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Synthesis, Radiolabeling, and in Vitro and in Vivo Evaluation of [ 18 F]ENL30 : A Potential PET Radiotracer for the 5-HT 7 Receptor

Tampio L'Estrade, Elina; Edgar, Fraser G.; Xiong, Mengfei; Shalgunov, Vladimir; Baerentzen, Simone L.; Erlandsson, Maria; Ohlsson, Tomas G. LU ; Palner, Mikael; Knudsen, Gitte M. and Herth, Matthias M. (2019) In ACS Omega 4(4). p.7344-7353
Abstract


The 5-HT
7
receptor (5-HT
7
R) is involved in a broad range of physiological conditions and disorders. Currently, there is no validated clinical positron emission tomography (PET) tracer available; however, we have recently developed a promising
11
C-labeled candidate. In this... (More)


The 5-HT
7
receptor (5-HT
7
R) is involved in a broad range of physiological conditions and disorders. Currently, there is no validated clinical positron emission tomography (PET) tracer available; however, we have recently developed a promising
11
C-labeled candidate. In this project, we aimed to further extend our efforts and develop an
18
F-labeled derivative, coined [
18
F]ENL30. Fluorine-18 has several advantages over carbon-11 especially within the preclinical phase, where a long half-life usually increases evaluation throughput. ENL30 was successfully synthesized in a low albeit sufficient overall yield. Radiolabeling succeeded with a radiochemical yield of approximately 4.5%. Subsequent preclinical PET studies revealed that [
18
F]ENL30 binds specifically to the 5-HT
7
R but suffered from affinity to σ-receptors. Additionally, we identified [
18
F]ENL30 to be a P-gp substrate in rats. However, we believe that [
18
F]ENL30 may prove to be valuable in higher species that exhibit decreased P-gp dependency. If required, σ-receptor binding could, in such studies, be selectively blocked potentially allowing for selective 5-HT
7
R imaging.

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Please use this url to cite or link to this publication:
author
publishing date
type
Contribution to journal
publication status
published
subject
in
ACS Omega
volume
4
issue
4
pages
10 pages
publisher
American Chemical Society (ACS)
external identifiers
  • scopus:85064980018
ISSN
2470-1343
DOI
10.1021/acsomega.9b00394
language
English
LU publication?
no
id
3354ccfb-0892-4039-bb4e-b27c63880896
date added to LUP
2019-05-15 15:00:25
date last changed
2019-05-15 15:00:25
@article{3354ccfb-0892-4039-bb4e-b27c63880896,
  abstract     = {<p><br>
                                                         The 5-HT                             <br>
                            <sub>7</sub><br>
                                                          receptor (5-HT                             <br>
                            <sub>7</sub><br>
                                                         R) is involved in a broad range of physiological conditions and disorders. Currently, there is no validated clinical positron emission tomography (PET) tracer available; however, we have recently developed a promising                              <br>
                            <sup>11</sup><br>
                                                         C-labeled candidate. In this project, we aimed to further extend our efforts and develop an                              <br>
                            <sup>18</sup><br>
                                                         F-labeled derivative, coined [                             <br>
                            <sup>18</sup><br>
                                                         F]ENL30. Fluorine-18 has several advantages over carbon-11 especially within the preclinical phase, where a long half-life usually increases evaluation throughput. ENL30 was successfully synthesized in a low albeit sufficient overall yield. Radiolabeling succeeded with a radiochemical yield of approximately 4.5%. Subsequent preclinical PET studies revealed that [                             <br>
                            <sup>18</sup><br>
                                                         F]ENL30 binds specifically to the 5-HT                             <br>
                            <sub>7</sub><br>
                                                         R but suffered from affinity to σ-receptors. Additionally, we identified [                             <br>
                            <sup>18</sup><br>
                                                         F]ENL30 to be a P-gp substrate in rats. However, we believe that [                             <br>
                            <sup>18</sup><br>
                                                         F]ENL30 may prove to be valuable in higher species that exhibit decreased P-gp dependency. If required, σ-receptor binding could, in such studies, be selectively blocked potentially allowing for selective 5-HT                             <br>
                            <sub>7</sub><br>
                                                         R imaging.                         <br>
                        </p>},
  author       = {Tampio L'Estrade, Elina and Edgar, Fraser G. and Xiong, Mengfei and Shalgunov, Vladimir and Baerentzen, Simone L. and Erlandsson, Maria and Ohlsson, Tomas G. and Palner, Mikael and Knudsen, Gitte M. and Herth, Matthias M.},
  issn         = {2470-1343},
  language     = {eng},
  number       = {4},
  pages        = {7344--7353},
  publisher    = {American Chemical Society (ACS)},
  series       = {ACS Omega},
  title        = {Synthesis, Radiolabeling, and in Vitro and in Vivo Evaluation of [                         
                        <sup>18</sup>
                                                 F]ENL30 : A Potential PET Radiotracer for the 5-HT                         
                        <sub>7</sub>
                                                  Receptor},
  url          = {http://dx.doi.org/10.1021/acsomega.9b00394},
  volume       = {4},
  year         = {2019},
}