Development of a Radiolabeled Amlodipine Analog for L-type Calcium Channel Imaging

The non-invasive imaging and quantification of L-type calcium channels (also known as dihydropyridine channels) in living tissues is of great interest in diagnosis of congestive heart failure, myocardial hypertrophy, irritable bowel syndrome etc. Technetium-99m labeled amlodipine conjugate ([99mTc]-...

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Bibliographic Details
Published in:	Current radiopharmaceuticals Vol. 10; no. 1; p. 51
Main Authors:	Firouzyar, Tahereh, Jalilian, Amir Reza, Aboudzadeh, Mohammad Reza, Sadeghpour, Hossein, Pooladi, Mehrban, Shafiee-Ardestani, Mahdi, Khalaj, Ali
Format:	Journal Article
Language:	English
Published:	United Arab Emirates 01-04-2017
Subjects:	Amlodipine - pharmacology Animals Apoptosis Calcium Channel Blockers - chemical synthesis Calcium Channel Blockers - pharmacology Calcium Channels, L-Type - metabolism Chromatography, Thin Layer Molecular Structure Necrosis Radiopharmaceuticals - chemical synthesis Radiopharmaceuticals - pharmacology Rats Sodium Pertechnetate Tc 99m - chemistry Sodium Pertechnetate Tc 99m - pharmacology Solvents - chemistry Tissue Distribution Tomography, Emission-Computed, Single-Photon Calcium channel blockade activity apoptosis/necrosis assay radiolabeling Biodistribution SPECT Technetium-99m amlodipine
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Summary:	The non-invasive imaging and quantification of L-type calcium channels (also known as dihydropyridine channels) in living tissues is of great interest in diagnosis of congestive heart failure, myocardial hypertrophy, irritable bowel syndrome etc. Technetium-99m labeled amlodipine conjugate ([99mTc]-DTPA-AMLO) was prepared starting freshly eluted (<1 h) 99mTechnetium pertechnetate (86.5 MBq) and conjugated DTPAAMLO at pH 5 in 30 min at room temperature in high radiochemical purity (>99%, RTLC; specific activity: 55-60 GBq/mmol). The calcium channel blockade activity (CCBA) and apoptosis/necrosis assay of DTPA-amlodipine conjugate evaluations were performed for the conjugate. Log P, stability, bio-distribution and imaging studies were performed for the tracer followed by biodistribution studies as well as imaging. The conjugate demonstrated low toxicity on MCF-7 cells and CCBA (at µm level) compared to the amlodipine. The tracer was stable up to 4 h in final production and presence of human serum and log P (-0.49) was consistent with a water soluble complex. The tracer was excreted through kidneys and liver as expected for dihydropyridines; excluding excretory organs, calcium channel rich smooth muscle cells; including colon, intestine and lungs which demonstrated significant uptake. SPECT images supported the bio-distribution data up to 4 h. significant uptake of [99mTc]-DTPA-AMLO was obtained in calcium channel rich organs. The complex can be a candidate for further SPECT imaging for L-type calcium channels.
ISSN:	1874-4729
DOI:	10.2174/1874471010666170104115011