Update and Extension of Release Criteria for Canine 117m Sn Treatments.

ABSTRACT: Tin-117 m ( 117m Sn) is used to treat dogs with osteoarthritic joints by radiosynoviorthesis. The internal conversion and Auger electrons emitted by the 117m Sn provide the therapeutic effect. Sn-117 m also emits x rays and gamma rays, of which the most significant is 158.6 keV. Accurate information regarding the interactions of a person with a treated dog is needed to determine the person's total dose and thus regulatory compliance; i.e., a time and motion study. Prior studies have characterized the radiation field emitted by a treated dog, determined the effective dose rates to a person based on those radiation fields, and evaluated dog-human interactions. These studies have been tied together to calculate the prospective dose to the owner of a treated dog. The behavior modifications needed to comply with public dose limits were identified, and a template for written instructions limiting dose was developed. Further calculations based on the written instructions were made to determine the necessary duration of the instructions. The result is guidance that may be used by veterinary practitioners to release treated dogs in accordance with the public dose limits.

Safety and Clinical Response Following a Repeat Intraarticular Injection of Tin-117m (117mSn) Colloid in Dogs with Elbow Osteoarthritis.

OBJECTIVE: To determine if a repeat intraarticular (IA) injection of a tin-117m colloid radiosynoviorthesis (RSO) agent can be safely given in the same joint 12 months after an initial injection for treatment of canine elbow osteoarthritis (OA), and to evaluate the pain reduction effect of the repeat injection. METHODS AND MATERIALS: Nine client owned dogs with grade 1 or 2 elbow OA were given an IA injection of tin-117m colloid in both elbows, one of which had been treated ≤12 months earlier with the same RSO device. Treatment safety was evaluated by joint fluid analysis at baseline (BL) and at 180 days after treatment, and by urinalysis, CBC, and serum chemistry analysis of diagnostic samples obtained at BL and 180 days. Radiographs, computed tomography, and MRI scans were obtained at BL and 180 days to determine if disease progression differed in elbows given one versus two injections. Clinical response to treatment was assessed subjectively by dog owner responses to the Canine Brief Pain Inventory (CBPI) survey at BL, 90 and 180 days, and objectively by investigator-conducted force plate (FP) analysis of dogs at BL, 90, and 180 days. RESULTS: All post-treatment urinalysis, CBC and clinical chemistry results were within normal ranges. Joint fluid analysis showed a significant (P=0.0411) reduction in the percentage of monocytes at 180 days, consistent with the tin-117m colloid mode of action of apoptosis of pro-inflammatory macrophages at the injection site. There was no significant difference in OA progression in elbows given one or two injections. The treatment success rate was 55.5% (5/9) on day 90 as determined either by CBPI responses or FP analysis, and 66.6% (6/9) on day 180 as determined by FP analysis. CONCLUSION: The tin-117m colloid can be safely given as a repeat injection 12 months after an initial injection, and can potentially provide a durable therapeutic response in dogs with elbow OA.

Anisotropy of the Radiation Field Following Canine Sn-117m Treatment.

ABSTRACT: Tin-117m (117mSn) is used to treated dogs with osteoarthritic joints by radiosynoviorthesis. The internal conversion and Auger electrons emitted by the 117mSn provide the therapeutic effect. Sn-117m also emits gamma rays, of which the most significant is 158.6 keV. The external radiation field around a treated dog is of interest to limit the dose to the owners/caretakers of the dog. The dog's torso attenuates the radiation being emitted toward the opposite side of the dog's body. This leads to a radiation field that is significantly non-isotropic. This study characterizes the anisotropy of this field to permit maximum dose rate measurements to be used to calculate the dose to individuals in the vicinity of the dog. Measurements were made in nine directions and at two distances, 0.3 and 1.0 m, to characterize common distances and spatial orientations for human-dog interactions. From these measurements, the percent reduction in the average dose rate compared to the maximum dose rate was determined. From a radiation safety perspective, the important factor is the minimum amount of shielding effectiveness or percent reduction that can be expected. A reasonable measure for this value is the fifth percentile of the shielding effectiveness distribution. The fifth percentile shielding effectiveness measures are 27% and 21% at 0.3 and 1.0 m, respectively.

Treatment response in dogs with naturally occurring grade 3 elbow osteoarthritis following intra-articular injection of 117mSn (tin) colloid.

The radionuclide 117mSn (tin-117m) embedded in a homogeneous colloid is a novel radiosynoviorthesis (RSO) device for intra-articular (IA) administration to treat synovial inflammation and mitigate osteoarthritis (OA) in dogs. A study to evaluate tin-117m colloid treatment response in dogs with OA was conducted at two centers, the School of Veterinary Medicine at Louisiana State University, and at a referral practice in Houston, Texas. The tin-117m colloid was administered per-protocol to 14 client-owned dogs with radiographically confirmed, grade 3 OA in one or both elbow joints. Dog owners and attending clinicians assessed the level of pain at baseline (BL) and the post-treatment pain response at 90-day intervals for one year. Owners assessed treatment response according to a pain severity score (PSS) and a pain interference score (PIS) as defined by the Canine Brief Pain Inventory. Clinicians reported a lameness score using a 0-5 scale, from no lameness to continuous non-weight bearing lameness, when observing dogs at a walk and a trot. The rate of treatment success as determined by improved mean PSS and PIS scores reported by dog owners was >70% at all time points. Clinicians reported an improved mean pain score from BL at post-treatment Days 90 (p<0.05), 180, and 270. The dog owner and clinician assessments of treatment success were significantly correlated (p>0.05) at Day 90 and Day 180 time points. Results indicated that a single IA dose of tin-117m colloid provided a significant reduction in pain and lameness and improved functionality for up to a full year, with no adverse treatment related effects, in a high percentage of dogs with advanced, clinical OA of the elbow joint.

