A novel antioxidant ergothioneine PET radioligand for in vivo imaging applications
Abstract Ergothioneine (ERGO) is a rare amino acid mostly found in fungi, including mushrooms, with recognized antioxidant activity to protect tissues from damage by reactive oxygen species (ROS) components. Prior to this publication, the biodistribution of ERGO has been performed solely in vitro us...
Guardado en:
| Autores principales: | , , , , , , , , |
|---|---|
| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
Nature Portfolio
2021
|
| Materias: | |
| Acceso en línea: | https://doaj.org/article/9f1da49055e5462fa3b225a7997b562e |
| Etiquetas: |
Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
|
| id |
oai:doaj.org-article:9f1da49055e5462fa3b225a7997b562e |
|---|---|
| record_format |
dspace |
| spelling |
oai:doaj.org-article:9f1da49055e5462fa3b225a7997b562e2021-12-02T18:02:15ZA novel antioxidant ergothioneine PET radioligand for in vivo imaging applications10.1038/s41598-021-97925-w2045-2322https://doaj.org/article/9f1da49055e5462fa3b225a7997b562e2021-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-97925-whttps://doaj.org/toc/2045-2322Abstract Ergothioneine (ERGO) is a rare amino acid mostly found in fungi, including mushrooms, with recognized antioxidant activity to protect tissues from damage by reactive oxygen species (ROS) components. Prior to this publication, the biodistribution of ERGO has been performed solely in vitro using extracted tissues. The aim of this study was to develop a feasible chemistry for the synthesis of an ERGO PET radioligand, [11C]ERGO, to facilitate in vivo study. The radioligand probe was synthesized with identical structure to ERGO by employing an orthogonal protection/deprotection approach. [11C]methylation of the precursor was performed via [11C]CH3OTf to provide [11C]ERGO radioligand. The [11C]ERGO was isolated by RP-HPLC with a molar activity of 690 TBq/mmol. To demonstrate the biodistribution of the radioligand, we administered approximately 37 MBq/0.1 mL in 5XFAD mice, a mouse model of Alzheimer’s disease via the tail vein. The distribution of ERGO in the brain was monitored using 90-min dynamic PET scans. The delivery and specific retention of [11C]ERGO in an LPS-mediated neuroinflammation mouse model was also demonstrated. For the pharmacokinetic study, the concentration of the compound in the serum started to decrease 10 min after injection while starting to distribute in other peripheral tissues. In particular, a significant amount of the compound was found in the eyes and small intestine. The radioligand was also distributed in several regions of the brain of 5XFAD mice, and the signal remained strong 30 min post-injection. This is the first time the biodistribution of this antioxidant and rare amino acid has been demonstrated in a preclinical mouse model in a highly sensitive and non-invasive manner.William J. BehofClayton A. WhitmoreJustin R. HaynesAdam J. RosenbergMohammed N. TantawyTodd E. PetersonFiona E. HarrisonRobert B. BeelmanWellington PhamNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-11 (2021) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
Medicine R Science Q |
| spellingShingle |
Medicine R Science Q William J. Behof Clayton A. Whitmore Justin R. Haynes Adam J. Rosenberg Mohammed N. Tantawy Todd E. Peterson Fiona E. Harrison Robert B. Beelman Wellington Pham A novel antioxidant ergothioneine PET radioligand for in vivo imaging applications |
| description |
