6-[18F]fluoro-l-dihydroxyphenylalanine (18F–DOPA) is a diagnostic positron emission tomography (PET) agent, which has been used for decades in imaging the loss of dopaminergic neurons in Parkinson's disease, and more recently to detect, stage and restage neuroendocrine tumors (NETs) and to search for recurrence of viable glioma tissue. The commercially available 18F–DOPA PET radiopharmaceutical for diagnostic use in European Union countries, is formulated in an aqueous solution of acetic acid (1.05 mg/mL) and has the disadvantages that, immediately before injection, the pH must be adjusted to 4.0–5.0 by the addition of a sterile solution of sodium bicarbonate (84 mg/mL) causing a light and transient burning sensation at the injection site. To overcome these drawbacks, preformulation studies were accomplished to confirm that F-DOPA degradation was affected by pH. Hence, two formulations of F-DOPA, namely ND1 and ND2, were prepared maintaining the pH = 5.0 using 1 mM l-(+)-lactate buffer, excluding oxygen, and incorporating in the formula the chelating agent Na2EDTA (1 mM). F-DOPA oxygen exposure, the presence of free metal cations in formulation and high pH values seem to promote F-DOPA degradation. The resulting formulations proved to guarantee the chemical stability of F-DOPA in solution at pH 5.0, value also compatible with the direct infusion. In vitro cell viability tests on mouse skeletal muscle fibers, renal tsa201 and neuronal SH-SY5Y cell lines, and in vivo studies in rats reported elsewhere, showed cell tolerability to the new F-DOPA formulations providing the basis for their further in vivo evaluation.