A fully automated synthesis for the preparation of ⁶⁸Ga-labelled peptides

Background 

Generator-produced ⁶⁸Ga has attracted increasing interest for radiolabelling peptides used in PET applications. So far, the synthesis of ⁶⁸Ga-peptide radiopharmaceuticals is mainly based on semi-automated systems. Here we describe a fully automated approach for the synthesis of ⁶⁸Ga-labelled peptides.

Method 

A commercially available ⁶⁸Ga generator was eluted with 0.1 mol · l⁻¹ HCl. Reaction parameters such as buffer conditions, pH range, reaction temperature and time, volume of reaction solution and generator fraction were optimized for labelling DOTA-Tyr³-octreotide (DOTATOC). Reaction yields, pH, radiochemical purity, sterility, endotoxins, breakthrough of ⁶⁸Ge and final ⁶⁸Ge content were determined. A fully automated radiopharmaceutical synthesis device based on a modular concept for remote-controlled processing was developed and evaluated for a number of DOTA-derivatized peptides.

Results 

DOTATOC could be labelled in almost quantitative yields by heating 10–50 nmol peptide at pH 3.5–4.0 for 5 min at 95°C in 1.5 ml. Purification using a reversed-phase cartridge was required to avoid any potential ⁶⁸Ge breakthrough: final activities of ⁶⁸Ge were below 100 Bq · ml⁻¹. Automated synthesis resulted in overall decay-corrected reaction yields of about 60% within 10 min. Even after 1 year using a 1110 MBq generator more than 130 MBq ⁶⁸Ga-DOTATOC could be obtained. Moreover, it was demonstrated that a variety of DOTA-derivatized peptides can be labelled using identical reaction conditions with high yields.

Conclusion 

The system described allows the fully automated, efficient and rapid preparation of ⁶⁸Ga-DOTA-derivatized peptides. It has been used successfully and reliably for routine preparations in clinical studies.