Synthesis and Autoradiography of Novel F-18 Labeled Reversible Radioligands for Detection of Monoamine Oxidase B.

Monoamine oxidase B (MAO-B) is an important enzyme regulating the levels of monoaminergic neurotransmitters. Selective MAO-B inhibitors have been labeled with carbon-11 or fluorine-18 to visualize the localization of MAO-B in vivo by positron emission tomography (PET) and thereby have been useful for studying neurodegenerative diseases. The aim of this study was to develop promising fluorine-18 labeled reversible MAO-B PET radioligands and their biological evaluation in vitro by autoradiography. Radiolabeling was achieved by classical one-step fluorine-18 nucleophilic substitution reaction. The stability and radiochemical yield was analyzed with HPLC. All five fluorine-18 labeled compounds were tested in human whole hemisphere autoradiography experiments. Five compounds (GEH200439, GEH200448, GEH200449, GEH200431A, and GEH200431B) were successfully radiolabeled with fluorine-18, and the incorporation yield of the fluorination reactions varied from 10 to 45% depending on the compound. The radiochemical purity was higher than 99% for all at the end of synthesis. Radioligands were found to be stable, with a radiochemical purity of >99% in a sterile phosphate buffered saline (pH = 7.4) over the duration of the study. The ARG binding density of only 18F-GEH200449 was consistent with known MAO-B expression in the human brain. Radiolabeling of five new fluorine-18 MAO-B reversible inhibitors was successfully accomplished. Compound 18F-GEH200449 binds specifically to MAO-B in vitro postmortem brain and could be a potential candidate for in vivo PET investigation.

Dopamine transporter neuroimaging accurately assesses the maturation of dopamine neurons in a preclinical model of Parkinson's disease.

BACKGROUND: Significant developments in stem cell therapy for Parkinson's disease (PD) have already been achieved; however, methods for reliable assessment of dopamine neuron maturation in vivo are lacking. Establishing the efficacy of new cellular therapies using non-invasive methodologies will be critical for future regulatory approval and application. The current study examines the utility of neuroimaging to characterise the in vivo maturation, innervation and functional dopamine release of transplanted human embryonic stem cell-derived midbrain dopaminergic neurons (hESC-mDAs) in a preclinical model of PD. METHODS: Female NIH RNu rats received a unilateral stereotaxic injection of 6-OHDA into the left medial forebrain bundle to create the PD lesion. hESC-mDA cell and sham transplantations were carried out 1 month post-lesion, with treated animals receiving approximately 4 × 105 cells per transplantation. Behavioural analysis, [18F]FBCTT and [18F]fallypride microPET/CT, was conducted at 1, 3 and 6 months post-transplantation and compared with histological characterisation at 6 months. RESULTS: PET imaging revealed transplant survival and maturation into functional dopaminergic neurons. [18F]FBCTT-PET/CT dopamine transporter (DAT) imaging demonstrated pre-synaptic restoration and [18F]fallypride-PET/CT indicated functional dopamine release, whilst amphetamine-induced rotation showed significant behavioural recovery. Moreover, histology revealed that the grafted cells matured differently in vivo producing high- and low-tyrosine hydroxylase (TH) expressing cohorts, and only [18F]FBCTT uptake was well correlated with differentiation. CONCLUSIONS: This study provides further evidence for the value of in vivo functional imaging for the assessment of cell therapies and highlights the utility of DAT imaging for the determination of early post-transplant cell maturation and differentiation of hESC-mDAs.

FASTlab Radiosynthesis of the 18 F-labelled HER2-binding Affibody molecule [18 F]GE-226.

An 18 F-labelled human epidermal growth factor receptor (HER2) receptor binding radiotracer is a potential tool to non-invasively identify HER2 positive tumour lesions in subjects with recurrent metastatic breast cancer. Having explored the manual radiochemistry to conjugate the Affibody molecule ZHER2:2891 with [18 F]4-fluorobenzaldehyde, we have developed and optimised a full protocol for the automated GE FASTlab synthesiser. Our chemometric model predicted the best radiochemical purity for a short conjugation time (2.8 minutes), a low temperature (65°C), and a medium Affibody molecule precursor amount (5.5 mg). Under these optimised conditions, [18 F]GE-226 was produced after solid-phase extraction purification with activity yield of 30% ± 7 (n = 18) and a radiochemical purity of 94% ± 2 (n = 18). The synthesis and purification was complete after 43 minutes and provided apparent molar activities of 12 to 30 GBq/µmol (n = 12) at the end of synthesis.

