Introduction. The development of universal dry kit which would contain the active ingredient and excipients allowing efficient ⁶⁸Ga radiolabeling regardless the HCl concentration of ⁶⁸Ge/⁶⁸Ga generator eluate remains a challenge. Our aim was to develop a dry kit formulation for ⁶⁸Ga radiolabeling of the PSMA inhibitor, PSMA-11 (Glu-CO-Lys(Ahx)-HBED-CC).

Methods. A series of “wet” experiments using various amounts of sodium acetate and ascorbic acid were performed to maintain pH between 4 and 5 when adding increasing volumes of ⁶⁸Ga eluate (1 - 4mL 0.1M HCl). Radiochemical purity RCP was assessed by RP-RadioHPLC (Kinetex C18 150mm; A: 0.1%TFA/H2O, B: 0.1%TFA/CAN) gradient (1) and isocratic elution (optimally set to 17% B) to assess ⁶⁸Ga-PSMA-11 and non-labelled PSMA-11(UV detection). RCP also was tested using ITLC SG  in 3 different solvents (1) 0.9%NaCl/MeOH 80/20 v/v; (2) 0.9%NaCl/MeOH/25%NH₃, 80/20/5 v/v/v; (3) 1M NH₄OAc/MeOH 50/50 v/v.

Results and discussion. Ascorbic acid (25mg/mL) increased RCP to 98.8% compared to acetate buffer only (around 95.0%). The dry kit formulation containing 30 µg of PSMA-11, 60 mg sodium acetate and 12,5 mg ascorbic acid yielded > 95% of ⁶⁸Ga-PSMA-11. When administered i.v. in healthy Balb/c mice (n=5) in 0.1mL (38 MBq/mL) (at 15, 30, 60 and 120min) ⁶⁸Ga-PSMA-11 rapidly cleared from the blood via kidney route with >70% urine elimination at 1h p.i. Biodistribution of free ⁶⁸Ga (buffered by sodium acetate or sodium acetate/ascorbic acid mixture) was also investigated. It is worth noting that presence of ascorbic acid favored blood clearance of free ⁶⁸Ga, probably due to the formation of week Ga complex with ascorbic acid and thus resulting in lower liver and spleen accumulation.