Design, Synthesis, and Validation of a Novel [11C]Promethazine PET Probe for Imaging Abeta Using Autoradiography

Clayton A Whitmore; Mariam I Boules; William J Behof; Justin R Haynes; Dmitry Koktysh; Adam J Rosenberg; Mohammed N Tantawy; Wellington Pham

doi:10.3390/molecules26082182

Design, Synthesis, and Validation of a Novel [¹¹C]Promethazine PET Probe for Imaging Abeta Using Autoradiography

Molecules. 2021 Apr 10;26(8):2182. doi: 10.3390/molecules26082182.

Authors

Clayton A Whitmore^{1

2}, Mariam I Boules^{1

2}, William J Behof^{1

2}, Justin R Haynes^{1

2}, Dmitry Koktysh^{3

4}, Adam J Rosenberg^{1

2}, Mohammed N Tantawy^{1

2}, Wellington Pham^{1

2

4

5

6

7

8

9

10}

Affiliations

¹ Vanderbilt University Medical Center, Vanderbilt University Institute of Imaging Science, Nashville, TN 37232, USA.
² Department of Radiology and Radiological Sciences, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
³ Department of Chemistry, Vanderbilt University, VU Station, Nashville, TN 37235, USA.
⁴ Vanderbilt Institute of Nanoscale Science and Engineering, Vanderbilt University, Nashville, TN 37235, USA.
⁵ Department of Biomedical Engineering, Vanderbilt University, Nashville, TN 37235, USA.
⁶ Vanderbilt Brain Institute, Vanderbilt University, Nashville, TN 37232, USA.
⁷ Vanderbilt Ingram Cancer Center, Nashville, TN 37232, USA.
⁸ Vanderbilt Institute of Chemical Biology, Vanderbilt University, Nashville, TN 37232, USA.
⁹ Vanderbilt Memory and Alzheimer's Center, Vanderbilt University Medical Center, Nashville, TN 37212, USA.
¹⁰ Institute of Imaging Science, Vanderbilt University, 1161, 21st Avenue South, Nashville, TN 37232, USA.

Abstract

Promethazine, an antihistamine drug used in the clinical treatment of nausea, has been demonstrated the ability to bind Abeta in a transgenic mouse model of Alzheimer's disease. However, so far, all of the studies were performed in vitro using extracted tissues. In this work, we report the design and synthesis of a novel [¹¹C]promethazine PET radioligand for future in vivo studies. The [¹¹C]promethazine was isolated by RP-HPLC with radiochemical purity >95% and molar activity of 48 TBq/mmol. The specificity of the probe was demonstrated using human hippocampal tissues via autoradiography.

Keywords: Abeta; Alzheimer; PET imaging; autoradiography; promethazine.

MeSH terms

Alzheimer Disease / diagnosis*
Alzheimer Disease / diagnostic imaging
Alzheimer Disease / pathology
Animals
Autoradiography
Brain / diagnostic imaging*
Brain / drug effects
Humans
Mice
Plaque, Amyloid / diagnosis
Plaque, Amyloid / diagnostic imaging
Plaque, Amyloid / pathology
Positron-Emission Tomography
Promethazine / chemical synthesis
Promethazine / chemistry
Promethazine / pharmacology*
Radiochemistry
Radiopharmaceuticals / chemical synthesis
Radiopharmaceuticals / chemistry
Radiopharmaceuticals / pharmacology*

Substances

Radiopharmaceuticals
Promethazine

Abstract

MeSH terms

Substances

Grants and funding