Exploring transition metal fluoride chelates - synthesis, properties and prospects towards potential PET probes.

The coordination chemistry of the first row transition metal trifluorides with terpy (2,2':6',2''-terpyridine) and Me3-tacn (1,4,7-trimethyl-1,4,7-triazacyclononane) was explored to identify potential systems for 18F radiolabelling. The complexes [MF3(L)] (M = Cr, Mn, Fe, Co; L = Me3-tacn, terpy) were synthesised and fully characterised by UV-vis and IR spectroscopy, microanalysis, and, for the diamagnetic [CoF3(L)], using 1H, 19F{1H} and 59Co NMR spectroscopy. Single crystal X-ray analyses are reported for [MF3(Me3-tacn)] (M = Mn, Co), [FeF3(terpy)] and [FeF3(BnMe2-tacn)]. Stability tests on [MF3(Me3-tacn)] (M = Cr, Mn, Fe) and [M'F3(terpy)] (M' = Cr, Fe) were performed and Cl/19F halide exchange reactions on [CrCl3(Me3-tacn)] using [Me4N]F in anhydrous MeCN solution, and [FeCl3(Me3-tacn)] using [Me4N]F in anhydrous MeCN or KF in aqueous MeCN solution were also carried out. Halide exchange reactions proved to be successful in forming [FeF3(Me3-tacn)] in aqueous MeCN solution within 30 minutes. Based upon the clean Cl/F exchange and the good stability observed for [FeF3(Me3-tacn)] in a range of competitive media, this was identified as a possible candidate for radiolabelling. 18F/19F isotopic exchange was achieved by addition of [18F]F- in the cyclotron target water to a MeCN solution of the benzyl-substituted analogue, [FeF3(BnMe2-tacn)], at a range of concentrations down to 24 nM with heating to 80 °C for 10 min.; the resulting [Fe18F19F2(BnMe2-tacn)] shows radiochemical purity (RCP) ≥90% after 2 h in a range of formulations, including 10% EtOH/phosphate buffered saline (PBS) and 10% EtOH/human serum albumin (HSA). This is the first reported complex with a transition metal directly bonded to [18F]F-.

Influence of transport line material on the molar activity of cyclotron produced [18F]fluoride.

INTRODUCTION: Production of fluorine-18-labeled radiopharmaceuticals is always associated with the varying levels of the same compound containing stable fluorine-19. In practice, this affects the molar activity (Am), defined as amount of radioactivity divided by the molar quantity (Bq/mol). We have focused on studying how the material of the transport tubing connecting the cyclotron target chamber to the synthesis device affects the concentration of fluoride in the water arriving to the reaction vessel and subsequently the Am of the fluorine-18 labeled radiopharmaceuticals produced. METHODS: Batches of irradiated and non-irradiated water were analyzed for fluoride content after being transported via non-fluorinated (PEEK, PP) and fluorinated (PTFE, ETFE) tubing or using no tubing at all. Am for the [18F]fluoride was determined and compared with the Am of [18F]fluciclatide, synthesized from the same [18F]fluoride containing batches of water. RESULTS: Significantly higher concentrations of fluoride were seen in irradiated water that was transported in fluorinated tubing compared to non-irradiated water transported in tubing of the same material. This elevation of fluoride concentration is presumably caused by the interaction of ionizing radiation with the fluorinated tubing used between the target chamber and hot cell. Likewise, a significant difference was seen for PEEK tubing (non-fluorinated). This could be due to the fact that fluorine containing compounds are used in the manufacture of PEEK. When using fluorinated tubing for transport of the irradiated water, the resulting fluciclatide concentrations were significantly higher compared to when using non-fluorinated tubing. No significant difference was seen between fluciclatide concentrations when PTFE or ETFE tubing was compared to each other. Using no tubing resulted in lowest fluciclatide concentration. CONCLUSIONS: Fluorinated tubing is a source of stable fluoride, and Am can be increased by using non-fluorinated transport tubing. Of all the tubing materials studied PP is preferred.

Rapid Aqueous Late-Stage Radiolabelling of [GaF3 (BnMe2 -tacn)] by 18 F/19 F Isotopic Exchange: Towards New PET Imaging Probes.

