Synthesis,radiofluorination and first evaluation of (±)‐[18F]MDL 100907 as serotonin 5‐HT2A receptor antagonist for PET

In some psychiatric disorders 5‐HT_2A receptors play an important role. In order to investigate those in vivo there is an increasing interest in obtaining a metabolically stable, subtype selective and high affinity radioligand for receptor binding studies using positron emission tomography (PET). Combining the excellent in vivo properties of [¹¹C]MDL 100907 for PET imaging of 5‐HT_2A receptors and the more suitable half‐life of fluorine‐18, MDL 100907 was radiofluorinated in four steps using 1‐(2‐bromoethyl)‐4‐[¹⁸F]fluorobenzene as a secondary labelling precursor. The complex reaction required an overall reaction time of 140 min and (±)‐[¹⁸F]MDL 100907 was obtained with a specific activity of at least 30 GBq/µmol (EOS) and an overall radiochemical yield of 1–2%. In order to verify its binding to 5‐HT_2A receptors, in vitro rat brain autoradiography was conducted showing the typical distribution of 5‐HT_2A receptors and a very low non‐specific binding of about 6% in frontal cortex, using ketanserin or spiperone for blocking. Thus, [¹⁸F]MDL 100907 appears to be a promising new 5‐HT_2A PET ligand. Copyright © 2008 John Wiley & Sons, Ltd.     

Synthesis,labelling and first evaluation of [18F]R91150 as a serotonin 5‐HT2A receptor antagonist for PET

In psychiatric disorders such as anxiety, depression and schizophrenia, 5‐HT_2A receptors play an important role. In order to investigate them in vivo there is an increasing interest in selective and high‐affinity radioligands for receptor binding studies using positron emission tomography (PET). Since available radioligands have disadvantages, R91150, which is a selective and high‐affinity ligand for 5‐HT_2A receptors, was labelled with fluorine‐18. This was accomplished in six steps via 4‐[¹⁸F]fluorophenol and 1‐(3‐bromopropoxy)‐4‐[¹⁸F]fluorobenzene within 190 min starting from no‐carrier‐added [¹⁸F]fluoride. The overall radiochemical yield was 3.8±2% and the specific activity was at least 335 GBq/µmol at the end of the synthesis. First ex vivo studies in mice proved the uptake of [¹⁸F]R91150 in the brain. Radiometabolite studies revealed no radiometabolites in the brain, whereas in the plasma at least two could be detected 30 min p.i. Further preclinical studies are encouraged to evaluate the potential of this new 5‐HT_2A ligand as a radiotracer for PET. Copyright © 2008 John Wiley & Sons, Ltd.     

Evaluation of [18F]2FP3 in pigs and non‐human primates

So far, no suitable 5‐HT₇R radioligand exists for clinical positron emission tomography (PET) imaging. [¹⁸F]2FP3 was first tested in vivo in cats, and the results were promising for further evaluations. Here, we evaluate the radioligand in pigs and non‐human primates (NHPs). Furthermore, we investigate species differences in 5‐HT₇R binding with [³H]SB‐269970 autoradiography in post‐mortem pig, NHP, and human brain tissue. Specific binding of [¹⁸F]2FP3 was investigated by intravenous administration of the 5‐HT₇R specific antagonist SB‐269970. [³H]SB‐269970 autoradiography was performed as previously described. [¹⁸F]2FP3 was synthesized in an overall yield of 35% to 45%. High brain uptake of the tracer was found in both pigs and NHPs; however, pretreatment with SB‐269970 only resulted in decreased binding of 20% in the thalamus, a 5‐HT₇R–rich region. Autoradiography on post‐mortem pig, NHP, and human tissues revealed that specific binding of [³H]SB‐269970 was comparable in the thalamus of pig and NHP. Despite the high uptake of [¹⁸F]2FP3 in both species, the binding could only be blocked to a limited degree with the 5‐HT₇R antagonists. We speculate that the affinity of the radioligand is too low for imaging the 5‐HT₇Rs in vivo and that part of the PET signal arises from targets other than the 5‐HT₇R.     

