TY - JOUR

T1 - Synthesis, Radiolabeling, and in Vitro and in Vivo Evaluation of [18F]ENL30

T2 - A Potential PET Radiotracer for the 5-HT7 Receptor

AU - Tampio L'Estrade, Elina

AU - Edgar, Fraser G.

AU - Xiong, Mengfei

AU - Shalgunov, Vladimir

AU - Baerentzen, Simone L.

AU - Erlandsson, Maria

AU - Ohlsson, Tomas G.

AU - Palner, Mikael

AU - Knudsen, Gitte M.

AU - Herth, Matthias M.

PY - 2019/4/23

Y1 - 2019/4/23

N2 - The 5-HT7 receptor (5-HT7R) 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 11C-labeled candidate. In this project, we aimed to further extend our efforts and develop an 18F-labeled derivative, coined [18F]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 [18F]ENL30 binds specifically to the 5-HT7R but suffered from affinity to σ-receptors. Additionally, we identified [18F]ENL30 to be a P-gp substrate in rats. However, we believe that [18F]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-HT7R imaging.

AB - The 5-HT7 receptor (5-HT7R) 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 11C-labeled candidate. In this project, we aimed to further extend our efforts and develop an 18F-labeled derivative, coined [18F]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 [18F]ENL30 binds specifically to the 5-HT7R but suffered from affinity to σ-receptors. Additionally, we identified [18F]ENL30 to be a P-gp substrate in rats. However, we believe that [18F]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-HT7R imaging.

U2 - 10.1021/acsomega.9b00394

DO - 10.1021/acsomega.9b00394

M3 - Journal article

AN - SCOPUS:85064980018

VL - 4

SP - 7344

EP - 7353

JO - ACS Omega

JF - ACS Omega

SN - 2470-1343

IS - 4

ER -