[18F]VUIIS1009B Features a Superior Imaging Performance to [18F]DPA-714 in TSPO Density Characterization for Neuroinflammatory PET Imaging

Abstract

Purpose: Translocator protein (TSPO), an outer mitochondrial membrane protein, is regarded as a key biomarker for neuroinflammation in a variety of neurodegenerative diseases. In this study, we aim to evaluate two highly specific TSPO radiotracers [18F]VUIIS1009A and [18F]VUIIS1009B in a mild cerebral ischemic rat model, and to compare their in vivo performance to the well-established TSPO probe [18F]DPA-714 for neuroinflammation imaging. With multiple graphic analytical methods tested and macro parameters determined, we propose to find a suitable and best quantification method to profile neuroinflammation and measure TSPO density with the three TSPO radiotracers.Methods: Cerebral ischemia rat model was created and imaged using [18F]VUIIS1009A, [18F]VUIIS1009B and [18F]DPA-714. Displacement studies using non-radioactive analogs were performed to evaluate the binding specificities of [18F]VUIIS1009A and [18F]VUIIS1009B individually. Imaging analysis using arterial plasma input functions (AIFs) was employed to generate Logan plots and parametric images of total distribution volume (VT) for each radiotracer. Reference Logan model using contralateral brain as a reference region was introduced to generate parametric images for binding potential (BPND). Results: When compared to [18F]DPA-714, [18F]VUIIS1009B demonstrated higher binding potential (BPND) and distribution volume ratio (DVR). Parameter images of BPND and VT also indicate [18F]VUIIS1009B has a superior imaging profile with higher BPND and DVR when compared with other two radiotracers in TSPO imaging. Correlation analysis between BPND for [18F]VUIIS1009B and [18F]DPA-714 also indicates [18F]VUIIS1009B is more sensitive than [18F]DPA-714 in TSPO density measurement.Conclusions: This study demonstrates the superiority of [18F]VUIIS1009B to [18F]VUIIS1009A and [18F]DPA-714 in the neuroinflammation imaging. It also demonstrates that [18F]VUIIS1009B PET imaging coupled with parameter mapping (VT and BPND) and graphic analysis using Logan analysis and reference Logan analysis holds great promise for neuroinflammation characterization and TSPO density measurement.