Electrochemical transfer of [18F]fluoride from [18O]water into organic solvents ready for labeling reactions

For labeling reactions [¹⁸F]fluoride has to be separated from [¹⁸O]water and transferred into an organic solvent suitable for nucleophilic substitutions. An electrolytical method is described for depositing [¹⁸F]fluoride on a vitreous carbon electrode and releasing it directly into CH₃CN or DMSO. In the presence of Et₃N×3HF, [¹⁸F]fluoride is almost quantitatively released into acetonitrile. When using n.c.a conditions, i.e., Et₃N^.HCl, desorption of the ¹⁸F activity is almost 70% and 60% in acetonitrile and DMSO, respectively, already within 5 minutes.     

Nucleophilic aromatic substitution by [<Superscript>18</Superscript>F]fluoride at substituted 2-nitropyridines

For the radiofluorination of benzenes and benzene derivatives, the electrophilic reaction with [¹⁸F]F₂ is a very common route. Yet, aromatic nucleophilic substitution (S_NAr) by n.c.a [¹⁸F]fluoride, which can be produced efficiently in high amounts, has been considered to be very desirable. However, to facilitate ¹⁸F-labelling via S_NAr at an electron rich aromatic system, an appropriate leaving group must be present together with an auxiliary group in ortho or para position to the leaving group. An interesting alternative for the auxiliary group is the heteroatom of a heteroaromatic system, for which pyridine is a leading example. Dolci et al. (J Label Compd Radiopharm 42:975–985, 1999) have evaluated the scope of the nucleophilic aromatic fluorination of 2-substituted pyridine rings using the activated K [¹⁸F]F-K₂₂₂ complex. As methyl and methoxy groups are known to enhance the electron density of an aromatic system by the +I and the +M effect, respectively, S_NAr is unlikely to occur. Until now, the effect of these substituents has not been studied towards the ¹⁸F-radiofluorination of substituted 2-nitropyridines by use of [¹⁸F]fluoride. Therefore, we have investigated the effect of methoxy and methyl groups in 2-nitropyridines. The results showed that 3-methoxy-2-nitropyridine and 3-methyl-2-nitropyridine can efficiently be substituted by [¹⁸F]fluoride with high RCY’s (70–89%) in short reaction times (1–30 min) at a reaction temperature of 140 °C. Moreover, 3-methoxy-6-methyl-2-[¹⁸F]fluoropyridine was obtained from the corresponding nitro-precursor in a high yield of 81 ± 1% after 30 min at 140 °C. In case of 2-nitropyridines data indicates the effect of methyl and methoxy groups on S_NAr to be of minor importance.     

Synthesis of [F]xenon difluoride as a radiolabeling reagent from [F]fluoride ion in a micro-reactor and at production scale

[¹⁸F]Xenon difluoride ([¹⁸F]XeF₂), was produced by treating xenon difluoride with cyclotron-produced [¹⁸F]fluoride ion to provide a potentially useful agent for labeling novel radiotracers with fluorine-18 (t_1/2 = 109.7 min) for imaging applications with positron emission tomography. Firstly, the effects of various reaction parameters, for example, vessel material, solvent, cation and base on this process were studied at room temperature. Glass vials facilitated the reaction more readily than polypropylene vials. The reaction was less efficient in acetonitrile than in dichloromethane. Cs⁺ or K⁺ with or without the cryptand, K 2.2.2, was acceptable as counter cation. The production of [¹⁸F]XeF₂ was retarded by K₂CO₃, suggesting that generation of hydrogen fluoride in the reaction milieu promoted the incorporation of fluorine-18 into xenon difluoride. Secondly, the effect of temperature was studied using a microfluidic platform in which [¹⁸F]XeF₂ was produced in acetonitrile at elevated temperature (≥85 °C) over 94 s. These results enabled us to develop a method for obtaining [¹⁸F]XeF₂ on a production scale (up to 25 mCi) through reaction of [¹⁸F]fluoride ion with xenon difluoride in acetonitrile at 90 °C for 10 min. [¹⁸F]XeF₂ was separated from the reaction mixture by distillation at 110 °C. Furthermore, [¹⁸F]XeF₂ was shown to be reactive towards substrates, such as 1-((trimethylsilyl)oxy)cyclohexene and fluorene.     