Synthesis of novel WAY 100635 derivatives containing a norbornene group and radiofluorination of [18F]AH1.MZ as a serotonin 5‐HT1A receptor antagonist for molecular imaging

5‐HT_1A receptors are involved in a variety of psychiatric disorders and in vivo molecular imaging of the 5‐HT_1A status represents an important approach to analyze and treat these disorders. We report herein the synthesis of three new fluoroethylated 5‐HT_1A ligands (AH1.MZ, AH2.MZ and AH3.MZ) as arylpiperazine derivatives containing a norbornene group. AH1.MZ (K_i= 4.2 nM) and AH2.MZ (K_i=30 nM) showed reasonable in vitro affinities to the 5‐HT_1A receptor, whereas AH3.MZ appeared to be non‐affine toward the 5‐HT_1A receptor. The receptor profile of AH1.MZ and AH2.MZ showed selectivity within the 5‐HT system. ¹⁸F‐labelling via [¹⁸F]FETos to [¹⁸F]AH1.MZ was carried out in radiochemical yields of >70%. The final formulation of injectable solutions including [¹⁸F]FETos synthon synthesis, radiosynthesis and semi‐preparative high‐performance liquid chromatography (HPLC) separation took no longer than 130 min and provided [¹⁸F]AH1.MZ with a purity of >98% as indicated by analytical HPLC analyses. Copyright © 2009 John Wiley & Sons, Ltd.     

Current radiosynthesis strategies for 5‐HT2A receptor PET tracers

Serotonin 2A receptors have been implicated in various psychophysiological functions and disorders such as depression, Alzheimer's disease, or schizophrenia. Therefore, neuroimaging of this specific receptor is of significant clinical interest, and it is not surprising that many attempts have been made to develop a suitable 5‐HT_2AR positron emission tomography‐tracer. In this review, we give an overview on the precursor, reference compound synthesis, and the preparation of promising 5‐HT_2AR radiopharmaceuticals applied in positron emission tomography. We also highlight possible learning outcomes that can be made from these tracer development processes.     

Development of novel PET probes, [18F]BCPP‐EF, [18F]BCPP‐BF,and [11C]BCPP‐EM for mitochondrial complex 1 imaging in the living brain

We developed three novel positron‐emission tomography (PET) probes, 2‐tert‐butyl‐4‐chloro‐5‐{6‐[2‐(2[¹⁸F]fluoroethoxy)‐ethoxy]‐pyridin‐3‐ylmethoxy}‐2H‐pyridazin‐3‐one ([¹⁸F]BCPP‐EF), 2‐tert‐butyl‐4‐chloro‐5‐[6‐(4‐[¹⁸F]fluorobutoxy)‐pyridin‐3‐ylmethoxy]‐2H‐pyridazin‐3‐one ([¹⁸F]BCPP‐BF), and 2‐tert‐butyl‐4‐chloro‐5‐{6‐[2‐(2‐[¹¹C]methoxy‐ethoxy)‐ethoxy]‐pyridin‐3‐ylmethoxy}‐2H‐pyridazin‐3‐one ([¹¹C]BCPP‐EM), for quantitative imaging of mitochondrial complex 1 (MC‐1) activity in vivo. These three PET probes were successfully labeled by nucleophilic [¹⁸F]fluorination or by [¹¹C]methylation of their corresponding precursor with sufficient radioactivity yield, good radiochemical purity, and sufficiently high specific radioactivity for PET measurement. The specificity of these probes for binding to MC‐1 was assessed with rotenone, a specific MC‐1 inhibitor, by a rat brain slice imaging method in vitro. Rat whole‐body imaging by small‐animal PET demonstrated that all probes showed high uptake levels in the brain as well as in the heart sufficient to image them clearly. The rank order of uptake levels in the brain and the heart just after injection was as follows: high in [¹⁸F]BCPP‐BF, intermediate in [¹¹C]BCPP‐EM, and low in [¹⁸F]BCPP‐EF. The kinetics of [¹⁸F]BCPP‐EF and [¹¹C]BCPP‐EM provided a reversible binding pattern, whereas [¹⁸F]BCPP‐BF showed nonreversible accumulation‐type kinetics in the brain and heart. Metabolite analyses indicated that these three compounds were rapidly metabolized in the plasma but relatively stable in the rat brain up to 60 min post‐injection. The present study demonstrated that [¹⁸F]BCPP‐EF could be a useful PET probe for quantitative imaging of MC‐1 activity in the living brain by PET.     

