An improved assay for 68Ga-hydroxide in 68Ga-DOTATATE formulations intended for neuroendocrine tumour imaging

The objective of this study was to identify a more rapid assay for Ga-68(OH)(3) impurity in Ga-68-DOTATATE formulations. Three methods were used to prepare Ga-68(OH)(3) reference material (pharmacopoeial, bench titration and automated radiosynthesis), and four quality control methods for its assessment (thin layer chromatography, membrane filtration, HPLC and solid phase extraction). The optimal method of preparing Ga-68(OH)(3) was by titrating Ga-68(3+) with buffered sodium hydroxide solutions to pH 5.6 +/- 0.2. The precipitate was quantitatively isolated by membrane filtration (0.02 mu m)/hydrochloric acid (HCl; pH 5.6) solvent, and also it remained 100% at the origin on instant thin layer chromatography with silica gel paper/HCl (pH 5.6) solvent. For Ga-68-DOTATATE samples, the thin layer chromatography technique was used with a single paper strip developed separately on two occasions, once in HCl (pH 5.6) and next in methanol solvent. This so-called double-developed (DD) method separated Ga-68(OH)(3) impurity located at the origin, from Ga-68-DOTATATE plus Ga-68(3+) at similar to R-f 0.4, and it was superior to the other methods. It assayed for the impurity similarly to the pharmacopoeial method. The advantages of the DD method were that it required inexpensive test materials and it reproducibly determined % Ga-68(OH)(3) in Ga-68-DOTATATE in 12min, 13min earlier than the pharmacopoeial method. This time efficiency resulted in a surplus of 12% Ga-68-DOTATATE counts in the product vial, and this provided a contingency of radioactivity or time for the injection/imaging processes in the Nuclear Medicine Department.