Sulfonyl Fluoride‐Based Prosthetic Compounds as Potential 18F Labelling Agents

Nucleophilic incorporation of [¹⁸F]F^? under aqueous conditions holds several advantages in radiopharmaceutical development, especially with the advent of complex biological pharmacophores. Sulfonyl fluorides can be prepared in water at room temperature, yet they have not been assayed as a potential means to ¹⁸F‐labelled biomarkers for PET chemistry. We developed a general route to prepare bifunctional 4‐formyl‐, 3‐formyl‐, 4‐maleimido‐ and 4‐oxylalkynl‐arylsulfonyl [¹⁸F]fluorides from their sulfonyl chloride analogues in 1:1 mixtures of acetonitrile, THF, or tBuOH and Cs[¹⁸F]F/Cs₂CO_3(aq.) in a reaction time of 15 min at room temperature. With the exception of 4‐N‐maleimide‐benzenesulfonyl fluoride ( 3 ), pyridine could be used to simplify radiotracer purification by selectively degrading the precursor without significantly affecting observed yields. The addition of pyridine at the start of [¹⁸F]fluorination (1:1:0.8 tBuOH/Cs₂CO_3(aq.)/pyridine) did not negatively affect yields of 3‐formyl‐2,4,6‐trimethylbenzenesulfonyl [¹⁸F]fluoride ( 2 ) and dramatically improved the yields of 4‐(prop‐2‐ynyloxy)benzenesulfonyl [¹⁸F]fluoride ( 4 ). The N‐arylsulfonyl‐4‐dimethylaminopyridinium derivative of 4 ( 14 ) can be prepared and incorporates ¹⁸F efficiently in solutions of 100 % aqueous Cs₂CO₃ (10 mg mL^?1). As proof‐of‐principle, [¹⁸F] 2 was synthesised in a preparative fashion [88(±8) % decay corrected (n=6) from start‐of‐synthesis] and used to radioactively label an oxyamino‐modified bombesin(6–14) analogue [35(±6) % decay corrected (n=4) from start‐of‐synthesis]. Total preparation time was 105–109 min from start‐of‐synthesis. Although the ¹⁸F‐peptide exhibited evidence of proteolytic defluorination and modification, our study is the first step in developing an aqueous, room temperature ¹⁸F labelling strategy.     

A facile direct nucleophilic synthesis of O-(2-[18F]fluoroethyl)-l-tyrosine ([18F]FET) without HPLC purification

Due to favourable in vivo characteristics, its high specificity and the longer half-life of ¹⁸F (109.8 min) allowing for remote-site delivery, O-(2-[¹⁸F]fluoroethyl)-l-tyrosine ([¹⁸F]FET) has gained increased importance for molecular imaging of cerebral tumors. Consequently, the development of simple and efficient production strategies for [¹⁸F]FET could be an important step to further improve the cost-effective availability of [¹⁸F]FET in the clinical environment. In the present study [¹⁸F]FET was synthesized via direct nucleophilic synthesis using an earlier developed chiral precursor, the Ni^II complex of an alkylated (S)-tyrosine Schiff base, Ni-(S)-BPB-(S)-Tyr-OCH₂CH₂OTs. The purification method has been developed via solid phase extraction thereby omitting cumbersome HPLC purification. The suggested SPE purification using combination of reverse phase and strong cation exchange cartridges provided [¹⁸F]FET in high chemical, radiochemical and enantiomeric purity and 35 % radiochemical yield (decay-corrected, 45 min synthesis time). The method was successfully automated using a commercially available synthesis module, Scintomics Hotbox^one. Based on the current results, the proposed production route appears to be well suited for transfer into an automated cassette-type radiosynthesizers without using HPLC.     

Electrochemical radiofluorination: Labeling of benzene with [18F]fluoride by nucleophilic substitution

¹⁸F-labeling of aromatic compounds normally is achieved by electrophilic substitution. In that case [¹⁸F]fluoride cannot be applied although it is produced very efficiently at medical cyclotrons. By the use of electrochemical methods, however, benzene can be oxidized and thus, the electron density is reduced in a way that nucleophilic attack of [¹⁸F]fluoride occurs. For the first time benzene was shown to be labeled with [¹⁸F]fluoride after being electrochemically oxidized in a 2 ml electrolysis cell with 0.033M Et₃N^.3HF and 0.066M Et₃N^.HCl in CH₃CN and benzene in various concentrations. After 50 Coulombs (60-90 min) maximum of labeling was reached. With the highest concentration of aromatic compound (1.0M) the radiochemical yields were 16±9% with specific activities up to 27 GBq/mmol.     

