Synthesis of new N3S pseudo-peptide complexes and biodistribution in mice / 药学学报

ABSTRACT

<p><b>AIM</b>To explore the synthetic methods of polypeptides containing new heart of kidney imaging agents.</p><p><b>METHODS AND RESULTS</b>Five new target chelators--2-N-(2'-s-triphenylmethylacetyl) amino-(N'-2"-N",N"-diethylethylamine) phenylpropamide (MPNE), 2-N-(2'-s-triphenylmethyl acetyl) amino-(N'-2"-N",N"-dimethylethylamine) phenylpropamide (MPNM), 2-N-(2's-triphenylmethylacetyl) amino-3-methyl-(N'-2"-N",N"-dimethylethylamine) butyramide (MVNM), 2-N-(2'-s-triphenyl methylacetyl) amino-3-methyl-(N'-2"-N",N"-diethylethylamine) butyramide (MVNE), 2-N-(2'-s-triphenylmethylacetyl) amino-(N'-acetylglycine) phenylpropamide (MPG2)--were synthesized through five steps with mercaptoacetic acid as primitive materials, all of which were identified on the basis of spectroscopic data, such as IR, 1HNMR, MS or elementary analysis. The protection of the mercapto group was improved and the relatively new reaction condition of active ester with amino acid is developed. All the chelators were labeled with Technetium-99m and their biological activities in mice given in ID values was tested to explore new heart imaging agents, where ID is the percentage injected dose per organ. The ID was determined by in vivo biodistribution study. Tc-99m complexes 0.1 mL was injected into the laterial tail vein of 3 anaesthetised rats. At 2, 5, 10, 30, 60 min post-injection, rats were sacrificed by decapitation, bled from the neck and dissected. Organs were removed at dissection. The radioactivities in various organs were determined in an automatic twin crystal gamma counter.</p><p><b>CONCLUSION</b>The bio-distribution results in mice indicate that 99Tcm-MVNM have higher heart uptake (ID = 8.40%/g, 2 min post-injection) and quicker blood clearance (ID = 4.3%/g, 60 min post-injection); 99Tcm-MPNE and 99Tcm-MPNM also have fairly high heart uptake and quick blood clearance; 99Tcm-MPG2 has better kidney accumulation and higher activity ratios of kidney to blood (about 4).</p>