How to increase the reactivity of [18F]fluoroethyl bromide: [18F]fluoroethylation of amine,phenol and amide functional groups with [18F]FEtBr, [18F]FEtBr/NaI and [18F]FEtOTf

[¹⁸F]Fluoroethyl bromide ([¹⁸F]FEtBr) is a useful synthetic precursor to synthesize ¹⁸F‐labeled compounds. However, the lower reactivity of [¹⁸F]FEtBr with amine, phenol and amide functional groups than that of [¹¹C]CH₃I partly limits its wide application in the synthesis of [¹⁸F]fluoroethylated compounds. The aim of this study was to increase the reactivity of [¹⁸F]FEtBr with various nucleophilic substrates for PET tracers containing amine, phenol and amide moieties. The present strategies included (1) adding NaI into the reaction mixture of [¹⁸F]FEtBr and substrate, where [¹⁸F]FEtI is reversibly formed and becomes more reactive; (2) converting [¹⁸F]FEtBr into much more reactive [¹⁸F]FEtOTf, similar to conversion of [¹¹C]CH₃I into [¹¹C]CH₃OTf. By these efforts, the [¹⁸F]fluoroethylation efficiency of various substrates containing amine, phenol and amide groups with [¹⁸F]FEtBr/NaI and [¹⁸F]FEtOTf was significantly improved, compared with the corresponding reaction efficiency with [¹⁸F]FEtBr. Copyright © 2003 John Wiley & Sons, Ltd.     

Synthesis and evaluation of [O‐methyl‐11C]4‐[3‐[4‐(2‐methoxyphenyl)‐ piperazin‐1‐yl]propoxy]‐4‐aza‐tricyclo[5.2.1.02,6]dec‐8‐ene‐3,5‐dione as a 5‐HT1A receptor agonist PET ligand

4‐[3‐[4‐(2‐Methoxyphenyl)piperazin‐1‐yl]propoxy]‐4‐aza‐tricyclo[5.2.1.02,6]dec‐8‐ene‐3,5‐dione (4), a potent and selective 5‐HT_1A agonist, was labeled by ¹¹C‐methylation of the corresponding desmethyl analogue 3 with ¹¹C‐methyl triflate. The precursor molecule 3 was synthesized from commercially available endo‐N‐hydroxy‐5‐norbornene‐2,3‐dicarboximide in two steps with an overall yield of 40%. Radiosynthesis of ¹¹C‐4 was achieved in 35 min in 20±5% yield (n=6) at the end of synthesis with a specific activity of 2600±250 Ci/mmol. In vivo positron emission tomography (PET) studies in baboon revealed rapid uptake of the tracer into the brain. However, lack of specific binding indicates that ¹¹C‐4 is not useful as a 5‐HT_1A agonist PET ligand for clinical studies. Copyright © 2008 John Wiley & Sons, Ltd.     

Synthesis of [18F]FETO,a novel potential 11‐β hydroxylase inhibitor

Recent publications reported high uptake of the carbon‐11 labelled 11β‐hydroxylase inhibitors (R)–[O–methyl‐¹¹C]metomidate ([¹¹C]MTO) and (R)–[O–ethyl‐¹¹C]etomidate ([¹¹C]ETO) in adrenocortical incidentalomas with excellent selectivity for positron emission tomography (PET). In our studies [¹⁸F]FETO, (the [¹⁸F]fluoroethyl ester of etomidate, (R)‐1‐(1‐phenylethyl)‐1H‐imidazole‐5‐carboxylic acid, 2′‐[¹⁸F]fluoroethyl ester), an analogue of [¹¹C]MTO and [¹¹C]ETO was chosen due to the suspected similarity of the pharmacokinetic and pharmacodynamic properties, and was prepared in the following two step procedure: First, [¹⁸F]fluoride was reacted with 2‐bromoethyl triflate using the kryptofix/acetonitrile method to yield 2–bromo‐[¹⁸F]fluoroethane ([¹⁸F]BFE). In the second step, [¹⁸F]BFE was reacted with the tetrabutylammonium salt of (R)‐1‐(1‐phenylethyl)‐1H‐imidazole‐5‐carboxylic acid to yield [¹⁸F]FETO, a novel inhibitor of the 11β‐hydroxylase. The proposed synthesis of [¹⁸F]FETO allows the production of sufficient amounts of this new PET‐tracer to serve 1–2 patients with an overall synthesis time of less than 80 min. Copyright © 2003 John Wiley & Sons, Ltd.     

