Preparation and preclinical evaluation of68Ga-DOTA-amlodipine for L-type calcium channel imaging.
OBJECTIVE
In order to develop a possible tracer for L-type calcium channel imaging, we here report the development of a Ga-68 amlodipine derivative for possible PET imaging.


METHODS
Amlodipine DOTA conjugate was synthesized, characterized and went through calcium channel blockade, toxicity, apoptosis/necrosis tests. [68Ga] DOTA AMLO was prepared at optimized conditions followed by stability tests, partition coefficient determination and biodistribution studies using tissue counting and co incidence imaging up to 2 h.


RESULTS
[68Ga] DOTA AMLO was prepared at pH 4-5 in 7-10 min at 95°C in high radiochemical purity (>99%, radio thin layer chromatography; specific activity: 1.9-2.1 GBq/mmol) and was stable up to 4 h with a logPof -0.94. Calcium channel rich tissues including myocardium, and tissues with smooth muscle cells such as colon, intestine, and lungs demonstrated significant uptake. Co incidence images supported the biodistribution data up to 2 h.


CONCLUSIONS
The complex can be a candidate for further positron emission tomography imaging for L type calcium channels.
Nuclear Medicine and Molecular Imaging Research Center, Shiraz University of Medical Science, Shiraz, Iran.
Tahereh
T
Firuzyar
Department of Medicinal Chemistry, Radiation Application Research School, Nuclear Science and Technology Research Institute, Tehran, Iran.
Amir Reza
AR
Jalilian
Department of Medicinal Chemistry, Radiation Application Research School, Nuclear Science and Technology Research Institute, Tehran, Iran.
Mohammad Reza
MR
Aboudzadeh
Department of Medicinal Chemistry, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran.
Hossein
H
Sadeghpour
Nuclear Medicine and Molecular Imaging Research Center, Shiraz University of Medical Science, Shiraz, Iran.
Mahdi
M
Shafiee-Ardestani
Nuclear Medicine and Molecular Imaging Research Center, Shiraz University of Medical Science, Shiraz, Iran.
Ali
A
Khalaj
Amlodipine; Ga-68; apoptosis/necrosis assay; biodistribution; calcium channel blockade activity