Difluorocarbene‐Derived Trifluoromethylthiolation and [18F]Trifluoromethylthiolation of Aliphatic Electrophiles

The first trifluoromethylthiolation and [¹⁸F]trifluoromethylthiolation of alkyl electrophiles with in situ generated difluorocarbene in the presence of elemental sulfur and external (radioactive) fluoride ion is described. This transition‐metal‐free approach is high yielding, compatible with a variety of functional groups, and operated under mild reaction conditions. The conceptual advantage of this exogenous‐fluoride‐mediated transformation enables unprecedented syntheses of [¹⁸F]CF₃S‐labeled molecules from most commonly used [¹⁸F]fluoride ions. The rapid radiochemical reaction time (≤1 min) and high functional‐group tolerance allow access to a variety of aliphatic [¹⁸F]CF₃S compounds in high yields.     

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.     

[F]Fluoroamines via ring-opening of N-Cbz-2-methylaziridine with [F]-fluoride

A highly regioselective method was developed for ring-opening benzyloxycarbonyl (Cbz)-protected 2-methylaziridine with [¹⁸F]-labelled fluoride. Following catalytic hydrogenation, 1-[¹⁸F]fluoro-2-propanamine ([¹⁸F]1) and 2-[¹⁸F]fluoro-1-propanamine ([¹⁸F]2) were prepared as the major and minor products, respectively (85:15), and were characterized following acylation with benzyl chloride. This methodology is applicable towards the generation of new [¹⁸F]-labelled amines for incorporation into radiopharmaceuticals.     

Synthesis of <Emphasis Type="Italic">O</Emphasis>-(2-[<Superscript>18</Superscript>F]fluoroethyl)-<Emphasis Type="Italic">L</Emphasis>-tyrosine and its biological evaluation in B16 melanoma-bearing mice as PET tracer for tumor imaging

O-(2-[¹⁸F]fluoroethyl)-L-tyrosine ([¹⁸F]FET), a fluorine-18 labeled analogue of tyrosine, has been synthesized and biologically evaluated in tumor-bearing mice. The whole synthesis procedure is completed within 50 min. The radiochemical yield is about 40% (no decay corrected) and radiochemical purity more than 97% after simplified solid phase extraction. [¹⁸F]FET shows rapid, high uptake and long retention in the tumor as well as low uptake in the brain. The ratios of tumor-to-muscle (T/M) and tumor-to-blood (T/B) of [¹⁸F]FET are similar to those of [¹⁸F]FDG, but the ratios of tumor-to-brain (T/Br) are 2–3 times higher than that of [¹⁸F]FDG. Autoradiography of [¹⁸F]FET demonstrates a remarkable accumulation in melanoma with high contrast. It appears to be a probable competitive candidate for melanoma imaging with PET. Supported by the Knowledge Innovation Project of Chinese Academy of Sciences (No. KJCX1-SW-08) and the National Natural Science Foundation of China (Grant No. 30371634)     

Autoradiolysis of the 2-deoxy-2-[<Superscript>18</Superscript>F]fluoro-D-glucose radiopharmaceutical

Summary To control virtually the toxic compounds and to improve quality control of the solution of 2-deoxy-2-[¹⁸F]fluoro-d-glucose (2-[¹⁸F]FDG), the products of its autoradiolysis were analyzed by high-performance liquid chromatography with electrospray mass spectrometric and radiometric detectors (HPLC/MS/RAD), thin layer chromatography on TLC silica plate and HPTLC on amino modified silica plate. Except Kryptofix^™ 2.2.2, glucose and fluoride anion, no by-products and impurities were observed by LC/MS analysis of fresh 2-[¹⁸F]FDG samples. The analysis performed in the time interval of 6 to 48 hours after the end of 2-[¹⁸F]FDG synthesis indicated that the activity of the autoradiolysis products separated by HPLC did not exceed 1.3%. As the main autoradiolysis products of 3.3 ^. 10^-5 to 4.4 ^. 10^-5M 2-[¹⁸F]FDG solution of original specific activity 0.5-1.5 GBq ^. cm^-3 were established: arabinose - 2.8 μM (G= 0.07/100 eV), gluconic and glucuronic acids 1.8-0.5 μM (G =0.01-0.05/100 eV), arabinose and araburonic acids occurred under 0.5 μM concentration at residual glucose contents about 0.14 mM. Radiation chemical yields of active products were calculated from molar activity of 2-[¹⁸F]FDG and the percentage of their activity: 0.5% radiochemical yield of 2-[¹⁸F]fluoroglucuronic acid corresponds to the G = 0.004/100 eV and 0.3% yield of 2-[¹⁸F]fluorogluconic acid issues G = 0.003/100 eV.     

