Stabilization of Y-90-labeled DOTA-biomolecule conjugates using gentisic acid and ascorbic acid

Radiolytic degradation of radiolabeled compounds is a major challenge for t he development of new therapeutic radiopharmaceuticals. The goal of this st udy is to explore the factors influencing the solution stability of a Y-90- labeled DOTA-peptide conjugate (RP697), including the amount of total activ ity, the activity concentration, the stabilizer concentration, and the stor age temperature. In general, the rate of radiolytic decomposition of RP697 is much slower at the lower activity concentration (<4 mCi/mL) than that at the higher concentration(> 10 mCi/mL). RP697 remains relatively stable at the 20 mCi level and room temperature while it decomposes rapidly at the 10 0 mCi level under the same storage conditions. Radical scavengers, such as gentisic acid (GA) and ascorbic acid (AA), were used in combination with th e low temperature (-78 degreesC) to prevent the radiolytic decomposition of RP697. It was found that RP697 remains stable for at least 2 half-lives of Y-90 when GA or AA (10 mg for 20 mCi of 90Y) is used as a stabilizer when the radiopharmaceutical composition is stored at -78 degreesC. The stabiliz er (GA and AA) can be added into the formulation either before or after rad iolabeling. The post-labeling approach is particularly useful when the use of a large amount of the stabilizer interferes with the radiolabeling. The radiopharmaceutical composition developed in this study can also apply to o ther Y-90-labeled DOTA-biomolecule conjugates. The amount of the stabilizer used in the radiopharmaceutical composition and storage temperature should be adjusted according to the sensitivity of the radiolabeled DOTA-biomolec ule conjugate toward radiolytic decomposition.