A model for the development and growth of the parasitic stages of Parascaris spp. in the horse.

Literature documenting the growth and development of Parascaris spp. infections was used to develop a model describing worm dynamics in the young horse. The model incorporates four main variables; the rate at which larvae migrate through host tissues to return to the small intestine, the proportion of migrating larvae which succeed in returning to the small intestine, the rate of growth in size of maturing and adult worms and the survival rate of maturing and adult worms. In addition, the number of eggs laid each day by adult female worms is calculated as a function of worm size (length) and is used to calculate faecal egg output of the foal. Published data describing the rate of migration through host tissues, and the growth of worms following their return to the small intestine, was used to derive relationships describing these processes. However, only limited data exists relating the survival of migrating larvae and mature worms in the intestine to host age and experience of infection. Therefore, relationships and coefficients describing these variables were modified so that output aligned with published experimental results. As a consequence, the model has not yet been evaluated against an independent data set, and so remains as the best 'current hypothesis' for the dynamics of this parasite. Hopefully, future experiments designed to test specific assumptions and outputs of the model will lead to a better understanding of the biology of this important parasite. For example, the most influential variable in determining model output is the survival rate of worms in the small intestine. In the model, worm survival declines in response to both the increasing age of the horse and the increasing cumulative length of worms in the intestine (used as a proxy for crowding). Given the importance of this variable to model behaviour and the paucity of experimental data on this topic this would seem a priority for future study. Initial experiments using the model suggest that a single anthelmintic treatment, administered soon after patency of initial infection, may effectively control environmental contamination with Parascaris spp. eggs while allowing a small 'refugia' of susceptibility to delay the emergence of anthelmintic resistance. Further evaluations of the practicality of this approach may be worthwhile.

Objective evaluation of two deworming regimens in young Thoroughbreds using parasitological and performance parameters.

Parasitic helminths of equids are capable of causing ill-thrift, clinical disease, and death. Although young horses are the most susceptible to parasitic disease and are the most intensively treated cohort, deworming regimens are rarely evaluated within this age group. This study objectively evaluated the impact of deworming regimen on fecal egg counts (FECs), growth rates, and body-condition scores in young Thoroughbreds. Forty-eight Thoroughbred foals from three central Kentucky farms were randomly allocated to two treatment groups: an interval dose program receiving bi-monthly rotations of pyrantel pamoate and ivermectin and a daily deworming group receiving daily rations of pyrantel tartrate feed additive throughout the study, oxibendazole at two months of age, and moxidectin treatments at 9.5 and 16.5 months of age. Pre- and post-treatment eggs per gram of feces (EPGs) of Parascaris spp. and strongyle family parasites, gel/paste dewormer efficacies, and monthly weights and body condition scores were collected. Ascarid and strongyle FECs were not significantly different between groups but were significantly influenced by horse age with strongyle counts continually increasing and ascarid counts peaking at 4.5 months of age. Reduced strongyle efficacies of ivermectin and moxidectin were observed on two farms with consistently low pyrantel pamoate efficacies on all three farms. Ivermectin also exhibited reduced ascarid efficacy. Average daily gain did not differ significantly between groups and was only significantly influenced by age, mirroring average daily gain reference data for Kentucky Thoroughbreds born in 2013. Body condition scores also did not differ between groups, remaining in the optimal range (5-6) for the duration of the study. Management practices resulting in growth rates matching the reference data and in optimal body condition scores compensate for the negative impacts of parasitism even in cases of reduced drug efficacy. Performance parameters can provide useful information in cases of suboptimal parasite control.

A model for the dynamics of the free-living stages of equine cyathostomins.

Anthelmintic resistance in strongyle nematode parasites of horses is an expanding global problem and steps need to be taken to slow its development before control becomes more problematic. A move away from traditional deworming programmes, involving frequent whole-herd treatments with broad spectrum anthelmintics, to a more strategic or targeted use of chemicals is required. However, anthelmintic resistance management strategies which also maintain effective control are invariably more complicated and often require a greater understanding of both nematode epidemiology and grazing management, than does the simple routine use of chemicals. Here, as a first step in applying a modelling approach to resistance management in horses, a model is proposed to describe the dynamics on pasture of the free-living stages of equine cyathostomins. Firstly, the development and survival of the pre-infective stages is considered as a single process driven by temperature, and secondly, two populations of infective stage larvae (L3) are considered; those within the faecal pat and those on the herbage. Both are modelled using the box-car train approach which allows for variable development rates within a cohort of individuals and full overlap of generations. Uniquely, L3 survival is modelled as an ageing process where larvae progress through physiological age classes at a rate determined by temperature and rainfall. Model output reflects the dynamics of free-living stages under a range of environments. Under extreme cold, there is no development to L3 but eggs can survive for long periods to develop if conditions become favourable, while L3 survival is reduced under repeated freeze-thaw cycles. Under tropical conditions, development is rapid and a large number of L3 can be produced but survival of L3 is short. In temperate climates development tends to be slower, with large numbers of L3 produced over the warmer months but fewer over winter, and L3 survival tends to be higher all year round. Although attempts to validate model output against field studies were compromised by the lack of published detail or an inability to access specific weather records, outputs averaged over multiple sets of weather data was often appropriate for that location. Variation in model output when using weather data sets which started on different days within the same week suggests that day-to-day differences in weather may affect the number of L3 developing on pasture and that optimisation of anthelmintic use to minimise pasture infectivity may require a more detailed understanding of weather effects than previously thought.