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

Author(s): Tahereh Firouzyar, Amir Reza Jalilian, Mohammad Reza Aboudzadeh, Hossein Sadeghpour, Mehrban Pooladi, Mahdi Shafiee-Ardestani, Ali Khalaj.

Journal Name: Current Radiopharmaceuticals

Volume 10 , Issue 1 , 2017

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Abstract:

Purpose: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

Keywords: Technetium-99m, amlodipine, Calcium channel blockade activity, apoptosis/necrosis assay, radiolabeling, Biodistribution, SPECT.

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Article Details

VOLUME: 10
ISSUE: 1
Year: 2017
Page: [51 - 58]
Pages: 8
DOI: 10.2174/1874471010666170104115011
Price: $58

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