Customized synthesis of Ga-68 DOTATATE

Objectives Ga-68 labeled somatostatin peptide has high clinical significance. We altered the synthesis protocol, the amount of peptide used & also discussed associated problems.

Methods Peptide (10-25μg) was transferred slowly to preheated reactor. The Ga-68 was eluted into the reactor. Solution was heated for 10 min & slowly transferred to the waste vial after passing through preconditioned C-18 cartridge. The labeled peptide from C-18 cartridge was eluted slowly with ethanol and passed through 0.22μ filter to a product vial. Activity, pH of waste & product was checked every time. When generator (25 mCi) was new, we used 25μg peptide. When the yield of generator was ~50%, the amount of peptide was reduced to 10-15 μg. The patients were uncomfortable during injection. The pH of labeled peptide was ~5. We tried- a) passed 1ml 0.1M acetate buffer in the product vial through 0.22 μm filter, b) after elution of peptide from the C-18 cartridge with 30% ethanol, 5ml saline was passed followed by 1 ml 0.1M acetate buffer & 4 ml saline. The connecting tubes, connectors, reactor & valves were changed after 10 synthesis.

Results Good labeling yield was obtained after elimination of peptide heating & with 15 μg peptide after ~50% elution yield of generator. The yield was drastically decreased when 10 μg peptide was used. So, the optimum peptide for synthesis is 15μg. pH of product was ~5, addition of buffer in either way gave relief to the patient during injection. The labeling yield was considerably low when pH of waste was >4 or >5. The reason was, at pH <4, Ga-68 did not chelate with DOTA and above 5, Ga-68 formed hydroxide & was not available for chelating. It should be noted that generator should be connected with one way valve to synthesis module otherwise labeled peptide may be pushed to the generator. Better results are obtained with slow loading & transfer of solution and elution from cartridge.

Conclusions Reduction of peptide amount is not only cost effective but may reduce the competitive binding of unlabeled peptide to receptors. Discussed problems may be helpful to patients & radiochemists.