The [F]2-Fluoro-1,3-thiazolyl Moiety - an Easily-Accessible Structural Motif for Prospective Molecular Imaging Radiotracers

2-Fluoro-1,3-thiazoles were rapidly and efficiently labeled with no-carrier-added fluorine-18 (t_1/2 = 109.7 min) by treatment of readily prepared 2-halo precursors with cyclotron-produced [¹⁸F]fluoride ion. The [¹⁸F]2-fluoro-1,3-thiazolyl moiety constitutes a new and easily-labeled structural motif for prospective molecular imaging radiotracers.     

Synthesis and Derivatization of 1,1‐[18F]Difluorinated Alkenes

A general method for the synthesis of 1,1‐[¹⁸F]difluorinated alkenes from [¹⁸F]fluoride is reported. This transformation is highly regioselective giving the desired ¹⁸F‐fluoroalkenes with radiochemical purities of up to 77 % within 20 minutes and a molar activity (A_m) of 1 GBq μmol^?1. The transformations are operationally simple to perform and were readily translated onto a commercial automated synthesis unit. The resultant 1,1‐[¹⁸F]difluorinated alkene motif is prevalent in numerous drug molecules, and this is the first general method to synthesize this motif with fluorine‐18. ¹⁸F‐fluorinated alkenes are excellent building blocks and participate in a number of post‐labeling transformations to access a range of ¹⁸F‐perfluorinated functional groups that have never before been radiolabeled with non‐carrier‐added [¹⁸F]fluoride. This method considerably expands the range of ¹⁸F‐motifs accessible to radiochemists.     

Module-assisted one-pot synthesis of [18F]SFB for radiolabeling proteins

The need of reliable production of N-succinimidyl 4-[¹⁸F]fluorobenzoate ([¹⁸F]SFB), a versatile ¹⁸F-labeled prosthetic group for protein labeling, has increased dramatically due to the easy availability of proteins or their engineered derivatives for targeted molecular imaging. A module-assisted radiosynthesis of [¹⁸F]SFB was developed using a three-step, one-pot procedure and ethyl 4-(trimethylammonium)benzoate triflate (1) as the starting material. The radiochemical transformations were carried out in a general-purpose, custom-made module and streamlined by an anhydrous deprotection strategy using t-BuOK/DMSO. After HPLC-purification, [¹⁸F]SFB was synthesized in radiochemical yields of 20–30% (n > 10, not decay-corrected) and excellent radiochemical and chemical purities (>98%). The total synthesis and purification time required is ~90 min. Using the purified [¹⁸F]SFB, three ¹⁸F-labeled proteins, bovine serum albumin (BSA), chicken egg albumin (CEA) and transferrin, were synthesized in yields of 61.0–79.5%. The ¹⁸F-Annexin V for apoptosis imaging was also produced in 5% radiolabeling yield and >95% radiochemical purity.     

Synthesis of para‐[18F]Fluorofenbufen Octylamide for PET Imaging of Brain Tumors

Glioma is a brain tumor associated with a poor therapeutic outcome with an average life expectancy of 14 months. Cyclooxygenase‐2 (COX‐2) expression is associated with the progression of the tumor and is considered a therapeutic target of chemo agents. Para‐[¹⁸F]Fluorofenbufen octylamide ([¹⁸F]FFOA) was obtained with the radiochemical yield of 16% and specific activity of 4 GBq/μmol, and the IC₅₀ values of COX‐1 and COX‐2 were 26.5 and 32.7 μM, respectively. The stability of cold FFOA in plasma was significantly improved with a half‐life of 30 min, and the uptake ratio of [¹⁸F]FFOA in rats with brain tumor was 1.5 as determined from accumulation of 3.9% injection dose (ID/g) in the brain tumor and 2.5% ID/g in the brain. [¹⁸F]FFOA with COX‐2 micromolar affinity can be used to differentiate between brain tumor and normal region.     

