ALA-induced porphyrin formation and fluorescence in synovitis tissue:

Summary 

The synovial inflammatory process in rheumatoid arthritis (RA) is accompanied by massive tumor-like proliferation and activation of the connective stroma. These abnormal cells actively invade and destroy the peri-articular bone and cartilage at the margins of joints where synovium and bone are attached. There is still a lack of minimally invasive synovectomy methods, which might be suitable for the smaller joints. Unfortunately, these joints are usually involved in the disease. Photodynamic therapy has been evaluated as a possible treatment modality for RA synovitis. The present study describes the differences of 5-aminolevulinic acid (5-ALA) and 5-ALA ester-induced protoporphyrin IX (PpIX) production in cell cultures obtained from patients with RA, osteoarthritis (OA) and human sarcoma cell line (HS 192.T) and in a collagen-induced arthritis model in rats. The incubation of cells with hexyl aminolevulinate (HAL) induced the same amount of fluorescence as 5-ALA and methyl aminolevulinate (MAL) at about a 100-fold lower concentration. Incubation with HAL-induced accumulation of at least twice as much porphyrins in RA- and HS 192.T-cells than 5-ALA and MAL in OA-cells. Similar levels of porphyrins were accumulated in RA and the malignant cells. In vivo, intra-articular application of 5-ALA induced a significant porphyrin accumulation in synovitis tissue as measured by in situ fluorescence spectroscopy. In contrast to our in vitro results and other reports, we could not detect enhanced fluorescence after application of up to 0.1mg HAL.

Abbreviations: 5-ALA, 5-aminolevulinic acid, BPD-MA, benzoporphyrin derivative monoacid ring A, CIA, collagen-induced arthritis, FIA, Freund's incomplete adjuvant, FLS, fibroblast-like synoviocytes, HAL, hexyl aminolevulinate, i.a., intra-articular, MAL, methyl aminolevulinate, OA, osteoarthritis, PBS, phosphate-buffered saline, PDT, photodynamic therapy, PpIX, protoporphyrin IX, RA, rheumatoid arthritis

Keywords: Photodynamic therapy (PDT), Aminolevulinic acid (ALA), Protoporphyrin IX, Fibroblast-like synoviocytes, Synovectomy