Baeyer‐Villiger oxidation tuned to chemoselective conversion of non‐activated [18F]fluorobenzaldehydes to [18F]fluorophenols

A reaction pathway via oxidation of [¹⁸F]fluorobenzaldehydes offers a very useful tool for the no‐carrier‐added radiosynthesis of [¹⁸F]fluorophenols, a structural motive of several potential radiopharmaceuticals. A considerably improved chemoselectivity of the Baeyer‐Villiger oxidation (BVO) towards phenols was achieved, employing 2,2,2‐trifluoroethanol as reaction solvent in combination with Oxone or m‐CPBA as oxidation agent. The studies showed the necessity of H₂SO₄ addition, which appears to have a dual effect, acting as catalyst and desiccant. For example, 2‐[¹⁸F]fluorophenol was obtained with a RCY of 97% under optimised conditions of 80°C and 30‐minute reaction time. The changed performance of the BVO, which is in agreement with known reaction mechanisms via Criegee intermediates, provided the best results with regard to radiochemical yield (RCY) and chemoselectivity, i.e. formation of [¹⁸F]fluorophenols rather than [¹⁸F]fluorobenzoic acids. Thus, after a long history of the BVO, the new modification now allows an almost specific formation of phenols, even from electron‐deficient benzaldehydes. Further, the applicability of the tuned, chemoselective BVO to the n.c.a. level and to more complex compounds was demonstrated for the products n.c.a. 4‐[¹⁸F]fluorophenol (RCY 95%; relating to 4‐[¹⁸F]fluorobenzaldehyde) and 4‐[¹⁸F]fluoro‐m‐tyramine (RCY 32%; relating to [¹⁸F]fluoride), respectively.     

Optimization and synthesis of an 18F‐labeled dopamine D3 receptor ligand using [18F]fluorophenylazocarboxylic tert‐butylester

There is still no efficient fluorine‐18‐labeled dopamine D₃ subtype selective receptor ligand for studies with positron emission tomography. We aim at improving the D₃ selectivity and hydrophilicity of a candidate ligand by changing the substitution pattern to a 2,3‐dichlorophenylpiperazine and hydroxylation of the butyl chain. The compound [¹⁸F]3 exhibited D₃ affinity of K_i = 3.6 nM, increased subtype selectivity (K_i(D₂/D₃) = 60), and low affinity to 5‐HT_1A and α₁ receptors (K_i (5‐HT_1A/D₃) = 34; K_i (α₁/D₃) = 100). The two‐step radiosynthesis was optimized for analog [¹⁸F]4 by reducing the necessary concentration of the precursor amine (57 mM), which reacted with [¹⁸F]fluorophenylazocarboxylic tert‐butylester under basic conditions. The optimization of the base (Cs ₂CO₃, 23 mM) and the adjustment of reaction temperature led to the radiochemical yield of 63% after 5 min at 35°C. The optimized reaction conditions were transferred on to the synthesis of [¹⁸F]3 with an overall non‐decay corrected yield of 8‐12% in a specific activity of 32‐102 GBq/µmol after a total synthesis time of 30‐35 min. This provides a D ₃ radioligand candidate with improved attributes concerning selectivity and radiosynthesis for further preclinical studies.     

Automated one‐step radiosynthesis of the CB1 receptor imaging agent [18F]MK‐9470

The fluorine‐18‐labeled positron emission tomography (PET) radiotracer [¹⁸F]MK‐9470 is a selective, high affinity inverse agonist that has been used to image the cannabinoid receptor type 1 in human brain in healthy and disease states. This report describes a simplified, one‐step [¹⁸F]radiofluorination approach using a GE TRACERlab FX_FN module for the routine production of this tracer. The one‐step synthesis, by [¹⁸F]fluoride displacement of a primary tosylate precursor, gives a six‐fold increase in yield over the previous two‐step method employing O‐alkylation of a phenol precursor with 1,2‐[¹⁸F]fluorobromoethane. The average radiochemical yield of [¹⁸F]MK‐9470 using the one‐step method was 30.3 ± 11.7% (n = 12), with specific activity in excess of 6 Ci/µmol and radiochemical purity of 97.2 ± 1.5% (n = 12), in less than 60 min. This simplified, high yielding, automated process was validated for routine GMP production of [¹⁸F]MK‐9470 for clinical studies.     