A simple and rapid method for 18 F radiolabelling of [GaF3 (BnMe2 -tacn)] by 18 F/19 F isotopic exchange is described. The use of MeCN/H2 O or EtOH/H2 O (75:25) and aqueous [18 F]F- (up to 200 MBq) with heating (80 °C, 10 min) gave 66±4 % 18 F incorporation at a concentration of 268 nm, and 37±5 % 18 F incorporation at even lower concentration (27 nm), without the need for a Lewis acid promoter. A solid-phase extraction method was established to give [Ga18 F19 F2 (BnMe2 -tacn)] in 99 % radiochemical purity in an EtOH/H2 O mixture.

Group 3 metal trihalide complexes with neutral N-donor ligands - exploring their affinity towards fluoride.

Fluorination of [ScCl3(Me3-tacn)] (Me3-tacn = 1,4,7-trimethyl-1,4,7-triazacyclononane) and [ScCl3(BnMe2-tacn)] (BnMe2-tacn = 1,4-dimethyl-7-benzyl-1,4,7-triazacyclononane) by Cl/F exchange with 3 mol. equiv. of anhydrous [NMe4]F in CH3CN solution yields the corresponding [ScF3(R3-tacn)] (R3 = Me3 or BnMe2). These are the first examples of scandium fluoride complexes containing neutral co-ligands. The fluorination occurs stepwise, and using a deficit of [NMe4]F produced [ScF2Cl(Me3-tacn)]. Attempts to fluorinate [YCl3(Me3-tacn)], [YI3(Me3-tacn)], [LaCl3(Me3-tacn)(OH2)] or [MCl3(terpy)] (M = Sc, Y or La; terpy = 2,2':6'2''-terpyridyl) using a similar method were unsuccessful, due to the Cl/F exchange being accompanied by loss of the neutral ligand from the metal centre. Fluorination of [ScCl3(Me3-tacn)] or [ScCl3(terpy)] with Me3SnF was also successful. The products were identified as the very unusual heterobimetallic [Sc(Me3-tacn)F2(µ-F)SnMe3Cl] and [Sc(terpy)F(µ-F)2(SnMe3Cl)2], in which the Me3SnCl formed in the reaction behaves as a weak Lewis acid towards the scandium fluoride complex, linked by Sc-F-Sn bridges. [Sc(terpy)F(µ-F)2(SnMe3Cl)2] decomposes irreversibly in solution but, whilst multinuclear NMR data show that [Sc(Me3-tacn)F2(µ-F)SnMe3Cl] is dissociated into the [ScF3(Me3-tacn)] and Me3SnCl in CH3CN solution, the bimetallic complex reforms upon evaporation of the solvent. The new scandium fluoride complexes and the chloride precursors have been characterised by microanalysis, IR and multinuclear NMR (1H, 19F, 45Sc) spectroscopy as appropriate. X-ray crystal structures provide unambiguous evidence for the identities of [Sc(Me3-tacn)F2(µ-F)SnMe3Cl], [ScF2Cl(Me3-tacn)], [YI3(Me3-tacn)], [{YI2(Me3-tacn)}2(µ-O)], [ScCl3(terpy)], [YCl3(terpy)(OH2)], and [{La(terpy)(OH2)Cl2}2(µ-Cl)2]. Once formed, the [ScF3(R3-tacn)] complexes are stable in water and unaffected by a ten-fold excess of Cl- or MeCO2-, although they are immediately decomposed by excess F-. The potential use of [ScF3(R3-tacn)] type complexes as platforms for 18F PET (positron emission tomography) radiopharmaceuticals is briefly discussed. Attempts to use the Group 3 fluoride "hydrates", MF3·xH2O, as precursors were unsuccessful; no reaction with R3-tacn or terpy occurred either on reflux in CH3CN or under hydrothermal conditions (H2O, 180° C, 15 h). PXRD data showed that these "hydrates" actually contain the anhydrous metal trifluorides with small amounts of surface or interstitial water.

A one-pot radioiodination of aryl amines via stable diazonium salts: preparation of 125I-imaging agents.

An operationally simple, one-pot, two-step tandem procedure that allows the incorporation of radioactive iodine into aryl amines via stable diazonium salts is described. The mild conditions are tolerant of various functional groups and substitution patterns, allowing late-stage, rapid access to a wide range of 125I-labelled aryl compounds and SPECT radiotracers.

[AlCl3(BnMe2-tacn)] - a new metal chelate scaffold for radiofluorination by Cl/F exchange.

