Convenient Preparation of No-Carrier-Added Technetium-99m Radiopharmaceuticals Using Solid-Phase Technology

• Published in: Bioconjugate chemistry 1999-09, Vol.10 (5), p.832-837
• Main Authors: Dunn-Dufault, Robert, Pollak, Alfred, Thornback, John R, Ballinger, James R
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Chelating Agents - chemistry; Chromatography, High Pressure Liquid; Isotope Labeling - methods; Ligands; Oligopeptides - chemistry; Organotechnetium Compounds - chemical synthesis; Organotechnetium Compounds - isolation & purification; Radiopharmaceuticals - chemical synthesis; Radiopharmaceuticals - isolation & purification; Reagent Kits, Diagnostic; Sodium Pertechnetate Tc 99m - chemistry
• ISSN: 1043-1802; 1520-4812
• DOI: 10.1021/bc990032f

A solid-phase technetium chelation chemistry was developed as a means of preparing 99mTc radiopharmaceuticals at high effective specific activity (HSA). Three peptidic N3S 99mTc ligands [mercaptoacetyl-Gly-Gly-Gly (MAG3), picolinyl-Ser-Cys-Gly-Thr-Lys-Pro-Pro-Arg (RP063), 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 99mTc chelators through a thiol ether linkage with Cys. The optimized loading of the supports ranged 6−122 μmol/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 [99mTc]pertechnetate (200−800 MBq) in the presence of stannous gluconate was achieved at room temperature for 30−60 min or in a 100 °C water bath for 10 min. Up to 80% of the activity was eluted from 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 99mTc products, demonstrating that extremely high effective specific activity can be achieved without the need for purification.