No‐carrier added synthesis of 18F‐labelled nucleosides using Stille cross‐coupling reactions with 4‐[18F]fluoroiodobenzene

The radiosyntheses of 5‐(4′‐[¹⁸F]fluorophenyl)‐uridine [¹⁸F]‐11 and 5‐(4′‐[¹⁸F]fluorophenyl)‐2′‐deoxy‐uridine [¹⁸F]‐12 are described. The 5‐(4′‐[¹⁸F]fluoro‐phenyl)‐substituted nucleosides were prepared via a Stille cross‐coupling reaction with 4‐[¹⁸F]fluoroiodobenzene followed by basic hydrolysis using 1 M potassium hy‐droxide. The Stille cross‐coupling reaction was optimized by screening various palladium complexes, additives and solvents. By using optimized labelling conditions (Pd₂(dba)₃/CuI/AsPh₃ in DMF/dioxane (1:1), 20 min at 65°C), 550 MBq of [4‐¹⁸F]fluoroiodobenzene could be converted into 120 MBq (33%, decay‐corrected) of 5‐(4′‐[¹⁸F]fluorophenyl)‐2′‐deoxy‐uridine [¹⁸F]‐12 within 40 min, including HPLC purification. Copyright © 2004 John Wiley & Sons, Ltd.     

Synthesis and preliminary in vivo evaluation of 4‐[18F]fluoro‐N‐{2‐[4‐(6‐trifluoromethylpyridin‐2‐yl)piperazin‐1‐yl]ethyl}benzamide,a potential PET radioligand for the 5‐HT1A receptor

4‐Fluoro‐N‐{2‐[4‐(6‐trifluoromethylpyridin‐2‐yl)piperazin‐1‐yl]ethyl}benzamide is a full 5‐HT_1A agonist with high affinity (pK_i=9.3), selectivity and a c log P of 3.045. The corresponding PET radioligand 4‐[¹⁸F]fluoro‐N‐{2‐[4‐(6‐trifluoromethylpyridin‐2‐yl)piperazin‐1‐yl]ethyl}benzamide was synthesized by nucleophilic aromatic substitution on the nitro precursor. The fluorinating agent K[¹⁸F]F/Kryptofix 2.2.2 was both dried (9 min, 700 W) and incorporated in the precursor (5 min, 700 W) using a commercially available microwave oven. In a total synthesis time of 60 min, an overall radiochemical yield of 18% (SD=5, n=7, EOS) was obtained. Radiochemical purity was always higher than 99% and specific activity always higher than 81.4 GBq/µmol (2.2 Ci/µmol). Initial brain uptake in mice was 2.19% ID (5.47% ID/g, 2 min) but decreased rapidly (0.17% ID, 0.45% ID/g (60 min)). During the first 20 min p.i., radioactivity concentration of the brain was significantly higher than that of blood demonstrating good brain entry of the tracer. Copyright © 2004 John Wiley & Sons, Ltd.     

Synthesis of a phenolic precursor and its efficient O‐[18F]fluoroethylation with purified no‐carrier‐added [18F]2‐fluoroethyl brosylate as the labeling agent

[¹⁸F]2‐Fluoroethyl‐p‐toluenesulfonate also called [¹⁸F]2‐fluoroethyl tosylate has been widely used for labeling radioligands for positron emission tomography (PET). [¹⁸F]2‐Fluoroethyl‐4‐bromobenzenesulfonate, also called [¹⁸F]2‐fluoroethyl brosylate ([¹⁸F]F(CH₂)₂OBs), was used as an alternative radiolabeling agent to prepare [¹⁸F]FEOHOMADAM, a fluoroethoxy derivative of HOMADAM, by O‐fluoroethylating the phenolic precursor. Purified by reverse‐phase HPLC, the no‐carrier‐added [¹⁸F]F(CH₂)₂OBs was obtained in an average radiochemical yield (RCY) of 35%. The reaction of the purified and dried [¹⁸F]F(CH₂)₂OBs with the phenolic precursor was performed by heating in DMF and successfully produced [¹⁸F]FEOHOMADAM, after HPLC purification, in RCY of 21%. Copyright © 2013 John Wiley & Sons, Ltd.     

