107610-25-3

Upstream product

• 132151-79-2 C₉H₁₀⁽¹⁸⁾FNO₂ 
• 92812-82-3 [18F]-L-3,4-dihydroxy-6-fluorophenylalanine 

Relevant academic research and scientific papers

Improved, one-pot synthesis of 6-[18F]fluorodopamine and quality control testing for use in patients with neuroblastoma

6-[18F]Fluorodopamine ([18F]F-DA) is taken into cells via the norepinephrine transporter (NET). Recent [18F]F-DA positron emission tomography–computed tomography (PET-CT) imaging of adult neuroendocrine tumors shows a dramatic improvement in sensitivity over the standard-of-care, meta-iodobenzylguanidine (MIBG) single-photon emission computed tomography (SPECT)–CT. A new precursor (ALPdopamine) allows no-carrier-added synthesis resulting in high–molar activity [18F]F-DA. Automated synthesis of [18F]F-DA was performed in a single reactor using a two-step procedure: 1) fluorination via thermolysis of a diaryliodonium salt precursor, followed by 2) acid hydrolysis. Phase transfer agents, Kryptofix 222 and two tetraalkylammonium salts, were investigated. Optimized synthesis of [18F]F-DA was achieved in 56 to 60?minutes (26% end of synthesis [EOS], nondecay corrected). The product passed all Food and Drug Administration (FDA)–required quality control testing for human use. Accumulation of [18F]F-DA in SK-N-BE(2)-C (high NET expression) cells was significantly higher than in SH-EP (minimal NET expression) cells (P?18F]F-DA for human use. Validation of uptake by neuroblastoma (NB) cell lines supports the use of [18F]F-DA for imaging NB patients. A pediatric NB imaging trial using [18F]F-DA PET has been approved (Investigational New Drug application (IND) no. 138638) based on the methods reported here. We expect [18F]F-DA will be localized in NB tumors and that high-quality functional images will be obtained within minutes after injection.

Fast enzymatic synthesis of n.c.a. 6-[18F]fluorodopamine (FDA) from n.c.a. 6-[18F]FDOPA and the fate of 6-FDOPA and 6-FDA in neuroblastoma and Caki-1 cells after their uptake

The catecholamine analogue [123I]mIBG has been used for scintigraphic imaging of neuroblastoma since 1984. It is taken up by the noradrenaline transporter (NAT), which is present in most neuroblastoma cells. An alternative imaging method could

A Practical One-Pot Synthesis of Positron Emission Tomography (PET) Tracers via Nickel-Mediated Radiofluorination

Recently a novel method for the preparation of 18F-labeled arenes via oxidative [18F]fluorination of easily accessible and sufficiently stable nickel complexes with [18F]fluoride under exceptionally mild reaction conditions was published. The suitability of this procedure for the routine preparation of clinically relevant positron emission tomography (PET) tracers, 6-[18F]fluorodopamine (6-[18F]FDA), 6-[18F]fluoro-l-DOPA (6-[18F]FDOPA) and 6-[18F]fluoro-m-tyrosine (6-[18F]FMT), was evaluated. The originally published base-free method was inoperative. However, a "low base" protocol afforded protected radiolabeled intermediates in radiochemical conversions (RCCs) of 5-18 %. The subsequent deprotection step proceeded almost quantitatively (>95 %). The simple one-pot two-step procedure allowed the preparation of clinical doses of 6-[18F]FDA and 6-[18F]FDOPA within 50min (12 and 7 % radiochemical yield, respectively). In an unilateral rat model of Parkinsons disease, 6-[18F]FDOPA with high specific activity (175GBq μmol-1) prepared using the described nickel-mediated radiofluorination was compared to 6-[18F]FDOPA with low specific activity (30MBq μmol-1) produced via conventional electrophilic radiofluorination. Unexpectedly both tracer variants displayed very similar in vivo properties with respect to signal-to-noise ratio and brain distribution, and consequently, the quality of the obtained PET images was almost identical. Fast and simple: 6-[18F]FDOPA, 6-[18F]FMT, and 6-[18F]FDA were efficiently prepared via a one-pot two-step procedure using nickel-mediated radiofluorination under "low base" conditions. In a rat model of Parkinsons disease, the biodistribution and, consequently, the imaging property of 6-[18F]FDOPA were found to be independent of specific activity.

