Convenient preparation of no-carrier-added technetium-99m radiopharmaceuticals using solid-phase technology

A solid-phase technetium chelation chemistry was developed as a means of preparing Tc-99m radiopharmaceuticals at high effective specific activity (HSA). Three peptidic N3S Tc-99m ligands [mercaptoacetyl-Gly-Gly-Gly (MAG3), picolinyl-Ser-Cys-Gly-Thr-Lys-Pro-Pro-Arg (RPO63), and dimethyl-Gly-Ser-Cys-Gly-Thr-Lys-Pro-Pro-Arg (RP128)] were used. The free thiol of Cys in each was attached to a series of commercially available amine-functionalized supports in a two-step process. The amine groups on the solid supports were converted to maleimide groups followed by the attachment of the Tc-99m chelators through a thiol ether linkage with Cys. The optimized loading of the supports ranged 6-122 mu mol/g support as determined by amino acid analysis. Each of the peptide-loaded supports (50-100 mg) was placed in either glass syringe vessels or disposable chromatography columns. Labeling with [Tc-99m]pertechnetate (200-800 MBq) in the presence of stannous gluconate was achieved at room temperature for 30-60 min or in a 100 degrees C water bath for 10 min. Up to 80% of the activity was eluted fi om the column with saline to give products with purity up to 99.8% as determined by HPLC. Amino acid analysis indicated as little as 100 pmol of peptide present in the Tc-99m products, demonstrating that extremely high effective specific activity can be achieved without the need for purification.