Add time:09/07/2019         Source:sciencedirect.com

The biodistribution has been assessed in mice of synthetic branched polypeptides. These were: A poly(l-lysine) backbone with short side chains of three dl-alanine residues (AK, which is polycationic); AK with an additional glutamic acid residue at the end of the branches (EAK, which is amphoteric); EAK whose terminal glutamic acid amino groups had been acetylated (Ac-EAK, which is polyanionic) or succinylated (Suc-EAK, which is highly polyanionic). Each was labelled with gamma emitting radionuclides suitable for use in biodistribution studies (125I and 51Cr) or for gamma scintigraphy (111In). Regardless of the radiolabel, both EAK and Ac-EAK showed prolonged survival in the blood over a four hour observation period, while polycationic AK or highly polyanionic Suc-EAK were rapidly cleared. There were great differences in organ retention of the different radionuclides from any one polypeptide. With AK there were much higher levels of 51Cr than of 111In or 125I in spleen, liver and lung. With EAK, there were higher levels of 51Cr than of 111In or 125I in liver and spleen, but higher levels of 111In than of 51Cr or 125I in kidney. The pattern was similar with Ac-EAK, but the high kidney level of 111In seen with EAK was not present. With Suc-EAK, biodistribution of 111In and 51Cr were virtually identical with very high levels in spleen and liver, which were not seen with 125I. This study has shown that only amphoteric or mildly anionic polypeptides survive well in the circulation. Cationic or highly anionic polypeptides survive poorly, but have different sites of clearance, the former going particularly to spleen, kidney, liver and lung, the latter particularly to spleen and liver. However the apparent site of clearance depends upon the labelling radionuclide. Presumably, this reflects the handling within organs of the particular radioelement and/or (in the case of radiometals) the amino acids to which its chelating DTPA was covalently linked.

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