Synthesis of 6-[18F]fluorodopamine, 6-[18F]fluoro-m-tyramine and 4-[18F]fluoro-m-tyramine

h. new method for the preparation of 6-[18F]fluorodopamine (3) and [18F]fluorinated analogs of m-tyramine based on a regioselective radiofluorodestannylation reaction has been developed. The radiofluorodestannylation of 6-trimethylstannyldopamine derivative 1 was carried out with [18F]F2 to give the corresponding [18F]fluoro intermediate 2. Acid deprotection of 2 with 48% HBr followed by HPLC purification afforded 6-[18F]fluorodopamine (3) in 18% radiochemical yield. Similarly, 6- and 4-[18F]fluoro-m-tyramines and 6b) were prepared from their corresponding trimethylstannyl-m-tyramine derivatives in 25 and 8% radiochemical yields, respectively. In all cases, after HPLC purification of the final products, tin concentrations were found to be 15 ppb.

Copper-mediated aromatic radiofluorination revisited: Efficient production of PET tracers on a preparative scale

Two novel methods for copper-mediated aromatic nucleophilic radiofluorination were recently reported. Evaluation of these methods reveals that, although both are efficient in small-scale experiments, they are inoperative for the production of positron emission tomography (PET) tracers. Since high base content turned out to be responsible for low radiochemical conversions, a "low base" protocol has been developed which affords 18F-labeled arenes from diaryliodonium salts and aryl pinacol boronates in reasonable yields. Furthermore, implementation of our "minimalist" approach to the copper-mediated [18F]-fluorination of (mesityl)(aryl)iodonium salts allows the preparation of 18F-labeled arenes in excellent RCCs. The novel radiofluorination method circumvents time-consuming azeotropic drying and avoids the utilization of base and other additives, such as cryptands. Furthermore, this procedure enables the production of clinically relevant PET tracers; [18F]FDA, 4-[18F]FPhe, and [18F]DAA1106 are obtained in good isolated radiochemical yields. Additionally, [18F]DAA1106 has been evaluated in a rat stroke model and demonstrates excellent potential for visualization of translocator protein 18 kDa overexpression associated with neuroinflammation after ischemic stroke.

Efficient automated syntheses of high specific activity 6-[18F]fluorodopamine using a diaryliodonium salt precursor

6-[18F]Fluorodopamine (6-[18F]F-DA) is a positron emission tomography radiopharmaceutical used to image sympathetic cardiac innervation and neuroendocrine tumors. Imaging with 6-[18F]F-DA is constrained, in part, by the bi

ACETYLATED PRODRUGS FOR DELIVERY ACROSS THE BLOOD-BRAIN BARRIER

The present disclosure relates to pharmaceutical compositions including a compound derived from a parent compound having a hydroxyl or amino moiety, wherein the hydroxyl in the parent compound is presented as an ester in the compound or the amino in the parent compound is presented as an amide in the compound, and their use to prevent or treat neurological disease.

Alcohol-Enhanced Cu-Mediated Radiofluorination

The potential of many 18F-labeled (hetero)aromatics for applications in positron emission tomography remains underexplored because convenient procedures for their radiosynthesis are lacking. Consequently, simple methods to prepare radiofluorinated (hetero)arenes are highly sought after. Herein, we report the beneficial effect of primary and secondary alcohols on Cu-mediated 18F-labeling. This observation contradicts the assumption that such alcohols are inappropriate solvents for aromatic fluorination. Therefore, we developed a protocol for rapid radiolabeling of an extraordinarily broad scope of boronic and stannyl substrates under general reaction conditions. Notably, radiofluorinated indoles, phenols, and anilines were synthesized directly from the corresponding unprotected precursors. Furthermore, the novel method enabled the preparation of radiofluorinated tryptophans, [18F]F-DPA, [18F]DAA1106, 6-[18F]FDA, and 6-[18F]FDOPA.

Enhanced copper-mediated 18F-fluorination of aryl boronic esters provides eight radiotracers for PET applications

[18F]FMTEB, [18F]FPEB, [18F]flumazenil, [18F]DAA1106, [18F]MFBG, [18F]FDOPA, [18F]FMT and [18F]FDA are prepared from the corresponding arylboronic esters and [18