Practical Clinical Measurement of Radiotracer Concentration in Blood – Initial Device Concept and Feasibility Testing

Abstract

Kinetic analysis of PET data requires continuous measurement of radioactivity in the arterial blood throughout the acquisition time, termed the arterial input function (AIF). The AIF is used as an input to compartmental modeling, which can be a better predictor of disease progression than SUV measurements from static PET images. Current common methods of measuring blood concentrations include image-derived, population-based, and manual sampling. These all have challenges due to logistical and technological issues as well as patient burden. The aim of this study was to design, develop, and assess a device that is practical and effective for the routine measurement of ß-emitting radiotracer concentration in blood without the drawbacks of current methods and where metabolite analysis is not required. Methods: Designs that integrated a scintillating fiber and a silicon photomultiplier (SiPM) with a general purpose venous access catheter for in vivo measurement were considered. Other design requirements included miniaturization, high sampling rates, and stopping power for ß-particles. Preliminary prototypes were designed to test the feasibility of the concept. Phantom tests were developed to mimic human vasculature. Tests of linearity, sensitivity, signal-to-noise ratios (SNR), the impact of vein diameter, and the influence of gamma radiation were conducted. Results: Prototype sensors were constructed using two different diameters of polystyrene-based scintillating fibers. Fibers were custom polished and fixed to a SiPM. Sensor output was linear with R2 = 0.999 over the range from 0.037 megabecquerels (MBq) per milliliter (mL) to 9.25 MBq/mL. Absolute sensitivity was approximately 450 counts per second (cps) per MBq/mL. Measured SNRs ranged from 1.2:1 to 3.2:1 using a blood to tissue concentration ratio of 1:1. Sensor output increased with vein diameter, and showed no sensitivity to gamma radiation. Conclusion: In experiments with phantom models, the prototype provided accurate measurements of beta-emitting radiotracer concentration. The design will be refined for in vivo testing. The ability to routinely gather blood input function data would facilitate the adoption of kinetic modeling of PET data.