Radiosynoviorthesis: A new therapeutic and diagnostic tool for canine joint inflammation
Nigel R. Stevenson, PhD
John M. Donecker, VMD, MS
Convetra, Inc.
Radiosynoviorthesis in clinical practice
A key aspect of RSO is the choice of a radionuclide. Three radionuclides are widely used in clinical practice to treat synovitis: 90Y, rhenium-186 (186Rh), and erbium-169 (169Er), all of which are artificially produced in a nuclear reactor [Ref 2-4]. In the case of RSO treatment, the radionuclide emits radiation that penetrates the outermost layer of the synovial membrane where they produce energy of sufficient duration and intensity to achieve apoptosis and ablation of the inflamed cells. For this to occur, the radionuclide must have an adequate half-life (t½ ), a selective tissue penetration range approximating the synovial thickness, and sufficient energy for therapeutic effect.
As 90Y, 186Rh and 169Er decay, they emit radiation in the form of beta particles with a relatively wide tissue penetration range (Figure 1). While these radionuclides are therapeutically useful and have been evaluated in large clinical trials [Ref 2], their physical properties are not necessarily ideal for RSO. For example, 90Y emits beta radiation that has a relatively wide range of soft tissue penetration, which risks irradiation of adjacent non-synovial tissue. 186Re and 90Y have short halflives (2.7 and 3.7 days respectively), thereby creating storage and logistical limitations but also leading to a risk of not consistently delivering sufficient irradiation at the synovial target site [Ref 5]. 169Er lacks any diagnostic emissions which makes traceability a potential issue
Tin-117m: A novel radionuclide
Tin-117m (117mSn) is a unique radionuclide without the disadvantages of high-energy betaemitting radionuclides (Table 1 compares physical properties of 117mSn with other therapeutic radionuclides) [Ref 6]. As such, 117mSn is particularly well suited for RSO, including in dogs and horses. Instead of high-energy beta particles with a wide tissue penetration range (50-5,000 m), 117mSn emits abundant conversion electrons, low-energy particles with a short, relatively nondiminishing penetration range of approximately 300 m in tissue (Figure 1). Sn-117m has a t½ of nearly 14 days, providing an ideal duration of effect spanning several half-lives to achieve therapeutic results and to enable short-term stability during storage and handling. To illustrate, Figure 2 shows >99% dose retention in the joint of a dog three days following intra-articular injection with homogenous 117mSn colloid (Synovetin OA™) [Ref 7]. No other radionuclide exists, combining the properties of 117mSn [Ref 8].
Figure 1. The diagram compares the radiation dose range of conversion electrons emitted by 117mSn (300 m, green zone) with beta-radiation emitted by radionuclides such as 90Y, 186Re and 169Er (up to 11,000 m, blue zone). The ultra-narrow, discrete radiation range of 117mSn enables more precise dosimetry and avoidance of adverse effects on that beta-emitting radionuclides can have on adjacent tissues.
Due to its unique therapeutic and diagnostic (theranostic) properties as a conversion electron- and gamma-emitter with an optimal t1/2, 117mSn has attracted interest as a radiopharmaceutical and also now as a medical device in the colloid form. Favorable results were reported in clinical trials (phase I and phase II) where 117mSn was used to treat metastatic bone pain in human patients [Ref 9-11]. Investigators noted the value of the gamma emission component of 117mSn, which provides an objective basis for diagnostic monitoring, disease staging, dosage estimates, and assessing response to therapy [Ref 11-12].
Synovetin OA™ - A homogenous colloid of 117mSn
Convetra Inc. has developed a patented preparation of 117mSn specifically for RSO and other potential applications in veterinary and human medicine. 117mSn is manufactured using methods that produce yields sufficient to be scaled up for manufacturing therapeutic dosages in commercial quantities [Ref 8]. The 117mSn radionuclide is combined with a homogenous colloid to form Synovetin OA™, the final injectable product [Ref 8]. The radionuclide particles are small enough to be phagocytized by synovial macrophages but large enough to avoid leakage outside the joint prior to phagocytosis. In situ retention of the Synovetin OA™ in laboratory animals has been measured out to five t½ (i.e., 68 days), a duration sufficient for therapeutic efficacy. Synovetin OA™ has demonstrated safety and efficacy following RSO of experimental OA in rats and dogs and safety in normal canine elbow joints (Figure 3).
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