Synthesis of <Emphasis Type="Italic">O</Emphasis>-[2-[<Superscript>18</Superscript>F]fluoro-3-(2-nitro-1<Emphasis Type="Italic">H</Emphasis>-imidazole-1-yl)propyl]tyrosine ([<Superscript>18</Superscript>F]FNT]) as a new class of tracer for imaging hypoxia

For detection of hypoxic tumor tissue, all radiotracers synthesized until now, are based on the concept that cellular uptake is being controlled by diffusion. As a new approach, we chose the concept to have the tracer hypothetically transported into the cells by well known carrier systems like the amino acid transporters. For this purpose, radiosynthesis of O-[2-[¹⁸F]fluoro-3-(2-nitro-1H-imidazole-1yl)propyl]tyrosine ([¹⁸F]FNT]) was carried out from methyl 2-(benzyloxycarbonyl)-3-(4-3-(2-nitro-1H-imidazol-1-yl)-2-(tosyloxy)propoxy) phenyl)propanoate via no-carrier-added nucleophilic aliphatic substitution. After labelling, 81 ± 0.9% of labelled intermediate i.e. methyl 2-(benzyloxycarbonyl)-3-(4-(2-[¹⁸F]fluoro-3-(2-nitro-1H-imidazole-1-yl)propoxy) phenyl)propanoate was obtained at 140 °C. At the end of radiosynthesis, [¹⁸F]FNT was obtained in an overall radiochemical yield of 40 ± 0.9% (not decay corrected) within 90 min in a radiochemical purity of >98% in a formulation ready for application in the clinical studies for PET imaging of hypoxia.     

Assessment of labelled products with different radioanalytical methods: study on 18F-fluorination reaction of 4-[18F]fluoro-N-[2-[1-(2-methoxyphenyl)-1-piperazinyl]ethyl-N-2-pyridinyl-benzamide (p-[18F]MPPF)

The serotonin receptor 5-HT_1A ligand 4-[¹⁸F]fluoro-N-[2-[1-(2-methoxyphenyl)-1-piperazinyl]ethyl-N-2-pyridinyl-benzamide (p-[¹⁸F]MPPF) was produced by a simplified method of Le Bars et al. Traditional oil bath heating was compared to microwave heating. Various radioanalytical methods, radio-Thin Layer Chromatography (TLC), High Pressure Liquid Chromatography (HPLC) and Mass Spectrometry (MS), were compared in the evaluation of the labelled product(s). The crude reaction mixture consisted of p-[¹⁸F]MPPF and 2–4 radioactive by-products eluting after the product fraction, and the reverse-phase HPLC method failed occasionally to separate p-[¹⁸F]MPPF from the radioactive by-product with close retention time. The heating method had no significant effect on the composition of labelled by-products. In LC-(ESI)-MS analysis of p-[¹⁸F]MPPF the labelled product was identified with m/z ratio of 435 ([M + H⁺]). The other HPLC fractions were measured to have following m/z ratios: (1) 327; 349; (675) (2) 402; 407/408; (791) and (3) 436, suggesting different kind of decomposition of the labelled product and/or the inactive precursor. The ion trap mass spectrometer was sufficient for the qualitative analysis of p-[¹⁸F]MPPF. However, differentiation of by-products arising from the decomposition of p-[¹⁸F]MPPF or from its precursor p-MPPNO₂ proved to be challenging.     

Fully automated radiosynthesis of [<Superscript>18</Superscript>F]Fluoromisonidazole with single neutral alumina column purification: optimization of reaction parameters

