| First Author | Sandhu YK | Year | 2024 |
| Journal | Int J Mol Sci | Volume | 25 |
| Issue | 14 | PubMed ID | 39063132 |
| Mgi Jnum | J:353039 | Mgi Id | MGI:7706766 |
| Doi | 10.3390/ijms25147890 | Citation | Sandhu YK, et al. (2024) [(18)F]Flotaza for Abeta Plaque Diagnostic Imaging: Evaluation in Postmortem Human Alzheimer's Disease Brain Hippocampus and PET/CT Imaging in 5xFAD Transgenic Mice. Int J Mol Sci 25(14) |
| abstractText | The diagnostic value of imaging Abeta plaques in Alzheimer's disease (AD) has accelerated the development of fluorine-18 labeled radiotracers with a longer half-life for easier translation to clinical use. We have developed [(18)F]flotaza, which shows high binding to Abeta plaques in postmortem human AD brain slices with low white matter binding. We report the binding of [(18)F]flotaza in postmortem AD hippocampus compared to cognitively normal (CN) brains and the evaluation of [(18)F]flotaza in transgenic 5xFAD mice expressing Abeta plaques. [(18)F]Flotaza binding was assessed in well-characterized human postmortem brain tissue sections consisting of HP CA1-subiculum (HP CA1-SUB) regions in AD (n = 28; 13 male and 15 female) and CN subjects (n = 32; 16 male and 16 female). Adjacent slices were immunostained with anti-Abeta and analyzed using QuPath. In vitro and in vivo [(18)F]flotaza PET/CT studies were carried out in 5xFAD mice. Post-mortem human brain slices from all AD subjects were positively IHC stained with anti-Abeta. High [(18)F]flotaza binding was measured in the HP CA1-SUB grey matter (GM) regions compared to white matter (WM) of AD subjects with GM/WM > 100 in some subjects. The majority of CN subjects had no decipherable binding. Male AD exhibited greater WM than AD females (AD WMmale symbol/WMfemale symbol > 5; p < 0.001) but no difference amongst CN WM. In vitro studies in 5xFAD mice brain slices exhibited high binding [(18)F]flotaza ratios (>50 versus cerebellum) in the cortex, HP, and thalamus. In vivo, PET [(18)F]flotaza exhibited binding to Abeta plaques in 5xFAD mice with SUVR~1.4. [(18)F]Flotaza is a new Abeta plaque PET imaging agent that exhibited high binding to Abeta plaques in postmortem human AD. Along with the promising results in 5xFAD mice, the translation of [(18)F]flotaza to human PET studies may be worthwhile. |
