Preparation Method, Quality Control, and Stability Studies of the Radiopharmaceutical Gallium [68Ga]Ga-edotreotide

ABSTRACT
Purpose: Gallium-68-based radiopharmaceuticals are widely employed in Nuclear Medicine for
PET/CT imaging, particularly in the diagnosis, staging, and monitoring of neuroendocrine tumors
(NETs). This study focuses on the evaluation of the radiochemical and chemical purity of Gallium
[68Ga]Ga-edotreotide, also known as [68Ga]Ga-DOTA-TOC, to determine its valid shelf-life
following the end of synthesis (EOS).
Methods: The stability study was carried out in accordance with Chapter 10 of the Good
Preparation Guidelines for Radiopharmaceuticals, under both standard and "worst-case"
conditions. All analytical methods complied with the specifications of the European Pharmacopoeia
Monograph 01/2022:2482 (Ph. Eur.), Gallium (68Ga) edotreotide injection.
Results: Under standard conditions, [68Ga]Ga-edotreotide maintained a radiochemical purity
above the threshold specified by the European Pharmacopoeia (≥ 95%) up to 3 hours post-EOS.
At 4 hours, purity dropped below the specification limits. The assessment of chemical purity
confirmed these findings, with impurities exceeding limits at the 4-hour mark. Under "worst-case"
storage conditions, a similar stability pattern was observed for samples stored in plastic syringes
and those subjected to mild heating (30°C and 40°C). However, for samples stored under
refrigerated conditions at 4°C, radiochemical purity dropped below the acceptable limit as early as
3 hours after synthesis.
Conclusion: The radiopharmaceutical [68Ga]Ga-edotreotide prepared using an automated
synthesis module is stable for up to 3 hours after synthesis. No significant differences in stability
are observed between storage in glass vials and plastic syringes. While exposure to mild heating
up to 40°C does not alter the product quality, refrigeration at 4°C prematurely compromises the
complex structure and radiochemical purity.

Keywords: Radiopharmaceuticals, [68Ga]Ga-edotreotide, Synthesis, Quality Control,
Stability Study, Neuroendocrine Tumors, HPLC.