99m Tc(CO) 3 -labeled 1-(2-Pyridyl)piperazine derivatives as radioligands for 5-HT 7 receptors.

Autor: Mardanshahi A; Department of Radiology and Nuclear Medicine, Faculty of Medicine, Cardiovascular Research Center, Mazandaran University of Medical Sciences, Sari, Iran., Vaseghi S; Department of Chemistry, Science and Research Branch, Islamic Azad University, Tehran, Iran., Hosseinimehr SJ; Department of Radiopharmacy, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran., Abedi SM; Department of Radiology and Nuclear Medicine, Faculty of Medicine, Cardiovascular Research Center, Mazandaran University of Medical Sciences, Sari, Iran., Molavipordanjani S; Pharmaceutical Sciences Research Center, Hemoglobinopathy Institute, Mazandaran University of Medical Sciences, Sari, Iran. sajjad.molavi@gmail.com.
Jazyk: angličtina
Zdroj: Annals of nuclear medicine [Ann Nucl Med] 2024 Feb; Vol. 38 (2), pp. 139-153. Date of Electronic Publication: 2023 Nov 30.
DOI: 10.1007/s12149-023-01885-2
Abstrakt: Background: The 5-hydroxytryptamine receptor (5-HTR) family includes seven classes of receptors. The 5-HT 7 R is the newest member of this family and contributes to different physiological and pathological processes. As a pathology, glioblastoma multiform (GBM) overexpresses 5-HT 7 R; hence, this study aims to develop radiolabeled aryl piperazine derivatives as 5-HT 7 R imaging agents.  METHODS: Compounds 6 and 7 as 1-(3-nitropyridin-2-yl)piperazine derivatives were radiolabeled with fac-[ 99m Tc(CO) 3 (H 2 O) 3 ] + and 99m Tc(CO) 3 -[6] and 99m Tc(CO) 3 -[7] were obtained with high radiochemical purity (RCP > 94%). The stability of the radiotracers was evaluated in both saline and mouse serum. Specific binding on different cell lines including U-87 MG, MCF-7, SKBR3, and HT-29 was performed. The biodistribution of these radiotracers was evaluated in normal and U-87 MG Xenografted models. Finally, 99m Tc(CO) 3 -[6] and 99m Tc(CO) 3 -[7] were applied for in vivo imaging in U-87 MG Xenografted models.
Results: Specific binding study indicates that 99m Tc(CO) 3 -[6] and 99m Tc(CO) 3 -[7] can recognize 5-HT 7 R of U87-MG cell line. The biodistribution study in normal mice indicates that the brain uptake of 99m Tc(CO) 3 -[6] and 99m Tc(CO) 3 -[7] is the highest at 30 min post-injection (0.8 ± 0.25 and 0.64 ± 0.18%ID/g, respectively). The data of the biodistribution study in the U87-MG xenograft model revealed that these radiotracers could accumulate in the tumor site, and the highest tumor uptake was observed at 60 min post-injection (3.38 ± 0.65 and 3.27 ± 0.5%ID/g, respectively). The injection of pimozide can block the tumor's radiotracer uptake, indicating the binding of these radiotracers to the 5-HT 7 R. The imaging study in the xenograft model also confirms the biodistribution data. The acquired images clearly show the tumor site, and the tumor-to-muscle ratio for 99m Tc(CO) 3 -[6] and 99m Tc(CO) 3 -[7] at 60 min was 3.33 and 3.88, respectively.  CONCLUSIONS: 99m Tc(CO) 3 -[6] and 99m Tc(CO) 3 -[7] can visualize tumor in the U87-MG xenograft model  due to their affinity toward 5-HT 7 R.
(© 2023. The Author(s) under exclusive licence to The Japanese Society of Nuclear Medicine.)
Databáze: MEDLINE
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