Previous animal studies have established that the
intra-articular injection of holmium-166-chitosan complex (DW-166HC) causes effective
necrosis of the inflamed synovium with litle leakage of radioactivity from the injected joint. Based on these findings, we conducted a phase I/IIa study to examine the biodistribution of
DW-166HC and to assess the safety of
DW-166HC for the treatment of knee
synovitis in patients with
rheumatoid arthritis (RA). A total of 16 patients [1 man, 15 women; median age 49 (range 36-65) years] who had RA knee
synovitis refractory to disease-modifying
anti-rheumatic drug treatments of > 3 months' duration were randomly assigned to three treatment groups with different radiation doses of
DW-166HC: 370 MBq (n = 6), 555 MBq (n = 5) and 740 MBq (n = 5). In each treatment
group, blood and urine radioactivity were analysed by beta counter and biodistribution of the injected
DW-166HC was evaluated using a gamma scan camera. Clinical assessment was done according to three variables (evaluation method): knee joint
pain (visual analogue scale), range of motion (goniometry) and joint swelling (circumference of knee joint). The duration of follow-up observation was 3 months. Following the
intra-articular injection of
DW-166HC, the blood radioactivity was little changed from the baseline measurement and the accumulated radioactivity excreted in urine was minimal. Gamma scan study indicated that most of the injected radiochemical was localized within the injected joint cavity, and the extra-articular leakage was negligible at 24 h after the injection: brain, 0.3%; lung, 0.6%; abdomen, 0.7%; and pelvis, 0.8%. Major adverse events were transient post-injection knee joint
pain and swelling. These results suggest that
DW-166HC might be a safe agent for radiation
synovectomy, particularly for the treatment of knee
synovitis of RA, and further trials in a larger patient population are warranted to evaluate the therapeutic efficacy of
DW-166HC.