Synthesis of labelled small peptide complexes for imaging agents with technetium-99m and biodistribution in mice / 药学学报

ABSTRACT

<p><b>AIM</b>To look for new heart or kidney imaging agents. Five new target chelators--2-N-(2'-s-triphenylmethylacetyl) amino-(N'-acetyl glycine) isovalericamide (MVG2), 2-N-(2'-s-triphenylmethylacetyl) amino-[N'-acetyl-(N"-butylacetaminde)] isovalericamide (MVGT), 2-N-(2'-s-tri-phenylmethylacetyl) amino-[N'-acetyl-(N"-cyclohexanylacetaminde)] isovalericamide (MVGH), 2-N-(2'-s-triphenylmethylacetyl) amino-[N'-acetyl-(N"-butylacetaminde)] phenyl propamide (MPGT) and 2-N-(2'-s-triphenylmethylacetyl) amino-[N'-acetyl-(N"-cyclohexanylacetaminde)] phenylpropamide (MPGH) were synthesized as primitive materials to explore the synthetic methods of polypeptides.</p><p><b>METHODS AND RESULTS</b>All target chelators were identified on the basis of the spectroscopic data, such as IR, 1HNMR, 13CNMR and elementary analysis. Different active esters with mercaptoacetic acid as primitive materials were used to explore the biodistribution of Technetium-99m labelling chelators in mice. The chelators were labeled with Technetium-99m and further tested for the biological activity in mice. Values given in ID which is the percentage injected dose per organ was tested to explore new heart imaging agents. The ID was determined in vivo by biodistribution study. Tc-99m complexes 0.1 mL was injected into laterial tail vein of 3 anaesthetised rats. At 2, 5, 10, 30, 60 minutes post-injection, rats were sacrificed by decapitation, bled from the neck and the organs were removed. The radioactivities in various organs were determined in an automatic twin crystal gamma counter. Five new target chelators were labeled with Technetium-99m in high yield (> 95%). The bio-distribution resulted in mice indicate that 99Tcm-MVG2 has high kidney uptake, good retention, quick blood clearance and high activity ratios of kidneys to other tissues. 99Tcm-MVGT, 99Tcm-MVGH and 99Tcm-MPGT have better heart accumulation, but shorter retention, slower blood clearance and lower activity ratios of kidneys to other tissues. They were mainly metabolized through liver and kidney.</p><p><b>CONCLUSION</b>99Tcm-MVG2 will be a new potential renal function imaging agent and 99Tcm-MVGT, 99Tcm-MVGH and 99Tcm-MPGT will be new potential heart function imaging agents if their structure and activity relationships are further studied.</p>