90Y and 177Lu Labeling of a DOTA-Conjugated Vitronectin Receptor Antagonist Useful for Tumor Therapy

Abstract

The ⁹⁰Y and ¹⁷⁷Lu 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 ⁹⁰Y 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 ⁹⁰Y by SU015 is slow, so that heating at elevated temperatures (50−100 °C) is needed to complete the ⁹⁰Y-labeling. The rate of ⁹⁰Y 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 °C for 5−10 min), the minimum amount of SU015 required to achieve 95% RCP for RP697 is ∼25 μg for 20 mCi of ⁹⁰YCl₃ corresponding to a SU015:⁹⁰Y ratio of ∼30:1.