Endocrine Abstracts

Determination of radiochemical purity (RCP) of radiopharmaceuticals based on ⁶⁸Ga-BCA-peptides (⁶⁸Ga-DOTA-TOC/-TATE, ⁶⁸Ga-NODAGA-RGD₂, ⁶⁸Ga-PSMA-HBED-CC, etc.) is an extremely important part of QC in routine clinical practice. Nature of gallium leads to formation of two major radiochemical impurities in the radiopharmaceutical: hydrolyzed ⁶⁸Ga (colloid) and unbounded ionic forms of ⁶⁸Ga. The amounts of each impurity and ⁶⁸Ga-BCA-peptide are strictly normalized in accordance with pharmacopoeial standards. In 8th EuPh there is no method allowing to separate all of radiochemical impurities in ⁶⁸Ga preparations. Normally it takes to use combination of two systems to separate them (iTLC-SG and 1M ammonium acetate/methanol 50:50 (V/V) and HPLC or iTLC-SG–citric buffer).

In the present study, effective iTLC method for the determination of RCP of ⁶⁸Ga-radiopharmaceuticals was developed (with no double-developing, changing of eluents or additional manipulation). In this method iTLC-SG strips and commonly used eluent TFA_aq. (3–5% (V/V)) are used. The method allows determining each of the key radiochemical forms of ⁶⁸Ga (colloid, bound, free ionic) separately with the peaks separation being no less than 7–8 σ. Rf =0.0–0.1 for ⁶⁸Ga-colloid; Rf=0.5–0.6 for ⁶⁸Ga-BCA-peptides; Rf =0.9–1.0 for ionic ⁶⁸Ga:

The method is simple and fast: for developing of 100 mm strip only 4–6 min is required (versus 18–20 min for pharmacopoeial method). The combination of typical chromatographic systems mentioned above as well as gel-electrophoresis and SPE were used as control.

The method has been tested on various compounds (including ⁶⁸Ga-DOTA-TOC/-TATE, ⁶⁸Ga-NODAGA-RGD₂, etc.) and mixtures with different values of RCP. It was found, that content of ⁶⁸Ga-colloid and ionic ⁶⁸Ga(III) determined with the method developed correlates with control results very well. It also was found, that in some cases HPLC shows wrong RCP values (erroneously high) not only due to presence of ⁶⁸Ga-colloid, but due to presence of other ⁶⁸Ga-ionic species as well.