title: Development of a Radiolabeled Amlodipine Analog for L-type Calcium Channel Imaging.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Nuclear Medicine and Molecular Imaging Research Center, Namazi Teaching Hospital, Shiraz University of Medical Sciences, Shiraz. Iran.
authors.forename: Tahereh
authors.initials: T
authors.lastname: Firouzyar
authors.affiliation: Radiation Application Research School, Nuclear Science and Technology Research Institute, Postal code: 141551339 Tehran. Iran.
authors.forename: Amir Reza
authors.initials: AR
authors.lastname: Jalilian
authors.affiliation: Radiation Application Research School, Nuclear Science and Technology Research Institute (NSTRI), Tehran. Iran.
authors.forename: Mohammad Reza
authors.initials: MR
authors.lastname: Aboudzadeh
authors.affiliation: Radiation Application Research School, Nuclear Science and Technology Research Institute (NSTRI), Tehran. Iran.
authors.forename: Hossein
authors.initials: H
authors.lastname: Sadeghpour
authors.affiliation: Radiation Application Research School, Nuclear Science and Technology Research Institute (NSTRI), Tehran. Iran.
authors.forename: Mehrban
authors.initials: M
authors.lastname: Pooladi
authors.affiliation: Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran. Iran.
authors.forename: Mahdi
authors.initials: M
authors.lastname: Shafiee-Ardestani
authors.affiliation: Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran. Iran.
authors.forename: Ali
authors.initials: A
authors.lastname: Khalaj
mesh_terms: D017311:Amlodipine / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis; D002121:Calcium Channel Blockers / Q000138:chemical synthesis* / Q000494:pharmacology*; D020746:Calcium Channels, L-Type / Q000378:metabolism*; D002855:Chromatography, Thin Layer; D015394:Molecular Structure; D009336:Necrosis; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000494:pharmacology*; D051381:Rats; D013670:Sodium Pertechnetate Tc 99m / Q000737:chemistry / Q000494:pharmacology; D012997:Solvents / Q000737:chemistry; D014018:Tissue Distribution; D015899:Tomography, Emission-Computed, Single-Photon
chemical_list: D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D019275:Radiopharmaceuticals; D012997:Solvents; D017311:Amlodipine; D013670:Sodium Pertechnetate Tc 99m
keywords: Biodistribution; Calcium channel blockade activity; SPECT; Technetium-99m; amlodipine; apoptosis/necrosis assay; radiolabeling