Dewei Tang1,2, Jun Li3,4,5, Michael L Nickels3,4,5, Gang Huang1,2, Allison S Cohen3,4, H Charles Manning6,7,8,9,10,11,12. 1. Center for Molecular Imaging, Shanghai University of Medicine & Health Sciences, Shanghai, China. 2. Department of Nuclear Medicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 160 Pujian Road, Pudong New District, Shanghai, 200127, China. 3. Vanderbilt University Institute of Imaging Science, Vanderbilt University Medical Center, Nashville, TN, USA. 4. Vanderbilt Center for Molecular Probes (CMP), Vanderbilt University Medical School, 1161 21st Ave. S., AA 1105 MCN, Nashville, TN, 37232-2310, USA. 5. Department of Radiology and Radiological Sciences, Vanderbilt University Medical Center, Nashville, TN, USA. 6. Vanderbilt University Institute of Imaging Science, Vanderbilt University Medical Center, Nashville, TN, USA. henry.c.manning@vanderbilt.edu. 7. Vanderbilt Center for Molecular Probes (CMP), Vanderbilt University Medical School, 1161 21st Ave. S., AA 1105 MCN, Nashville, TN, 37232-2310, USA. henry.c.manning@vanderbilt.edu. 8. Department of Radiology and Radiological Sciences, Vanderbilt University Medical Center, Nashville, TN, USA. henry.c.manning@vanderbilt.edu. 9. Program in Chemical and Physical Biology, Vanderbilt University Medical Center, Nashville, TN, USA. henry.c.manning@vanderbilt.edu. 10. Vanderbilt Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN, USA. henry.c.manning@vanderbilt.edu. 11. Department of Biomedical Engineering, Vanderbilt University, Nashville, TN, USA. henry.c.manning@vanderbilt.edu. 12. Department of Neurosurgery, Vanderbilt University Medical Center, Nashville, TN, USA. henry.c.manning@vanderbilt.edu.
Abstract
PURPOSE: There is an urgent need for the development of novel positron emission tomography (PET) tracers for glioma imaging. In this study, we developed a novel PET probe ([18F]VUIIS1018A) by targeting translocator protein (TSPO), an imaging biomarker for glioma. The purpose of this preclinical study was to evaluate this novel TSPO probe for glioma imaging. PROCEDURES: In this study, we synthesized [19F]VUIIS1018A and the precursor for radiosynthesis of [18F]VUIIS1018A. TSPO binding affinity was confirmed using a radioligand competitive binding assay in C6 glioma cell lysate. Further, dynamic imaging studies were performed in rats using a microPET system. These studies include displacement and blocking studies for ligand reversibility and specificity evaluation, and compartment modeling of PET data for pharmacokinetic parameter measurement using metabolite-corrected arterial input functions and PMOD. RESULTS: Compared to previously reported TSPO tracers including [18F]VUIIS1008 and [18F]DPA-714, the novel tracer [18F]VUIIS1018A demonstrated higher binding affinity and BPND. Pretreatment with the cold analog [19F]VUIIS1018A could partially block tumor accumulation of this novel tracer. Further, compartment modeling of this novel tracer also exhibited a greater tumor-to-background ratio, a higher tumor binding potential and a lower brain binding potential when compared with other TSPO probes, such as [18F]DPA-714 and [18F]VUIIS1008. CONCLUSIONS: These studies illustrate that [18F]VUIIS1018A can serve as a promising TSPO PET tracer for glioma imaging and potentially imaging of other solid tumors.
PURPOSE: There is an urgent need for the development of novel positron emission tomography (PET) tracers for glioma imaging. In this study, we developed a novel PET probe ([18F]VUIIS1018A) by targeting translocator protein (TSPO), an imaging biomarker for glioma. The purpose of this preclinical study was to evaluate this novel TSPO probe for glioma imaging. PROCEDURES: In this study, we synthesized [19F]VUIIS1018A and the precursor for radiosynthesis of [18F]VUIIS1018A. TSPO binding affinity was confirmed using a radioligand competitive binding assay in C6 glioma cell lysate. Further, dynamic imaging studies were performed in rats using a microPET system. These studies include displacement and blocking studies for ligand reversibility and specificity evaluation, and compartment modeling of PET data for pharmacokinetic parameter measurement using metabolite-corrected arterial input functions and PMOD. RESULTS: Compared to previously reported TSPO tracers including [18F]VUIIS1008 and [18F]DPA-714, the novel tracer [18F]VUIIS1018A demonstrated higher binding affinity and BPND. Pretreatment with the cold analog [19F]VUIIS1018A could partially block tumor accumulation of this novel tracer. Further, compartment modeling of this novel tracer also exhibited a greater tumor-to-background ratio, a higher tumor binding potential and a lower brain binding potential when compared with other TSPO probes, such as [18F]DPA-714 and [18F]VUIIS1008. CONCLUSIONS: These studies illustrate that [18F]VUIIS1018A can serve as a promising TSPO PET tracer for glioma imaging and potentially imaging of other solid tumors.
Entities:
Keywords:
Cancer imaging; DPA-714; Glioma; Molecular imaging; PET; TSPO; VUIIS1018A
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