178433-03-9

Upstream product

• 60-18-4 L-tyrosine 
• 113426-12-3 [(18)F]-2-fluoroethyltosylate 
• 85725-77-5 1-bromo-2-[¹⁸F]fluoroethane 
• 849358-41-4 [¹⁸F]-(S)-(+)-2-tert-butoxycarbonylamino-3-[4-(2-fluoroethoxy)phenyl]propionic acid tert-butyl ester 
• 855698-96-3 t-Boc-(O-[18F]fluoroethyl)-L-Tyr-OBzl 

Relevant academic research and scientific papers

Fast and reliable generation of [18F]triflyl fluoride, a gaseous [18F]fluoride source

A novel strategy for the production of reactive [18F]fluoride has been developed, omitting time consuming azeotropic drying procedures. Gaseous [18F]triflyl fluoride is formed instantaneously at room temperature from hydrated [18F]fluoride, followed by distillation in less than 5 minutes into a dry aprotic solvent, in which dry [18F]fluoride is released in presence of base with >90% radiochemical yield. The reactivity of the [18F]fluoride has been confirmed by reaction with several model compounds and by the synthesis of the PET tracers [18F]fluoroestradiol ([18F]FES) and O-2-[18F]fluoroethyl-l-tyrosine ([18F]FET), providing good isolated radiochemical yields and molar activities of up to 123 GBq μmol?1.

Microfluidic technology: An economical and versatile approach for the synthesis of O-(2-[18F]fluoroethyl)-l-tyrosine ([18F]FET)

A new synthesis of O-(2-[18F]fluoroethyl)-l-tyrosine [ 18F]FET was developed using a NanoTek microfluidic synthesis system (Advion BioSciences, Inc.). Optimal reaction conditions were studied through screening different reaction parameters like temperature, flow rate, reaction time, concentration of the labeling precursor, and the applied volume ratio between the labeling precursor and [18F]fluoride. [ 18F]FET was obtained after HPLC purification with 50% decay-corrected radiochemical yield starting from as little as 40 μg of labeling precursor. Small animal PET studies in EMT-6 tumor bearing mice showed radioactivity accumulation in the tumor (SUV60min 1.21 ± 0.2) resulting in an slightly increasing tumor-to-muscle ratio over time.

Effect of α-Methyl versus α-Hydrogen Substitution on Brain Availability and Tumor Imaging Properties of Heptanoic [F-18]Fluoroalkyl Amino Acids for Positron Emission Tomography (PET)

Two [18F]fluoroalkyl substituted amino acids differing only by the presence or absence of a methyl group on the α-carbon, (S)-2-amino-7-[18F]fluoro-2-methylheptanoic acid ((S)-[18F]FAMHep, (S)-[18F]14) and (S)-2-amino-7-[18F]fluoroheptanoic acid ((S)-[18F]FAHep, (S)-[18F]15), were developed for brain tumor imaging and compared to the well-established system L amino acid tracer, O-(2-[18F]fluoroethyl)-l-tyrosine ([18F]FET), in the delayed brain tumor (DBT) mouse model of high-grade glioma. Cell uptake, biodistribution, and PET/CT imaging studies showed differences in amino acid transport of these tracer by DBT cells. Recognition of (S)-[18F]15 but not (S)-[18F]14 by system L amino acid transporters led to approximately 8-10-fold higher uptake of the α-hydrogen substituted analogue (S)-[18F]15 in normal brain. (S)-[18F]15 had imaging properties similar to those of (S)-[18F]FET in the DBT tumor model while (S)-[18F]14 afforded higher tumor to brain ratios due to much lower uptake by normal brain. These results have important implications for the future development of α-alkyl and α,α-dialkyl substituted amino acids for brain tumor imaging.

No carrier added synthesis of O-(2′-[18F]fluoroethyl)-l-tyrosine via a novel type of chiral enantiomerically pure precursor, NiII complex of a (S)-tyrosine Schiff base

O-(2′-[18F]fluoroethyl)-l-tyrosine ([18F]FET) has gained much attention as a promising amino acid radiotracer for tumor imaging with positron emission tomography (PET) due to favorable imaging characteristics and relatively long half-life of 18F (110 min) allowing remote-site application. Here we present a novel type of chiral enantiomerically pure labeling precursor for [18F]FET, based on NiII complex of a Schiff's base of (S)-[N-2-(N′-benzylprolyl)amino]benzophenone (BPB) with alkylated (S)-tyrosine, Ni-(S)-BPB-(S)-Tyr-OCH2CH2X (X = OTs (3a), OMs (3b) and OTf (3c)). A series of compounds 3a-c was synthesized in three steps from commercially available reagents. Non-radioactive FET as a reference was prepared from 3a in a form of (S)-isomer and (R,S) racemic mixture. Radiosynthesis comprised two steps: (1) n.c.a. nucleophilic fluorination of 3a-c (4.5-5.0 mg) in the presence of either Kryptofix 2.2.2.or tetrabutylammonium carbonate (TBAC) in MeCN at 80 °C for 5 min, followed by (2) removal of protective groups by treating with 0.5 M HCl (120 °C, 5 min). The major advantages of this procedure are retention of enantiomeric purity during the 18F-introduction step and easy simultaneous deprotection of amino and carboxy moieties in 3a-c. Radiochemically pure [18F]FET was isolated by semi-preparative HPLC (C18 μ-Bondapak, Waters) eluent aq 0.01 M CH3COONH4, pH 4/C2H5OH 90/10 (v/v). Overall synthesis time operated by Anatech RB 86 laboratory robot was 55 min. In a series of compounds 3a-c, tosyl derivative 3a provided highest radiochemical yield (40-45%, corrected for radioactive decay). Enantiomeric purity was 94-95% and 96-97%, correspondingly, for Kryptofix and TBAC assisted fluorinations. The suggested procedure involved minimal number of synthesis steps and suits perfectly for automation in the modern synthesis modules for PET radiopharmaceuticals. Preliminary biodistribution study in experimental model of turpentine-induced aseptic abscess and Glioma35 rat's tumor (homografts) in Wistar rats has demonstrated the enhanced uptake of radiotracer in the tumor area with minimal accumulation in the inflamed tissues.

