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

[ Vol. 10 , Issue. 1 ]

Author(s):

Tahereh Firouzyar, Amir Reza Jalilian, Mohammad Reza Aboudzadeh, Hossein Sadeghpour, Mehrban Pooladi, Mahdi Shafiee-Ardestani and Ali Khalaj   Pages 51 - 58 ( 8 )

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.

Affiliation:

Nuclear Medicine and Molecular Imaging Research Center, Namazi Teaching Hospital, Shiraz University of Medical Sciences, Shiraz, Radiation Application Research School, Nuclear Science and Technology Research Institute, Postal code: 141551339 Tehran, Radiation Application Research School, Nuclear Science and Technology Research Institute (NSTRI), Tehran, Radiation Application Research School, Nuclear Science and Technology Research Institute (NSTRI), Tehran, Radiation Application Research School, Nuclear Science and Technology Research Institute (NSTRI), Tehran, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran

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