90Y and 177LU labeling of a DOTA-conjugated vitronectin receptor antagonist useful for tumor therapy

The Y-90 and Lu-177 complexes (RP697 and RP688, respectively) of a DOTA-conjugated vitronectin receptor antagonist (SU015: 2-(1,4,7, 10-tetraaza-4,7, 10-tris(carboxymethyl)-1-cyclododecyl)acetyl-Glu-(cyclo{ Lys-Arg-Gly-Asp-D-Phe})(cyclo{Lys-Arg-Gly-Asp-D-Phe})were prepared by reacting SU015 with the radiometal chloride in ammonium acetate buffer (pH > 7.2) in the presence of an antioxidant (sodium gentisate, GA). Through a series of radiolabeling experiments, it was found that there are many factors influencing the rate of Y-90 chelation and the radiolabeling efficiency of SU015. These include the purity of SU015, the pH, reaction temperature, and heating time, as well as the presence of trace metal contaminants, such as Ca2+, Fe3+, and Zn2+. The chelation of Y-90 by SU015 is slow, so that heating at elevated temperatures (50-100 degreesC) is needed to complete the Y-90-labeling. The rate of Y-90 chelation is also dependent on the pH of the reaction mixture. Under optimized radiolabeling conditions (pH 7.2-7.8 and heating at 50-100 degreesC for 5-10 min), the minimum amount of SU015 required to achieve 95% RCP for RP697 is similar to 25 mug for 20 mCi of (YCl3)-Y-90 corresponding to a SU015:Y-90 ratio of similar to 30:1.