A resin-linker-vector approach to radiopharmaceuticals containing 18F: Application in the synthesis of O-(2-[18F]- Fluoroethyl)-L-tyrosine

A Resin-linker-vector (RLV) strategy is described for the radiosynthesis of tracer molecules containing the radionuclide 18F, which releases the labelled vector into solution upon nucleophilic substitution of a polystyrene-bound arylsulfonate linker with [18F]-fluoride ion. Three model linker-vector molecules 7 a-c containing different alkyl spacer groups were assembled in solution from (4-chlorosulfonylphenyl)alkanoate esters, exploiting a lipase-catalysed chemoselective carboxylic ester hydrolysis in the presence of the sulfonate ester as a key step. The linker-vector systems were attached to aminomethyl polystyrene resin through amide bond formation to give RLVs 8 a-c with acetate, butyrate and hexanoate spacers, which were characterised by using magic-angle spinning (MAS) NMR spectroscopy. On fluoridolysis, the RLVs 8 a, b containing the longer spacers were shown to be more effective in the release of the fluorinated model vector (4-fluorobutyl)phenylcarbamic acid tert-butyl ester (9) in NMR kinetic studies and gave superior radiochemical yields (RCY≈60 %) of the 18F- labelled vector. The approach was applied to the synthesis of the radiopharmaceutical O-(2-[18F]-fluoroethyl)-L-tyrosine ([ 18F]-FET), delivering protected [18F]-FET in >90 % RCY. Acid deprotection gave [18F]-FET in an overall RCY of 41 % from the RLV. Copyright

New approach for the synthesis of [18F]fluoroethyltyrosine for cancer imaging: Simple, fast, and high yielding automated synthesis

O-(2-[18F]fluoroethyl)-L-tyrosine ([18F]FET) is one of the first 18F-labeled amino acids for imaging amino acid metabolism in tumors. This tracer overcomes the disadvantages of [ 18F]fluorodeoxyglucose, [18

18F-labeled tyrosine derivatives: Synthesis and experimental studies on accumulation in tumors and abscesses

Tyrosine derivatives labeled with a short-lived fluorine-18 isotope (T 1/2 110 min), namely 2-[18F]fluoro-L-tyrosine (FTYR) and O-(2′-[18F]fluoroethyl)-L-tyrosine (FET), promising radiopharmaceuticals (RPs) for positron em

A convenient method for the preparation of no-carrier-added O-(2-[18F]fluoroethyl)-L-Tyrosine)

This is a novel method for production of no-carrier-added O-(2-[18F]fluoroethyl)-L-Tyrosine which has been proved a suitable PET (position emission tomography) probe for tumor diagnosis imaging. The preparation of the title compound starts from precursors with the chemical structures as in Formula 1, wherein R1 is a protective group for the carboxyl functional group, R2 is a protective group for the amino group, and R3 acts as a leaving group. R1 represents an arylalkyl group, R2 represents a carboxyl group, and R3 represents a p-tosyloxy, methane sulfonyloxy or trifluoromethane sulfonyloxy or bromine. The final purification of the product is using a separation column, which is very convenient for automated synthesis. The invention uses the precursor with the chemical structures as in Formula 1. Formula 1 : Synthesis precursors for O-(2-C18F]fluoroethyl)-L-Tyrosine.

RADIOACTIVE TYROSINE DERIVATIVE, METHOD FOR PRODUCING SAME, LABELING AGENT FOR POSITRON IMAGING AND MEDICAL AGENT FOR ASSESSING GRADE OF MALIGNANCY OF TUMOR RESPECTIVELY COMPOSED OF RADIOACTIVE TYROSINE DERIVATIVE, AND METHOD FOR DETECTING TUMOR

It is intended to provide a radioactive tyrosine derivative represented by the formula (I) or a pharmaceutically acceptable salt thereof: wherein R 1 represents a group selected from the group consisting of- 11 CH 3 , - 11 CH 2 CH 3 , -CH 2 18 F, and -CH

Convenient method for the preparation of no-carrier-added O-(2-[18F]fluoroethyl)-L-tyrosine)

This is a novel method for production of no-carrier-added O-(2-[18F]fluoroethyl)-L-Tyrosine, which has been proved a suitable PET (position emission tomography) probe for tumor diagnosis imaging, and the preparation of the title compound starts from precursors with the chemical structures as in Formula 1, wherein R1 is a protective group for the carboxyl functional group, R2 is a protective group for the amino group, and R3 acts as a leaving group, R1 represents an arylalkyl group, R2 represents a carboxyl group, and R3 represents a p-tosyloxy, methane sulfonyloxy or trifluoromethane sulfonyloxy or bromine, and the final purification of the product is using a separation column, which is very convenient for automated synthesis, and the invention uses the precursor with the chemical structures as in Formula 1.