RT Journal Article
SR Electronic
T1 In Vivo Biodistribution of No-Carrier-Added 6-<sup>18</sup>F-Fluoro-3,4-Dihydroxy-<span class="sc">l</span>-Phenylalanine (<sup>18</sup>F-DOPA), Produced by a New Nucleophilic Substitution Approach, Compared with Carrier-Added <sup>18</sup>F-DOPA, Prepared by Conventional Electrophilic Substitution
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 106
OP 112
DO 10.2967/jnumed.114.145730
VO 56
IS 1
A1 Kuik, Willem-Jan
A1 Kema, Ido P.
A1 Brouwers, Adrienne H.
A1 Zijlma, Rolf
A1 Neumann, Kiel D.
A1 Dierckx, Rudi A.J.O.
A1 DiMagno, Stephen G.
A1 Elsinga, Philip H.
YR 2015
UL http://jnm.snmjournals.org/content/56/1/106.abstract
AB A novel synthetic approach to 6-18F-fluoro-3,4-dihydroxy-l-phenylalanine (18F-DOPA), involving the nucleophilic substitution of a diaryliodonium salt precursor with non-carrier-added 18F-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 18F2. We performed a direct comparison of high- and low-specific-activity 18F-DOPA in a neuroendocrine tumor model to determine whether this difference in specific activity has implications for the biologic behavior and imaging properties of 18F-DOPA. Methods: 18F-DOPA was produced via the novel synthesis method, yielding 18F-DOPA-H with a high specific activity (35,050 ± 4,000 GBq/mmol). This product was compared in several experiments with conventional 18F-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°C and 37°C and at 37°C in the presence of pharmacologic inhibitors of proteins involved in the uptake mechanism of 18F-DOPA. Small-animal PET experiments were performed in athymic nude mice bearing a BON-1 tumor xenograft. Results: At 37°C, the uptake of both 18F-DOPA-H and 18F-DOPA-L did not differ significantly during a 60-min accumulation experiment in BON-1 cells. At 0°C, the uptake of 18F-DOPA-L was significantly decreased, whereas the lower temperature did not alter the uptake of 18F-DOPA-H. The pharmacologic inhibitors carbidopa and tetrabenazine also revealed differential effects between the 2 types of 18F-DOPA in the 60-min accumulation experiment. The small-animal PET experiments did not show any significant differences in distribution and metabolism of 18F-DOPA-H and 18F-DOPA-L in carbidopa-pretreated mice. Conclusion: The advantages of the novel synthesis of 18F-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 19F-DOPA. 18F-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 18F-DOPA-L.