A solid-phase technique for preparation of no-carrier-added technetium-99m radiopharmaceuticals: application to the...

A high effective specific activity (HESA) formulation of a biotin-containing (99m)Tc ligand [RP488: dimethyl-Gly-Ser-Cys(Acm)-Lys(Biotin)-Gly] conveniently prepared from solid phase was compared to a typical low effective specific activity (LESA) solution formulation to demonstrate improved targeting to streptavidin in an in vitro assay and in an in vivo rat model. RP488 was coupled to a maleimide-functionalized polyethylene glycol resin via a thiol ether linkage and labeled with (99m)Tc-gluconate at room temperature, followed by elution of the HESA (99m)Tc-RP488 in saline (minimum specific activity approximately 1000 TBq/mmol by amino acid analysis). Both HESA and LESA (99m)Tc-RP488 labeled at > 90% purity. In vitro, HESA (99m)Tc-RP488 incubated with streptavidin-agarose was bound quantitatively, but there was competition from addition of increasing amounts of cold RP488. In rats, radiotracer uptake was evident at the site of implantation of streptavidin-agarose beads for the HESA dose, less uptake of low effective specific activity (LESA) material, and no appreciable uptake in the control rats of the LESA or HESA dose. The target-to-background ratio for HESA (99m)Tc-RP488 was 5.4 times that of the control. The solid-phase technology offers a convenient way to prepare high specific activity receptor-targeting (99m)Tc radiopharmaceuticals.