Stabilization of (90)y-labeled DOTA-biomolecule conjugates using gentisic acid and ascorbic acid.
Radiolytic degradation of radiolabeled compounds is a major challenge for the development of new therapeutic radiopharmaceuticals. The goal of this study is to explore the factors influencing the solution stability of a (90)Y-labeled DOTA-peptide conjugate (RP697), including the amount of total activity, the activity concentration, the stabilizer concentration, and the storage 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 100 mCi level under the same storage conditions. Radical scavengers, such as gentisic acid (GA) and ascorbic acid (AA), were used in combination with the low temperature (-78 degrees C) to prevent the radiolytic decomposition of RP697. It was found that RP697 remains stable for at least 2 half-lives of (90)Y when GA or AA (10 mg for 20 mCi of (90)Y) is used as a stabilizer when the radiopharmaceutical composition is stored at -78 degrees C. The stabilizer (GA and AA) can be added into the formulation either before or after radiolabeling. 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 other (90)Y-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-biomolecule conjugate toward radiolytic decomposition.
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Medical Imaging Division, DuPont Pharmaceuticals Company, 331 Treble Cove Road, North Billerica, Massachusetts 01862, USA. shuang.liu@dupontpharma.com
Edwards
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D001205:Ascorbic Acid / Q000737:chemistry*; D001288:Attention / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004355:Drug Stability; D016166:Free Radical Scavengers / Q000737:chemistry; D005841:Gentisates; D006573:Heterocyclic Compounds, 1-Ring / Q000138:chemical synthesis* / Q000737:chemistry*; D062385:Hydroxybenzoates / Q000737:chemistry*; D009842:Oligopeptides / Q000737:chemistry*; D010456:Peptides, Cyclic / Q000737:chemistry*; D012996:Solutions / Q000737:chemistry; D013696:Temperature; D015021:Yttrium Radioisotopes / Q000737:chemistry*
D016166:Free Radical Scavengers; D005841:Gentisates; D006573:Heterocyclic Compounds, 1-Ring; D062385:Hydroxybenzoates; D009842:Oligopeptides; D010456:Peptides, Cyclic; C436392:RP 697; D012996:Solutions; D015021:Yttrium Radioisotopes; C071349:1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid; D001205:Ascorbic Acid; C010925:2,5-dihydroxybenzoic acid