In Vivo Biodistribution of No-Carrier-Added 6-F-18-Fluoro-3, 4-Dihydroxy-L-Phenylalanine (F-18-DOPA), Produced by a New Nucleophilic Substitution Approach, Compared with Carrier-Added F-18-DOPA, Prepared by Conventional Electrophilic Substitution

A novel synthetic approach to 6-F-18-fluoro-3,4-dihydroxy-L-phenylalanine (F-18-DOPA), involving the nucleophilic substitution of a diaryliodonium salt precursor with non-carrier-added F-18-fluoride, yielded a product with a specific activity that was 3 orders of magnitude higher than the product of the conventional synthesis method, involving an electrophilic substitution of a trialkylstannane precursor with F-18(2). We performed a direct comparison of high-and lowspecific-activity F-18-DOPA in a neuroendocrine tumor model to determine whether this difference in specific activity has implications for the biologic behavior and imaging properties of F-18-DOPA. Methods: F-18-DOPA was produced via the novel synthesis method, yielding F-18-DOPA-H with a high specific activity (35,050 +/- 4,000 GBq/mmol). This product was compared in several experiments with conventional F-18-DOPA-L with a low specific activity (11 +/- 2 GBq/mmol). In vitro accumulation experiments with the human pancreatic neuroendocrine tumor cell line BON-1 were performed at both 0 degrees C and 37 degrees C and at 37 degrees C in the presence of pharmacologic inhibitors of proteins involved in the uptake mechanism of F-18-DOPA. Small-animal PET experiments were performed in athymic nude mice bearing a BON-1 tumor xenograft. Results: At 37 degrees C, the uptake of both F-18-DOPA-H and F-18-DOPA-L did not differ significantly during a 60-min accumulation experiment in BON-1 cells. At 0 degrees C, the uptake of F-18-DOPA-L was significantly decreased, whereas the lower temperature did not alter the uptake of F-18-DOPA-H. The pharmacologic inhibitors carbidopa and tetrabenazine also revealed differential effects between the 2 types of F-18-DOPA in the 60-min accumulation experiment. The small-animal PET experiments did not show any significant differences in distribution and metabolism of F-18-DOPA-H and F-18-DOPA-L in carbidopapretreated mice. Conclusion: The advantages of the novel synthesis of F-18-DOPA, which relies on nucleophilic fluorination of a diaryliodonium salt precursor, lie in the simplicity of the synthesis method, compared with the conventional, electrophilic approach and in the reduced mass of administered, pharmacologically active F-19-DOPA. F-18-DOPA-H demonstrated comparable imaging properties in an in vivo model for neuroendocrine tumors, despite the fact that the injected mass of material was 3 orders of magnitude less than F-18-DOPA-L.