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

Curr Radiopharm. 2017;10(1):51-58. doi: 10.2174/1874471010666170104115011.

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

MeSH terms

  • 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

Substances

  • Calcium Channel Blockers
  • Calcium Channels, L-Type
  • Radiopharmaceuticals
  • Solvents
  • Amlodipine
  • Sodium Pertechnetate Tc 99m