Radiofluorination of a 2.63 µM solution (pH 4, NaOAc buffer) of [AlCl3(BnMe2-tacn)] via treatment with 2.99 mol. equiv. of [19F]KF doped with cyclotron-produced [18F]F- target water, with heating to 80-100 °C for 1 h, gives up to 24% 18F incorporation. SPE purification of the [Al19F218F(BnMe2-tacn)] radio-product gives >99% RCP, with excellent stability (>99% RCP after 3 h).

Organomediated Enantioselective (18)F†Fluorination for PET Applications.

The first organomediated asymmetric (18)F fluorination has been accomplished using a chiral imidazolidinone and [(18)F]N-fluorobenzenesulfonimide. The method provides access to enantioenriched (18)F-labeled α-fluoroaldehydes (>90% ee), which are versatile chiral (18)F synthons for the synthesis of radiotracers. The utility of this process is demonstrated with the synthesis of the PET (positron emission tomography) tracer (2S,4S)-4-[(18)F]fluoroglutamic acid.

Hydrothermal synthesis of Group 13 metal trifluoride complexes with neutral N-donor ligands.

The reactions of the hydrated Group 13 fluorides, MF3·3H2O (M = Al, Ga or In) with 2,2':6',2''-terpyridyl, 2,2'-bipyridyl or 1,10-phenanthroline under hydrothermal conditions (180 °C/15 h) produced high yields of the complexes [MF3(terpy)]·3H2O, [MF3(bipy)(OH2)]·2H2O and [MF3(phen)(OH2)]. X-Ray crystal structures of [M'F3(terpy)]·3H2O (M' = Al or Ga), [M'F3(bipy)(OH2)]·2H2O and [GaF3(phen)(OH2)] show that all of them contain distorted octahedral geometries at the metal with mer-trifluoride coordination. Extensive H-bonding (FH-OH) links the molecules. The complexes have been further characterised by microanalysis, IR, (1)H, (19)F{(1)H} and (27)Al NMR spectroscopy. In contrast, reactions of the trifluorides with the acyclic triamine, N,N,N',N',N''-pentamethyldiethylenetriamine, under similar hydrothermal conditions results in cleavage of the triamine and ring-closure to form the 1,1,4-trimethylpiperazinium cation, [⊂Me2N(CH2)2NMe(CH2)2](+), with fluorometallate anions, and confirmed by X-ray analysis of [⊂Me2N(CH2)2NMe(CH2)2]2[Al2F8(OH2)2]·2H2O. The strongly H-bonded [GaF3(terpy)]·3H2O was also obtained by Cl/F exchange from [GaCl3(terpy)] and [NBu4]F or [K(2,2,2-crypt)]F. Crystallisation of a mixture of [NH4][PF6] and [GaF3(terpy)]·3H2O from aqueous solution produced the edge-bridged cationic complex, [{Ga(terpy)F}2(µ-F)2][PF6]2. The synthesis of the more sterically bulky [GaCl3((t)Bu3-terpy)] ((t)Bu3-terpy = 4,4'4''-tris-(t)Bu-2,2':6',2''-terpyridyl) and the crystal structure of [GaCl2((t)Bu3-terpy)][GaCl4], which contains a trigonal bipyramidal cation, are also reported.

Radiofluorination of a pre-formed gallium(III) aza-macrocyclic complex: towards next-generation positron emission tomography (PET) imaging agents.

As part of a study to investigate the factors influencing the development of new, more effective metal-complex-based positron emission tomography (PET) imaging agents, the distorted octahedral complex, [GaCl(L)]⋅2 H2O has been prepared by reaction of 1-benzyl-1,4,7-triazacyclononane-4,7-dicarboxylic acid hydrochloride (H2L⋅HCl) with Ga(NO3)3⋅9 H2O, which is a convenient source of Ga(III) for reactions in water. Spectroscopic and crystallographic data for [GaCl(L)]⋅2 H2O are described, together with the crystal structure of [GaCl(L)]⋅MeCN. Fluorination of this complex by Cl(-)/F(-) exchange was achieved in high yield by treatment with KF in water at room temperature over 90 minutes, although the reaction was complete in approximately 30 minutes if heated to 80 °C, giving [GaF(L)]⋅2 H2O in good yield. The same complex was obtained by hydrothermal synthesis from GaF3⋅3 H2O and Li2L, and has been characterised by single-crystal X-ray analysis, IR, (1)H and (19)F{(1)H} NMR spectroscopy and ESI(+) MS. Radiofluorination of the pre-formed [GaCl(L)]⋅2 H2O has been demonstrated on a 210 nanomolar scale in aqueous NaOAc at pH 4 by using carrier-free (18)F(-), leading to 60-70% (18)F-incorporation after heating to 80 °C for 30 minutes. The resulting radioproduct was purified easily by using a solid-phase extraction (SPE) cartridge, leading to 98-99% radiochemical purity. The [Ga(18)F(L)] is stable for at least 90 minutes in 10% EtOH/NaOAc solution at pH 6, but defluorinates over this time scale at pH of approximately 7.5 in phosphate buffered saline (PBS) or human serum albumin (HSA). The subtle role of the Group 13 metal ion and co-ligand donor set in influencing the pH dependence of this system is discussed in the context of developing potential new imaging agents for PET.

