Evaluation of Weight based Dosing Accuracy using Constant Activity and Bolus Infusion Methods using the Jubilant DraxImage Rubidium 82 Elution System

Objectives: The new, recently FDA-approved, Rubidium Elution System from Jubilant DraxImage provides the user with bolus and constant activity methods of tracer delivery. The constant activity infusion mode delivers activity with a square wave profile, which offers more consistent activity profiles and has been shown to improve the test-retest variability of myocardial blood flow (MBF) measurements when compared to constant-flow-rate bolus administration of Rb-82¹. The purpose of this study was to demonstrate the ability of the commercial RUBY-FILL® elution system to consistently and accurately deliver sterile, non-pyrogenic doses of Rb-82 using constant activity and bolus methods of infusion with weight-based dosing (10-60mCi) in a simulated clinical setting.

Methods: Six Rubidium Rb-82 generators (100 mCi) with six separate elution systems were investigated. Prior to simulated patient infusions, a daily setup procedure was performed, which included an automatic calibration of the activity counter (versus the integrated dose calibrator) and Sr-82 limit detection measurements. For the first clinical simulation study, 7-8 fictitious patients were evaluated per infusion system each day for up to eight weeks. Each fictitious patient session consisted of two weight-based, 30 second infusions, representing infusions for a typical rest-stress imaging protocol. The simulated patient infusions were collected using bolus and constant activity modes. Accuracy and precision of delivered dose, infusion volume, flow rate and infusion time were determined. The second clinical simulation study focused on the accuracy of the dose extremes, and > 1200 infusions on both constant activity and bolus infusion modes were evaluated. Sterility and bacterial endotoxin testing was also performed by collecting samples at different time points throughout the shelf-life of the generators. Media-Fill testing was performed at the end of the clinical simulations to address potential development of biofilms.

Results: Acceptance criteria for accuracy and precision of dose, infusion volume, flow rate and infusion duration were met for the >1500 patient infusions. For the second clinical simulation study, all data points were within accuracy acceptance criteria of ≤ 10% within the dose range of 10-60mCi, over the full lifetime of the generator (up to 60 days). RUBY tubing sets designed for dedicated use with the commercial elution system that comprise the drug fluid path were shown to maintain sterility through the entire shelf-life of Generator (i.e. up to 60 days). The excellent accuracy and precision displayed by the Rubidium-82 Elution System during the delivery of the infusions is a result of distinct, key features incorporated, including: A single, highly automated, daily calibration that provides the same accuracy (≤ 10%) for the complete dose range of 10-60 mCi, and a saline flush added at the end of the radioactive infusion that ensures the entire intended dose is administrated into the patient.

Conclusion: Rubidium-82 Elution System consistently and accurately delivers sterile and non-pyrogenic doses of Rb-82 Rubidium Chloride. Simulated clinical testing demonstrated excellent dosing accuracy with weight-based dosing in multiple infusion delivery modes, including constant activity, without a system re-calibration requirement. Reference: ¹Klein Ran, Ocneanu A, Renaud JM et al. Consistent tracer administration profile improves test-retest repeatability of myocardial blood flow quantification with 82Rb dynamic PET imaging. J of Nucl Cardiol; Online first doi:10.1007/s12350-016-0698-6