therapeutic principle of liposomal treatment with corticosteroids. Liposomal encapsulation of the drug leads to direct and specific liberation of active drug at inflamed target tissue, higher local concentration of drug and reduction of unwanted side effects.

Plasma concentration.png

Figure 2. Plasma concentration and therapeutic effect of PLP in antigen induced arthritis in rats.

Plasma concentration
● PLP after i.v. 5 mg/kg liposomal PLP
○ Prednisolon after i.v. 5 mg/kg
■ Liposomal PLP
□ PLP after i.v. 5 mg/kg unencapsulated PLP
Therapeutic effect
□ Saline
○ Empty PEG liposomes
■ 7 daily injections of 10 mg/kg free PLP
□ Single injection of 10 mg/kg PLP-PEG liposomes
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Figure 3. Development antigen induced arthritis in male C57Bl6J mice. 18F-FDG PET/CT images of mouse with AIA. 18F-FDG in PBS (10 MBq) was injected i.v. under anesthesia, images were acquired 45 minutes p.i.