Synovial ablation in a rabbit rheumatoid arthritis model using photodynamic therapy
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Published on: April 3, 2016
Andrew D Beischer1, Prithi Bhathal, Richard de Steiger
1University of Melbourne Department of Surgery, Royal Melbourne Hospital, Melbourne, Victoria, Australia. adbeisch@netspace.net.au
Background:
At present there is no ideal minimally invasive method for ablating inflamed synovium in joints that has been unresponsive to optimal medical management in patients with rheumatoid arthritis. The aim of this study was to determine whether photo-dynamic therapy could be used for this purpose.
Methods:
In a rabbit knee model of rheumatoid arthritis the pharmacokinetics of the photosensitizer Haematoporphyrin Derivative (HpD) into periarticular tissues and blood was measured following intravenous injection of HpD. The second phase of the study was to determine the histological effect of HpD activation by 63 nm light delivered via an intra-articular optic fibre using a dye pumped KTP-YAG laser. The light dose was varied from 0-200 joule/cm2.
Results:
Pharmacokinetic studies determined that inflamed synovium rapidly accumulated HpD, with peak levels being reached 12 h following intravenous injection. The ratio of HpD uptake into inflamed synovium versus peri-articular quadriceps muscle was found to be 22.8. Histological examination of the treated knees indicated that selective destruction of inflamed synovium was achieved at light doses 100 joules/cm2 and above. No significant effect was observed on normal intra-articular tissues.
Conclusion:
We have demonstrated that the first generation photosensitizer HpD selectively accumulates within inflamed -synovium. Activation of HpD by intra-articular light administration resulted in selective ablation of the inflamed synovium. These findings indicate that PDT offers potential as a new selective, minimally invasive synovectomy technique.
Insights
Photo-dynamic therapy (PDT) selectively targets inflamed synovium in rheumatoid arthritis. This minimally invasive technique uses a photosensitizer and laser light to ablate diseased tissue, offering a new treatment option.
Area of Science:
- Biomedical Engineering
- Photochemistry
- Rheumatology
Background:
- Current minimally invasive methods for rheumatoid arthritis synovium ablation are insufficient.
- There is a need for effective treatments for inflamed synovium unresponsive to medical management.
Purpose of the Study:
- To evaluate photo-dynamic therapy (PDT) as a minimally invasive method for ablating inflamed synovium.
- To determine the efficacy of a photosensitizer, Haematoporphyrin Derivative (HpD), in targeting inflamed joint tissues.
Main Methods:
- Pharmacokinetic studies of HpD in a rabbit knee arthritis model.
- Intra-articular laser light activation of HpD at varying doses (0-200 J/cm²).
- Histological analysis of synovium and surrounding tissues.
Main Results:
- HpD demonstrated rapid accumulation in inflamed synovium, with a high synovium-to-muscle uptake ratio (22.8).
- Selective ablation of inflamed synovium was achieved at light doses of 100 J/cm² and higher.
- No significant damage was observed in normal intra-articular tissues.
Conclusions:
- HpD selectively accumulates in inflamed synovium.
- PDT with HpD and intra-articular light effectively ablates inflamed synovium.
- PDT shows promise as a novel, selective, and minimally invasive synovectomy technique.
