Evaluation of the density of presynaptic dopamine Tranporters in humans: development and evaluation of quantitation protocols based on the hybrid SPECT-CT technology using 99mTc-TRODAT-1

• Grant number: 13/25987-2
• Support type: Regular Research Grants
• Duration: November 01, 2014 - April 30, 2017
• Field of knowledge: Health Sciences - Medicine - Medical Radiology
• Principal Investigator: Lauro Wichert Ana
• Grantee: Lauro Wichert Ana
• Home Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated grant(s): 15/50089-3 - Correlation with different clinical stages in patients with Parkinson's disease and neuropathic pain: validation of the Rotterdam Elderly Pain Observation Scale (REPOS), AP.R SPRINT

Abstract

The Parkinson's Disease is a progressive degenerative disorder that affects the compact nigral substance as well as other brain regions. Particularly, the dopamine transporters (DAT) have vital roles in dopaminergic functions by regulating the amount of this neurotransmitter in the synaptic cleft. The [99mTc]-TRODAT-1 is a dopaminergic biomarker which can be used in the investigation of diseases that occur with deficits in this system, such as Parkinson's disease (PD). The hybrid image by SPECT-CT can increase reliability in processing quantitative of the DAT's density with [99mTc ]-TRODAT-1 and increase the diagnostic accuracy of the method, to allow the correction of non-uniform attenuation of photons through the X-rays. This project intends to evaluate different techniques and software for acquisition of SPECT-CT [99mTc ]-TRODAT-1, comparatively with [99mTc]-ECD for processing and quantification of the images, comparing 3 groups of volunteers: normal, mild and advanced PD. As pathophysiological research, we aimed to assess temporal correlation between changes in perfusion with 99mTc -ECD and DAT's density with 99mTc-TRODAT-1 in PD. And as technologic research, we aimed to define a capable protocol and easy to use by most centers of nuclear medicine, reproducible intra and intersubject and accurately validated through physical and clinical tools. OBJECTIVES: (a) To correlate, qualitatively and quantitatively, the images of DAT's density with SPECT [99mTc]-TRODAT-1 with cerebral perfusion with SPECT [99mTc]-ECD; (b) To correlate the SPECT-CT with [99mTc]-TRODAT-1 in healthy volunteers with patients with mild and advanced PD, determining a quantitative threshold between normality and disease; (c) To determine the Sensitivity, Specificity, Positive Predictive Value, Negative Predictive Values and Accuracy of different methods of quantification in the Phantom of Hoffman (physics validation) and in the SPECT-CT with [99mTc]-TRODAT-1 (clinical validation); (d) To compare qualitative and quantitatively the uniform (Chang) and non-uniform (CT) techniques for attenuation correction of photons on the SPECT-CT with [99mTc]-TRODAT-1; (e) To compare the methods OSEM and FBP reconstruction of tomographic images and its effect on the SPECT-CT with [99mTc]-TRODAT-1. (f) To evaluate the inter and intra-subject reproducibility in the quantification of DAT's density in the corpus striatum through the brain SPECT with [99mTc]-TRODAT-1 and using the simulator (phantom). METHODS: We will included 20 healthy volunteers paired with 20 patients with mild PD and 20 with advanced disease. All will be submitted to SPECT-CT with [99mTc]-TRODAT-1 to assess dopamine transporter and SPECT with [99mTc]-ECD to assess the regional Cerebral Blood Flow (rCBF) at rest. The Corpus striatum will be segmented and quantified in images of [99mTc]-TRODAT-1, compared to this data with a reference region (Occipital lobe or cerebellum) and comparing the rCBF. Different techniques and softwares will be used for quantification, segmentation and image processing, including the comparison between EBW/Philips vs. OsiriX vs. ANALYZE©. OUTCOMES: (1) We expect to propose an optimized protocol for the acquisition of SPECT-CT with [99mTc]-TRODAT-1, (2) A definition of the best computational tools for quantification of dopamine transporters SPECT-CT with [99mTc]-TRODAT-1, (3) 1 doctorate orientation completed or already qualified, (4) 2 orientations of master's degree already completed, (5) 1 orientation undergraduates already completed, (6) Minimum of 4 articles submitted or published in national and international periodics , (7) Minimum of 4 papers presented at national and international conferences. (AU)