The application of samarium-153 particulate hydroxyapatite, a new particulate radiopharmaceutical, for the treatment of chronic synovitis.

摘要

This thesis reports the investigation of a new particulate radiopharmaceutical, samarium-153 particulate hydroxyapatite (Sm-153 PHYP). In the context of current radiation synovectomy practice, the potential use of this new radiopharmaceutical has been evaluated by determining in vitro labelling efficiency and binding stability, optimal intra-articular delivery methods, in vivo biodistribution, safety and short-term clinical efficacy. In vitro Sm-153 labelling of PHYP is efficient. Binding stability is stable under varying physico-chemical conditions similar to those encountered at the time of injection. Activity injection efficiency may be maximised by careful injection technique and by either, reducing the size range of PHYP suspended in saline, or suspending PHYP in sodium hyaluronate. Biodistribution and dosimetry data, derived from serial y scan images of patients treated for chronic knee synovitis with intra-articular Sm-153 PHYP, indicate that treatment is associated with extremely low levels of extra-articular escape of activity and low extra-articular organ doses. Out-patient knee injection appears to be feasible and safe and associated with no observable side effects up to a year following treatment. The particulate radiopharmaceutical is engulfed by synovial tissue soon following injection. Histological examination of synovium, taken from the knee of a patient 3 months after Sm-153 PHYP injection, has shown no evidence of an inflammatory response invoked by PHYP. Sm-153 PHYP knee injection has a favourable impact on symptoms: there was a median response of 9 months in an open prospective study and a trend towards greater efficacy from Sm-153 PHYP compared to intra-articular glucocorticoid injection from an interim analysis of a double-blind randomised controlled study. Radiation synovectomy with Sm-153 PHYP is safe in the short-term and is associated with low levels of extra-articular activity escape and organ doses. There is evidence of a clinical response in the short-term. Sm-153 PHYP is a potentially useful therapy for chronic synovitis.