Automatic Synthesis of [18F]Altanserin, a Radiopharmaceutical for Positron Emission Tomographic Studies of the Serotonergic Type-2 Receptors

in Clinical Positron Imaging (1998), 1(2), 111-116

[18F]Altanserin is routinely used in several centers to study the serotonergic type-2 receptors (5HT2) with positron emission tomography (PET). An automatic production system allowing the preparation of ... [more ▼]

[18F]Altanserin is routinely used in several centers to study the serotonergic type-2 receptors (5HT2) with positron emission tomography (PET). An automatic production system allowing the preparation of multimillicurie amounts [>1.5 GBq (40 mCi) EOS, mean radiochemical yield 20 ± 6% EOB, specific activity >1 Ci/µmol Image] of this radiopharmaceutical within a synthesis time of 90 minutes (quality controls included) is described in this paper. The apparatus includes the recovery of the activity from the target, the preparation of the dried [18F]KF/kryptofix 2.2.2 complex, the labeling reaction using a microwave cavity, the Sep Pak and HPLC purification. A sterile, pyrogen-free and single use unit was also developed for the formulation of the injectable solution. This last part could be used for the formulation of many other radiopharmaceuticals. [less ▲]

No-carrier-added asymmetric synthesis of alpha-methyl-alpha-amino acids labelled with fluorine-18

in Tetrahedron (1997), 53(16), 5785-5796

Various [18F]fluoro aromatic α-methyl-L-amino acids 11 have been synthesized with high enantiomeric purity (ee > 97%). These new radiopharmaceuticals for Positron Emission Tomography (PET), potential ... [more ▼]

Various [18F]fluoro aromatic α-methyl-L-amino acids 11 have been synthesized with high enantiomeric purity (ee > 97%). These new radiopharmaceuticals for Positron Emission Tomography (PET), potential inhibitors of enzymatic functions, were regiospecifically labelled by nucleophilic substitution on trimethylammoniumbenzaldehyde triflate precursors 9. The [18F]fluoro aromatic aldehydes 12 obtained were easily converted to the corresponding [18F]fluorobenzyl halides [13 (X = 1)]. After alkylation of the lithium enolate of (2S,5S)-l-tert-Boc-2-tert-butyl-3,5-dimethyl-imidazolidin-4-one 2, the adducts were cleaved to give, after HPLC purification, various [18F]fluoro-α-methyl amino acid analogs with radiochemical yields of 10% (End of Bombardment, EOB) after a synthesis time of 120 min. The corresponding [19F]fluorinated amino acids 4 and [19F]fluoro intermediates were also prepared. [less ▲]

Enantioselective synthesis of 6-[fluorine-18]-fluoro-L-dopa from no-carrier-added fluorine-18-fluoride.

in Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine (1994), 35(12), 1996-2002

METHODS: A trimethylammonium veratraldehyde triflate was synthesized and used as a precursor for the asymmetric synthesis of 6-[18F]fluoro-L-dopa. RESULTS: Its nucleophilic fluorination with 18F-fluoride ... [more ▼]

METHODS: A trimethylammonium veratraldehyde triflate was synthesized and used as a precursor for the asymmetric synthesis of 6-[18F]fluoro-L-dopa. RESULTS: Its nucleophilic fluorination with 18F-fluoride produced by the 18O(p,n)18F nuclear reaction on enriched 18O-water led to the corresponding no-carrier-added [18F]fluoroveratraldehyde (45 +/- 5% EOB). Diiodosilane was used to prepare the corresponding [18F]fluorobenzyl iodide (36.5 +/- 5.3% EOB). Akylation of (S)-1-tert-boc-2-tert-butyl-3-methyl-4-imidazolidinone with this electrophilic agent, hydrolysis and purification by preparative high-pressure liquid chromatography made 6-[18F]fluoro-L-dopa ready for human injection, in a 23% +/- 6% decay-corrected radiochemical yield. The enantiomeric purity and the specific activity were above 96% and 1 Ci/mumole respectively. CONCLUSION: Through this procedure, starting from 250 mCi of 18F-fluoride, multimillicurie amounts (32 +/- 8.5 mCi) of no-carrier-added 6-[18F]fluoro-L-dopa are now available at the end of synthesis (90 min) with a good radiochemical purity (more than 98%). [less ▲]

