Radiosynovectomy of Painful Synovitis of Knee Joints Due to Rheumatoid Arthritis by Intra-Articular Administration of 177 Lu-Labeled Hydroxyapatite Particulates: First Human Study and Initial Indian Experience

Abstract

The aim of this study is to assess the effectiveness of Radiosynovectomy (RSV) using 177Lu-labeled hydroxyapatite (177Lu-HA) in the treatment of painful synovitis and recurrent joint effusion of knee joints in rheumatoid arthritis (RA). Ten patients, diagnosed with RA and suffering from chronic painful resistant synovitis of the knee joints were referred for RSV. The joints were treated with 333 ± 46 MBq of 177Lu-HA particles administered intra-articularly. Monitoring of activity distribution was performed by static imaging of knee joint and whole-body gamma imaging. The patients were evaluated clinically before RSV and at 6 months after the treatment by considering the pain improvement from baseline values in terms of a 100-point visual analog scale (VAS), the improvement of knee flexibility and the pain remission during the night. RSV response was classified as poor (VAS < 25), fair (VAS ≥ 25-50), good (VAS ≥ 50-75) and excellent (VAS ≥ 75), with excellent and good results considered to be success, while fair and poor as failure and also by range of motion. Three phase bone scan (BS) was repeated after 6 months and changes in the second phase of BS3 were assessed visually, using a four-degree scale and in the third phase, semiquantitatively with J/B ratio to see the response. Biochemical analysis of C-reactive protein (CRP) and fibrinogen was repeated after 48 h, 4 and 24 weeks. In all 10 patients, no leakage of administered activity to nontarget organs was visible in the whole-body scan. Static scans of the joint at 1 month revealed complete retention of 177Lu-HA in the joints. All patients showed decreased joint swelling and pains, resulting in increased joint motion after 6 months. The percentage of VAS improvement from baseline values was 79.5 ± 20.0% 6 months after RS and found to be significantly related to patients' age (P = 0.01) and duration of the disease (P = 0.03). Knees with Steinbrocker's Grades 0 and I responded better than those with more advanced changes (Steinbrocker's Grades III and IV) in terms of VAS improvement (75% vs. 45.8%) (P < 0.001). The overall success rate (VAS ≥ 50) was 80%. Remission of pain during the night was achieved in 100%, and knee flexibility was improved in 80%. The changes in the blood pool phase before RSV were 3.2 ± 0.7 and after the therapy 1.4 ± 0.7 (P < 0.001). The J/B ratio was: Before RSV 2.4 ± 0.3; after treatment 1.0 ± 0.2 (P < 0.05). CRP concentration 4 and 24 weeks after the therapy was significantly lower than before treatment. The fibrinogen level was not different before and after RSV. RSV side-effects assessed for the whole follow-up period were minor and not significant. RSV with 177Lu-HA was safe and effective in patients with knee joint chronic painful synovitis of rheumatoid origin. It exhibited significant therapeutic effect after 6 months follow-up period with no significant side-effects. The preliminary investigations reveal that 177Lu-labeled HA particles hold considerable promise as a cost-effective agent for RSV. More elaborate and controlled cl...

Nanoparticulate formulations of radiopharmaceuticals: Strategy to improve targeting and biodistribution properties

“…The first case report was described by Kamaleshwaran et al, in which 90 Y‐HA was injected at knee joint for treatment of villonodular synovitis (PVNS) 155 . Further, Shinto et al used 177 Lu‐labelled HA for treatment of chronic synovitis and rheumatoid arthritis 156 . HA‐conjugated 153 Sm was used for the treatment of knee synovectomy in haemophilia patients 157 .…”

Energy Conversion-Based Nanotherapy for Rheumatoid Arthritis Treatment

“…Radioactive decay transfers radiant energy to the synovial tissue, which gradually causes fibrosis of the synovial tissue, thereby reducing blood perfusion and effusion of inflammatory joints to reduce the infiltration of inflammatory cells (Ahmad and Nisar, 2018 ). Given that the nuclides used to treat arthritis are mostly short-range beta radiation (within a distance of 10 mm), the radiation exposure outside the joint is very low (Kamaleshwaran et al, 2015 ; Shinto et al, 2015 ). Studies have demonstrated that RSV has a relief effect in 60–80% of RA patients (Karavida and Notopoulos, 2010 ).…”

An overview of nanoscale radionuclides and radiolabeled nanomaterials commonly used for nuclear molecular imaging and therapeutic functions

“…First human study and initial Indian experience in the treatment of painful synovitis and recurrent joint effusion of knee joints in rheumatoid arthritis using 177 Lu-labeled HA was reported by Shinto and coworkers. 86 Formerly, preparation and preliminary biological evaluation of 177 Lu-labeled HA as a promising agent for radiation synovectomy of small joints was described by Chakraborty and co-workers. 87 The use of 153 Sm-HA for knee synovectomy in hemophilia was reported by Calegaro et al 88,89 Effectiveness of radiation synovectomy with 90 Y and 153 Sm particulate hydroxyapatite in rheumatoid arthritis patients with knee synovitis was reported by dos Santos and co-workers.…”

“…For example, McDevittand co-workers 194 synthesized 86 Y-CNT construct from amine-functionalized, water-soluble CNT by covalently attaching multiple copies of DOTA chelates and then radiolabeled with the positron-emitting metal-ion, yttrium-86. The whole-body distribution and clearance of 86 Y were characterized at 3 and 24 h postinjection using PET. The yttrium-86 cleared the blood within 3 h and distributed predominantly to the kidneys, liver, spleen, and bone.…”

“…Davarpanah et al optimized fundamental parameters in routine production of 90 Y‐HA for radiosynovectomy. First human study and initial Indian experience in the treatment of painful synovitis and recurrent joint effusion of knee joints in rheumatoid arthritis using 177 Lu‐labeled HA was reported by Shinto and co‐workers . Formerly, preparation and preliminary biological evaluation of 177 Lu‐labeled HA as a promising agent for radiation synovectomy of small joints was described by Chakraborty and co‐workers .…”