(99m)Tc SPECT imaging agent based on cFLFLFK for the detection of FPR1 in inflammation.

Non-invasive imaging of the inflammatory process can provide great insight into a wide variety of disease states, aiding diagnosis, evaluation and effective targeted treatment. During inflammation, blood borne leukocytes are recruited, through a series of activation and adhesion steps, to the site of injury or infection where they migrate across the blood vessel wall into the tissue. Thus, tracking leukocyte recruitment and accumulation provides a dynamic and localised read out of inflammatory events. Current leukocyte imaging techniques require ex vivo labelling of patient blood, involving laborious processing and potential risks to both patient and laboratory staff. Utilising high affinity ligands for leukocyte specific receptors may allow for injectable tracers that label leukocytes in situ, omitting potentially hazardous ex vivo handling. Formyl peptide receptors (FPRs) are a group of G-protein coupled receptors involved in the chemotaxis and inflammatory functioning of leukocytes. Highly expressed on leukocytes, and up-regulated during inflammation, these receptors provide a potential target for imaging inflammatory events. Herein we present the synthesis and initial in vitro testing of a potential Single Photon Emission Computed Tomography (SPECT) leukocyte tracer. The FPR1 antagonist cFLFLFK-NH2, which displays high affinity with little physiological effect, has been linked via a PEG motif to a (99m)Tc chelate. This tracer shows in vitro binding to human embryonic kidney cells expressing the FPR1 receptor, and functional in vitro tests reveal cFLFLFK-NH2 compounds to have no effect on inflammatory cell functioning. Overall, these data show that (99m)Tc.cFLFLFK-NH2 may be a useful tool for non-invasive imaging of leukocyte accumulation in inflammatory disease states.

[GaF3(BzMe2-tacn)]--a neutral 'metalloligand' towards alkali metal and ammonium cations in water.

The neutral complex, [GaF3(L)] (L = 1-benzyl-4,7-dimethyl-1,4,7-triazacyclononane, BzMe2-tacn), acts as a 'metalloligand' to Na(+), K(+) and [NH4](+) cations in aqueous solution, forming supramolecular assemblies containing significant Na/K-F and H3N(+)H···F coordination. κ(1)-[BF4](-) and κ(2)-[PF6](-) coordination is also evident to Na(+) and K(+), respectively.

Initial evaluation of 18F-GE-179, a putative PET Tracer for activated N-methyl D-aspartate receptors.

UNLABELLED: N-methyl D-aspartate (NMDA) ion channels play a key role in a wide range of physiologic (e.g., memory and learning tasks) and pathologic processes (e.g., excitotoxicity). To date, suitable PET markers of NMDA ion channel activity have not been available. (18)F-GE-179 is a novel radioligand that selectively binds to the open/active state of the NMDA receptor ion channel, displacing the binding of (3)H-tenocyclidine from the intrachannel binding site with an affinity of 2.4 nM. No significant binding was observed with 10 nM GE-179 at 60 other neuroreceptors, channels, or transporters. We describe the kinetic behavior of the radioligand in vivo in humans. METHODS: Nine healthy participants (6 men, 3 women; median age, 37 y) each underwent a 90-min PET scan after an intravenous injection of (18)F-GE-179. Continuous arterial blood sampling over the first 15 min was followed by discrete blood sampling over the duration of the scan. Brain radioactivity (KBq/mL) was measured in summation images created from the attenuation- and motion-corrected dynamic images. Metabolite-corrected parent plasma input functions were generated. We assessed the abilities of 1-, 2-, and 3-compartment models to kinetically describe cerebral time-activity curves using 6 bilateral regions of interest. Parametric volume-of-distribution (V(T)) images were generated by voxelwise rank-shaping regularization of exponential spectral analysis (RS-ESA). RESULTS: A 2-brain-compartment, 4-rate-constant model best described the radioligand's kinetics in normal gray matter of subjects at rest. At 30 min after injection, 37% of plasma radioactivity represented unmetabolized (18)F-GE-179. The highest mean levels of gray matter radioactivity were seen in the putamina and peaked at 7.5 min. A significant positive correlation was observed between K1 and V(T) (Spearman ρ = 0.398; P = 0.003). Between-subject coefficients of variation of V(T) ranged between 12% and 16%. Voxelwise RS-ESA yielded similar V(T)s and coefficients of variation. CONCLUSION: (18)F-GE-179 exhibits high and rapid brain extraction, with a relatively homogeneous distribution in gray matter and acceptable between-subject variability. Despite its rapid peripheral metabolism, quantification of (18)F-GE-179 VT is feasible both within regions of interest and at the voxel level. The specificity of (18)F-GE-179 binding, however, requires further characterization with in vivo studies using activation and disease models.

