Ascorbic Acid:  Useful as a Buffer Agent and Radiolytic Stabilizer for Metalloradiopharmaceuticals

• Published in: Bioconjugate chemistry Vol. 14; no. 5; pp. 1052 - 1056
• Main Authors: Liu, Shuang, Ellars, Charlie E, Edwards, D. Scott
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 01.09.2003
• Subjects: Ascorbic Acid - chemistry; Ascorbic Acid - metabolism; Buffers; Heterocyclic Compounds - chemistry; Heterocyclic Compounds - metabolism; Organometallic Compounds - chemistry; Organometallic Compounds - metabolism; Radiopharmaceuticals - chemistry; Radiopharmaceuticals - metabolism
• ISSN: 1043-1802; 1520-4812
• DOI: 10.1021/bc034109i

The goal of this study is to explore the use of ascorbic acid (AA) as a buffer agent and a radiolytic stabilizer for preparation and stabilization of radiolabeled DOTA−biomolecule conjugates. Results from a titration experiment show that 0.1 M AA solution has sufficient buffer capacity at pH 5.0 while 0.5 M AA solution is useful even at pH 6.0. The radiolabeling experiment using TA138, a DOTA-conjugated nonpeptide integrin αvβ3 receptor antagonist, clearly demonstrates that AA is a good buffer agent for pH control and an excellent antioxidant for stabilization of metal-labeled diagnostic (111In) and therapeutic (90Y and 177Lu) radiopharmaceuticals if the radiolabeling is performed at pH 5−6. There is no need for the additional stabilizer (e.g., gentisic acid) and buffer agent such as ammonium acetate. The anaerobic AA formulation described in this study is particularly useful for radiolabeling of small biomolecules, which are sensitive to the radiolytic degradation during radiolabeling.