Towards Topical Quantitation of Striatal Dopamine Tracer Uptake: A Monte Carlo Simulation

Objectives: The reduction of striatal dopamine uptake is linked to the clinical progression of Essential Tremors and Parkinson’s Disease. The current standard of care in patients with early symptoms is to measure striatal uptake using DaTscan™ (GE Healthcare, Ioflupane I-123 Injection), the only US FDA approved agent for evaluation of suspected parkinsonian syndromes using Single Photon Emission Computed Tomography (SPECT) imaging. Previously published work indicates that striatal uptake of [¹²³I]-E-IACFT, an ¹²³I-based dopamine transport radiotracer, is 20+ times higher than the background in healthy individuals. This level of uptake specificity may allow for low-cost, pre-screening measurements of striatal uptake prior to conventional SPECT imaging. To study the feasibility of such an approach, we conducted Monte Carlo simulations to investigate the ability of topical scintillation detectors placed directly on a patient’s scalp to quantify the striatal uptake of ¹²³I.

Methods: Using the GATE Monte Carlo simulation framework and anthropomorphic models of the head, we simulated tungsten-shielded, topical scintillation detectors and striatal uptake of ¹²³I. Simulated uptake included target-to-background concentration ratios ranging from 1:1 (severely decreased striatal uptake) to 20:1 (normal striatal uptake). Simulations were performed for graduated (5% increments) striatal uptake from minimal uptake (5%) to normal uptake (100%). Each simulation was broken into 8 parts using time-slice multiplexing to increase randomness and performed 5 times to calculate average results. Each simulation consisted of 10 seconds of counts integration. Background activity in the brain was held constant for all simulations. Detector output was compared to input concentrations to assess sensitivity to disease state (healthy, Essential Tremor, Parkinson’s Disease).

Results: Detector output ranged from 25 ± 2.6 counts at 5% uptake to 540 ± 28.8 counts for 100% uptake. Output due to background brain activity remained constant at 388 ± 18 counts. The total detector output ranged from 413 ± 15.9 counts to 933 ± 27.2 counts. A simulated reduction in normal striatal uptake of 95% resulted in a 55% reduction in detector output. Conclusion: In order to quantify the 30% reduction in striatal uptake that may be indicative of Essential Tremors, detector output decreases by 16.1%. In order to quantify a 75% reduction, likely indicative of Parkinson’s Disease, detector output decreases by 45.7%. These sensitivity results are promising for the ability of a topical detector to quantify specific striatal uptake. Additionally, topical detectors could provide a dynamic measure of uptake which may prove useful for kinetic analysis of disease state.

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