Synovial ablation in a rabbit rheumatoid arthritis model using photodynamic therapy.
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.


CONCLUSIONS
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.
University of Melbourne Department of Surgery, Royal Melbourne Hospital, Melbourne, Victoria, Australia. adbeisch@netspace.net.au
Andrew D
AD
Beischer
Prithi
P
Bhathal
Richard
R
de Steiger
David
D
Penn
Stan
S
Stylli
D000818:Animals; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D017324:Hematoporphyrin Derivative / Q000493:pharmacokinetics / Q000627:therapeutic use*; D007719:Knee Joint; D023421:Models, Animal; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D011817:Rabbits; D013585:Synovitis / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D014018:Tissue Distribution
D017319:Photosensitizing Agents; D017324:Hematoporphyrin Derivative