SYNTHESIS OF F-18 SUBSTITUTED AROMATIC-ALDEHYDES AND BENZYL BROMIDES, NEW INTERMEDIATES FOR NCA [F-18] FLUORINATION

in Applied Radiation & Isotopes (1992), 43(4), 485-494

The synthesis of various [F-18]fluoroaromatic aldehydes using activated nitro precursors and aminopolyether supported nucleophilic substitution with F-18(-) is reported. These radiolabelled fluorinated ... [more ▼]

The synthesis of various [F-18]fluoroaromatic aldehydes using activated nitro precursors and aminopolyether supported nucleophilic substitution with F-18(-) is reported. These radiolabelled fluorinated aldehydes (radiochemical yields: 50-75%) are powerful key intermediates leading after treatment with NaBH4 and SOBr2 (SOCl2) to further active intermediates for example substituted [F-18]fluorobenzyl bromides (yields 30-50% EOB). These benzaldehydes and bromides are particularly useful for the preparation of new radiopharmaceuticals (e.g. fluorotroprapride, fluorodexetimide) either by reductive amination or by aromatic N-alkylation. The preparation of various amino acids in D, L (50:50) or enriched L form by asymmetric synthesis is also possible (e.g. L-6-[F-18]fluorodopa, L-4-[F-18]fluoro-m-tyrosine). It can be anticipated that the F-18-labelled fluoroaldehydes will find widespread application in radiopharmaceutical chemistry. [less ▲]

2- and 4-[18F]fluorotropapride, two specific D2 receptor ligands for positron emission tomography: N.C.A. syntheses and animal studies.

in International Journal of Radiation Applications and Instrumentation. Part A : Applied Radiation and Isotopes (1992), 43(10), 1265-74

Tropapride, (exo)-2,3-dimethoxy-N-[8-(phenylmethyl)-8- azabicyclo[3.2.1]oct-3-yl]benzamide hydrochloride, has been labeled with fluorine-18 at the 2- and 4-positions of its benzylic group. Two synthetic ... [more ▼]

Tropapride, (exo)-2,3-dimethoxy-N-[8-(phenylmethyl)-8- azabicyclo[3.2.1]oct-3-yl]benzamide hydrochloride, has been labeled with fluorine-18 at the 2- and 4-positions of its benzylic group. Two synthetic pathways were investigated: the first one required the alkylation of the norbenzyl precursor with 2- or 4-[18F]fluorobenzyl bromide (radiochemical yield of 5% EOB, 180 min); the second method consisted of a reductive amination of norbenzyl tropapride with 2- or 4-[18F]fluorobenzaldehyde (20% EOB, 110 min). In both cases, the specific activity was found to be greater than 1 Ci/mumol (EOS). Animal studies in rats showed the percentage of the injected dose localizing in the whole brain to be 0.6 +/- 0.09 and 0.2 +/- 0.03 at 2 h post injection for the para- and the ortho-[18F]fluoro analogs of tropapride respectively. Cerebral biodistribution studies showed at 4 h a striatum uptake of 5 +/- 0.7% of the injected dose per gram of striatum for the para derivative with a low fixation into the frontal cortex and the cerebellum (% ID/g FC < 0.4 and % ID/g Cb < 0.3). The selectivity of 4-[18F]fluorotropapride for D2 dopaminergic sites was demonstrated through blocking experiments with ketanserin, spiperone and halopemide. The saturability was confirmed by the use of variable specific activities. These preliminary results showed that 4-[18F]fluorotropapride can be considered as a potent radiopharmaceutical for the study of the dopaminergic system with PET. [less ▲]