Catalytic decarboxylative fluorination for the synthesis of tri- and difluoromethyl arenes.

Treatment of readily available α,α-difluoro- and α-fluoroarylacetic acids with Selectfluor under Ag(I) catalysis led to decarboxylative fluorination. This operationally simple reaction gave access to tri- and difluoromethylarenes applying a late-stage fluorination strategy. Translation to [(18)F]labeling is demonstrated using [(18)F]Selectfluor bis(triflate), a reagent affording [(18)F]tri- and [(18)F]difluoromethylarenes not within reach with [(18)F]F2.

Exploration of the structure-activity relationship of a novel tetracyclic class of TSPO ligands-potential novel positron emitting tomography imaging agents.

A series of novel TSPO ligands based on the tetracyclic class of translocator protein (TSPO) ligands first described by Okubo et al. was synthesised and evaluated as potential positron emitting tomography (PET) ligands for imaging TPSO in vivo. Fluorine-18 labelling of the molecules was achieved using direct radiolabelling or synthon based labelling approaches. Several of the ligands prepared have promising profiles as potential TSPO PET imaging ligands.

Radiosynthesis of the D2/3 agonist [3-11C]-(+)-PHNO using [11C]iodomethane.

We report here a radiosynthesis for the D(2/3) agonist (+)-4-([3-(11)C]propyl)-3,4,4a,5,6,10b-hexahydro-2H-naphtho[1,2-b][1,4]oxazin-9-ol (3-[(11)C]-(+)-PHNO) labelled at the terminal carbon of the N-propyl chain. The protocol is based on (11)C-methylation of an N-acetyl precursor. This initial step is followed by a reduction with LiAlH(4) to give ([3-(11)C]-(+)-PHNO). We first applied the method for the synthesis of a model compound, N-3-([(11)C]propyl)-1,2,3,4-tetrahydroisoquinoline, which we obtained in 77-97% analytical radiochemical yield (n=6) in 20 min. Similarly, we prepared ([3-(11)C]-(+)-PHNO) in 55-60% analytical radiochemical yield (n=5) using a one-pot procedure. We have also been able to implement the complete process on a semi-automated module. This platform delivered purified and formulated [3-(11)C]PHNO with an average radiochemical yield of 9% (n=13, range 2-30%, non-decay corrected), a radiochemical purity >95%, and a specific radioactivity of 26.8-81.1 GBq/µmol in a total time of 63-65 min.

[18F]fluorination of an arylboronic ester using [18F]selectfluor bis(triflate): application to 6-[18F]fluoro-L-DOPA.

The Ag-mediated electrophilic [(18)F]fluorination of an arylboronic ester is reported. This new radiochemical transformation uses [(18)F]selectfluor bis(triflate) in acetone. The process gave 6-[(18)F]fluoro-L-DOPA with a RCY of 19 ± 12% and a specific activity of 2.6 ± 0.3 GBq µmol(-1).

Gd3+ cFLFLFK conjugate for MRI: a targeted contrast agent for FPR1 in inflammation.

Formyl Peptide Receptors (FPRs) are vital in the host inflammatory response, playing an important regulatory role in multiple diseases. A Gd(III) DOTA conjugate of cFLFLFK has been synthesised which targets and visualises FPR1 upon leukocytes in the inflammatory response via magnetic resonance imaging for the first time.