1-H-1-(3-[¹⁸F]fluoro-2-hydroxypropyl)-2-nitroimidazole ([¹⁸F]FMISO), is the most used hypoxia-imaging agent in oncology and we have recently reported a fully automated procedure for its synthesis using the Nuclear Interface FDG module and a single neutral alumina column for purification. Using 1-(2′-nitro-1′-imidazolyl)-2-O-tetra-hydropyranyl-3-O-toluenesulfonylpropanediol (NITTP) as the precursor, we have investigated the yield of [¹⁸F]FMISO using different reaction times, temperatures, and the amount of precursor. The overall yield was 48.4 ± 1.2% (n = 3), (without decay correction) obtained using 10 mg NITTP with the radio-fluorination carried out at 145 °C for 3 min followed by acid hydrolysis for 3 min at 125 °C in a total synthesis time of 32 ± 1 min. Increasing the precursor amount to 25 mg did not improve the overall yield under identical reaction conditions, with the decay uncorrected yield being 46.8 ± 1.6% (n = 3), but rather made the production less economical. It was also observed that the yield increased linearly with the amount of NITTP used, from 2.5 to 10 mg and plateaued from 10 to 25 mg. Radio-fluorination efficiency at four different conditions was also compared. It was also observed by radio thin layer chromatography (radio-TLC) that the duration of radio-fluorination of NITTP, not the radio-fluorination temperature favoured the formation of labeled thermally degraded product, but the single neutral alumina column purification was sufficient enough to obtain [¹⁸F]FMISO devoid of any radiochemical as well as cold impurities.     

Clinical Relevance of [18F]Florbetaben and [18F]FDG PET/CT Imaging on the Management of Patients with Dementia

PET of β-Amyloid plaques (Aβ) using [¹⁸F]florbetaben ([¹⁸F]FBB) and [¹⁸F]fluorodeoxyglucose ([¹⁸F]FDG) increasingly aid clinicians in early diagnosis of dementia, including Alzheimer’s disease (AD), frontotemporal disease, dementia with Lewy bodies, and vascular dementia. The aim of this retrospective analysis was to evaluate clinical relevance of [¹⁸F]FBB, [¹⁸F]FDG PET and complimentary CSF measurements in patients with suspected dementia. In this study, 40 patients with clinically suspected or history of dementia underwent (1) measurement of Aβ peptides, total tau, and p-tau protein levels in the cerebrospinal fluid (CSF) compared with healthy controls (HC); (2) clinical and neuropsychological assessment, which included Consortium to Establish a Registry for Alzheimer’s Disease neuropsychological assessment battery (CERAD-NAB); (3) [¹⁸F]FBB and [¹⁸F]FDG PET imaging within an average of 3 weeks. The subjects were within 15 days stratified using PET, CSF measurements as HC, mild cognitive impaired (MCI) and dementia including Alzheimer´s disease. The predictive dementia-related cognitive decline values were supporting the measurements. PET images were evaluated visually and quantitatively using standard uptake value ratios (SUVR). Twenty-one (52.5%) subjects were amyloid-positive (Aβ+), with a median neocortical SUVR of 1.80 for AD versus 1.20 relative to the respective 19 (47.5 %) amyloid-negative (Aβ-) subjects. Moreover, the [¹⁸F]FDG and [¹⁸F]FBB confirmed within a sub-group of 10 patients a good complimentary role by correlation between amyloid pathology and brain glucose metabolism in 8 out of 10 subjects. The results suggest the clinical relevance for [¹⁸F]FBB combined with [¹⁸F]FDG PET retention and CFS measurements serving the management of our patients with dementia. Therefore, [¹⁸F]FBB combined with [¹⁸F]FDG PET is a helpful tool for differential diagnosis, and supports the patients’ management as well as treatment.     

Fully Automated Synthesis of Novel TSPO PET Imaging Ligand [18F]Fluoroethyltemazepam

Introduction: Benzodiazepines, including temazepam are described as TSPO antagonists. In fact, TSPO was initially described as a peripheral benzodiazepine receptor (PBR) with a secondary binding site for diazepam. TSPO is a potential imaging target of neuroinflammation because there is an amplification of the expression of this receptor. Objectives: Herein, we developed a novel fluorinated benzodiazepine ligand, [¹⁸F]Fluoroethyltemazepam ([¹⁸F]F-FETEM), for positron emission tomography (PET) imaging of translocator protein (18 kDa). Methods: [¹⁸F]F-FETEM was radiolabelled with an automated synthesizer via a one-pot procedure. We conducted a [¹⁸F]F-aliphatic nucleophilic substitution of a tosylated precursor followed by purification on C18 and Alumina N SPE cartridges. Quality control tests was also carried out. Results: We obtained 2.0–3.0% decay-uncorrected radiochemical activity yield (3.7% decay-corrected) within the whole synthesis time about 33 min. The radiochemical purity of [¹⁸F]F-FETEM was over 90% by TLC analysis. Conclusions: This automated procedure may be used as basis for future production of [¹⁸F]F-FETEM for preclinical PET imaging studies.