Improving the blood clearance time of 125I labeled Dex-g-PMAGGCONHTyr by copolymerization

Abstract

Dextran graft copolymers, including dextran graft poly(N-methacryloylglycylglycine) copolymers conjugated with polyethylene glycol and tyrosine (Dex-g-PMAGGCONHPEG_3k-NHTyr), dextran graft poly(N-(2-hydroxypropyl) methacrylamide-co-N-methacryloylglycylglycine)-tyrosine conjugates (Dex-g-P(HPMA-co-MAGGCONHTyr)), and dextran graft poly(methacrylpolyethylene glycol-co-N-methacryloylglycylglycine)-tyrosine conjugates (Dex-g-P(MPEG-co-MAGGCONHTyr)) were synthesized for the purpose to improve the biodistribution and blood clearance time of ploy(N-methacryloylglycylglycine)-tyrosine conjugates (Dex-g-PMAGGCONHTyr). Dynamic light scattering (DLS) results indicated that no aggregation formed in 0.9% saline solution. The graft copolymers were labeled with ¹²⁵I and the labeled copolymers are stable in 0.9% saline and 1% BSA of PBS solutions. Pharmacokinetics studies showed that ¹²⁵I labeled graft copolymer Dex-g-P(HPMA-co-MAGGCONHTyr) had a longer blood clearance time than the others. Biodistribution images confirmed the preferable liver and spleen accumulation at 1 h after injection, and especially for blood tissue, the mean %ID/g value of the PHPMA-modified graft copolymer Dex-g-P(HPMA-co-MAGGCONHTyr) is 7 folds higher than that of Dex-g-PMAGGCONHTyr.