Abstract Ergothioneine (ERGO) is a rare amino acid mostly found in fungi, including mushrooms, with recognized antioxidant activity to protect tissues from damage by reactive oxygen species (ROS) components. Prior to this publication, the biodistribution of ERGO has been performed solely in vitro using extracted tissues. The aim of this study was to develop a feasible chemistry for the synthesis of an ERGO PET radioligand, [11C]ERGO, to facilitate in vivo study. The radioligand probe was synthesized with identical structure to ERGO by employing an orthogonal protection/deprotection approach. [11C]methylation of the precursor was performed via [11C]CH3OTf to provide [11C]ERGO radioligand. The [11C]ERGO was isolated by RP-HPLC with a molar activity of 690 TBq/mmol. To demonstrate the biodistribution of the radioligand, we administered approximately 37 MBq/0.1 mL in 5XFAD mice, a mouse model of Alzheimer’s disease via the tail vein. The distribution of ERGO in the brain was monitored using 90-min dynamic PET scans. The delivery and specific retention of [11C]ERGO in an LPS-mediated neuroinflammation mouse model was also demonstrated. For the pharmacokinetic study, the concentration of the compound in the serum started to decrease 10 min after injection while starting to distribute in other peripheral tissues. In particular, a significant amount of the compound was found in the eyes and small intestine. The radioligand was also distributed in several regions of the brain of 5XFAD mice, and the signal remained strong 30 min post-injection. This is the first time the biodistribution of this antioxidant and rare amino acid has been demonstrated in a preclinical mouse model in a highly sensitive and non-invasive manner. |
| format |
article |
| author |
William J. Behof Clayton A. Whitmore Justin R. Haynes Adam J. Rosenberg Mohammed N. Tantawy Todd E. Peterson Fiona E. Harrison Robert B. Beelman Wellington Pham |
| author_facet |
William J. Behof Clayton A. Whitmore Justin R. Haynes Adam J. Rosenberg Mohammed N. Tantawy Todd E. Peterson Fiona E. Harrison Robert B. Beelman Wellington Pham |
| author_sort |
William J. Behof |
| title |
A novel antioxidant ergothioneine PET radioligand for in vivo imaging applications |
| title_short |
A novel antioxidant ergothioneine PET radioligand for in vivo imaging applications |
| title_full |
A novel antioxidant ergothioneine PET radioligand for in vivo imaging applications |
| title_fullStr |
A novel antioxidant ergothioneine PET radioligand for in vivo imaging applications |
| title_full_unstemmed |
A novel antioxidant ergothioneine PET radioligand for in vivo imaging applications |
| title_sort |
novel antioxidant ergothioneine pet radioligand for in vivo imaging applications |
| publisher |
Nature Portfolio |
| publishDate |
2021 |
| url |
https://doaj.org/article/9f1da49055e5462fa3b225a7997b562e |
| work_keys_str_mv |
AT williamjbehof anovelantioxidantergothioneinepetradioligandforinvivoimagingapplications AT claytonawhitmore anovelantioxidantergothioneinepetradioligandforinvivoimagingapplications AT justinrhaynes anovelantioxidantergothioneinepetradioligandforinvivoimagingapplications AT adamjrosenberg anovelantioxidantergothioneinepetradioligandforinvivoimagingapplications AT mohammedntantawy anovelantioxidantergothioneinepetradioligandforinvivoimagingapplications AT toddepeterson anovelantioxidantergothioneinepetradioligandforinvivoimagingapplications AT fionaeharrison anovelantioxidantergothioneinepetradioligandforinvivoimagingapplications AT robertbbeelman anovelantioxidantergothioneinepetradioligandforinvivoimagingapplications AT wellingtonpham anovelantioxidantergothioneinepetradioligandforinvivoimagingapplications AT williamjbehof novelantioxidantergothioneinepetradioligandforinvivoimagingapplications AT claytonawhitmore novelantioxidantergothioneinepetradioligandforinvivoimagingapplications AT justinrhaynes novelantioxidantergothioneinepetradioligandforinvivoimagingapplications AT adamjrosenberg novelantioxidantergothioneinepetradioligandforinvivoimagingapplications AT mohammedntantawy novelantioxidantergothioneinepetradioligandforinvivoimagingapplications AT toddepeterson novelantioxidantergothioneinepetradioligandforinvivoimagingapplications AT fionaeharrison novelantioxidantergothioneinepetradioligandforinvivoimagingapplications AT robertbbeelman novelantioxidantergothioneinepetradioligandforinvivoimagingapplications AT wellingtonpham novelantioxidantergothioneinepetradioligandforinvivoimagingapplications |
| _version_ |
1718378945035894784 |