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


METHODS
A commercially available Ga generator was eluted with 0.1 mol . l 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-Tyr-octreotide (DOTATOC). Reaction yields, pH, radiochemical purity, sterility, endotoxins, breakthrough of Ge and final Ge 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 degrees C in 1.5 ml. Purification using a reversed-phase cartridge was required to avoid any potential Ge breakthrough: final activities of Ge were below 100 Bq . ml. 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 Ga-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.


CONCLUSIONS
The system described allows the fully automated, efficient and rapid preparation of Ga-DOTA-derivatized peptides. It has been used successfully and reliably for routine preparations in clinical studies.
Decristoforo
Clemens
C
Clinical Department of Nuclear Medicine, Medical University Innsbruck, Austria. Clemens.Decristoforo@uki.at
Knopp
Roger
R
von Guggenberg
Elisabeth
E
Rupprich
Marco
M
Dreger
Thorsten
T
Hess
Andre
A
Virgolini
Irene
I
Haubner
Roland
R
D001331:Automation; D002851:Chromatography, High Pressure Liquid; D002855:Chromatography, Thin Layer; D005708:Gallium / Q000737:chemistry*; D005857:Germanium / Q000737:chemistry; D007202:Indicators and Reagents; D007553:Isotope Labeling / Q000379:methods; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000737:chemistry; D010455:Peptides / Q000138:chemical synthesis*; D011868:Radioisotopes / Q000737:chemistry; D019275:Radiopharmaceuticals / Q000138:chemical synthesis*; D015203:Reproducibility of Results; D013242:Sterilization
D007202:Indicators and Reagents; D009942:Organometallic Compounds; D010455:Peptides; D011868:Radioisotopes; D019275:Radiopharmaceuticals; D005857:Germanium; C513399:gallium Ga 68 dotatate; D005708:Gallium