Use of 65Zn as a tracer for the assessment of purification in the 68Ga-DOTANOC synthesis

•We studied 68Ga-DOTANOC radionuclidic purity and 68Zn distribution in the synthesis.•68Zn behavior was inspected by using cyclotron produced 65Zn as a radiotracer.•68Zn competes with 68Ga in labeling DOTANOC with a (95±2)% labeling yield.•Effectiveness of the STRATA X-C cationic cartridge in lowering the amount of 68Zn to less than 1%.•68Ga-DOTANOC radionuclidic purity was (99.9999986±0.0000006)%, superior to required 99.9%.

In the last years 68Ga has got into the focus of researchers and clinicians especially for radio-labeling of biomolecules; an important characteristic of this positron emitting isotope is its availability via the 68Ge/68Ga generator system: the long-lived 68Ge (t1/2=270.8 d) produces the short-lived 68Ga (t1/2=67.63 min) which decays to stable 68Zn. 68Ge breakthrough compromises 68Ga radionuclidic purity, while 68Zn might affect the specific activity of the radiopharmaceutical. In this paper we investigated the weight of these impurities in 68Ga-DOTANOC synthesis.65Zn (t1/2=244.26 d; decay mode: EC 98.3%, β+ 1.7%) was used as a radiotracer of stable 68Zn; samples of the purification columns, wastes and product were recovered and measured with a calibrated HPGe gamma-ray spectrometry system.The results showed that 68Zn competes with 68Ga in labeling DOTANOC with a (95±2)% labeling yield; they also proved the effectiveness of the STRATA X-C cationic post-processing of the generator eluate in lowering the amount of this impurity to less than 1%. Moreover this approach, along with the purification of the final product through a STRATA X cartridge, effectively removes 68Ge breakthrough providing a 68Ga-DOTANOC radionuclidic purity of (99.9999986±0.0000006)%, superior to 99.9% required by the Pharmacopoeia Monograph on 68Ga Edotreotide injection.