Fine‐tuning of the automated [18F]PSMA‐1007 radiosynthesis

Radiolabeled prostate‐specific membrane antigen (PSMA) targeting PET‐tracers have become desirable radiopharmaceuticals for the imaging of prostate cancer (PC). Recently, the PET radiotracer [¹⁸F]PSMA‐1007 was introduced as an alternative to [⁶⁸Ga]Ga‐PSMA‐11, for staging and diagnosing biochemically recurrent PC. We incorporated a one‐step procedure for [¹⁸F]PSMA‐1007 radiosynthesis, using both Synthra RNplus and GE TRACERlab FxFN automated modules, in accordance with the recently described radiolabeling procedure. Although the adapted [¹⁸F]PSMA‐1007 synthesis resulted in repeatable radiochemical yields (55 ± 5%, NDC), suboptimal radiochemical purities of 87 ± 8% were obtained using both modules. As described here, modifications made to the radiolabeling and the solid‐phase extraction purification steps reduced synthesis time to 32 minutes and improved radiochemical purity to 96.10%, using both modules, without shearing the radiochemical yield.     

Synthesis of 18F‐labelled biphenyls via SUZUKI cross‐coupling with 4‐[18F]fluoroiodobenzene

The SUZUKI reaction of organoboron compounds with 4‐[¹⁸F]fluoroiodobenzene has been developed as a novel radiolabelling technique in ¹⁸F chemistry. The cross‐coupling reaction of p‐tolylboronic acid with 4‐[¹⁸F]fluoroiodobenzene was used to screen different palladium complexes, bases and solvents. Optimized reaction conditions (Pd₂(dba)₃, Cs₂CO₃, acetonitrile, 60°C for 5 min) were further applied to the synthesis of various ¹⁸F‐labelled biphenyls bearing different functional groups. The reaction proceeded in excellent radiochemical yields of up to 94% within 5 min while showing good compatibility to many functional groups. Copyright © 2006 John Wiley & Sons, Ltd.     

Microfluidic radiosynthesis and biodistribution of [18F] 2‐(5‐fluoro‐pentyl)‐2‐methyl malonic acid

Microfluidics technology has emerged as a powerful tool for the radiosynthesis of positron emission tomography (PET) and single‐photon emission computed tomography radiolabeled compounds. In this work, we have exploited a continuous flow microfluidic system (Advion, Inc., USA) for the [¹⁸F]‐fluorine radiolabeling of the malonic acid derivative, [¹⁸F] 2‐(5‐fluoro‐pentyl)‐2‐methyl malonic acid ([¹⁸F]‐FPMA), also known as [¹⁸F]‐ML‐10, a radiotracer proposed as a potential apoptosis PET imaging agent. The radiosynthesis was developed using a new tosylated precursor. Radiofluorination was initially optimized by manual synthesis and served as a basis to optimize reaction parameters for the microfluidic radiosynthesis. Under optimized conditions, radio‐thin‐layer chromatography analysis showed 79% [¹⁸F]‐fluorine incorporation prior to hydrolysis and purification. Following hydrolysis, the [¹⁸F]‐FPMA was purified by C18 Sep‐Pak, and the final product was analyzed by radio‐HPLC (high‐performance liquid chromatography). This resulted in a decay‐corrected 60% radiochemical yield and ≥98% radiochemical purity. Biodistribution data demonstrated rapid blood clearance with less than 2% of intact [¹⁸F]‐FPMA radioactivity remaining in the circulation 60 min post‐injection. Most organs showed low accumulation of the radiotracer, and radioactivity was predominately cleared through kidneys (95% in 1 h). Radio‐HPLC analysis of plasma and urine samples showed a stable radiotracer at least up to 60 min post‐injection.     

Automated production of [18F]FTHA according to GMP

14‐(R,S)‐[¹⁸F]fluoro‐6‐thia‐heptadecanoic acid is a tracer for fatty acid imaging by positron emission tomography. High demand for this tracer required us to replace semiautomatic synthesis with a fully automated procedure. An automated synthesis device was constructed in‐house for multistep nucleophilic ¹⁸F‐fluorination and a control system was developed. The synthesis device was combined with a sterile filtration unit and both were qualified. 14‐(R,S)‐[¹⁸F]fluoro‐6‐thia‐heptadecanoic acid was produced according to good manufacturing practice guidelines set by the European Union. The synthesis includes an initial nucleophilic labelling reaction, deprotection, preparative HPLC separation, purification of the final product, and formulation for injection. The duration and temperature of the reaction and hydrolysis were optimized, and the radiochemical stability of the formulated product was determined. The rotary evaporator used to evaporate the solvent after HPLC purification was replaced with solid phase extraction purification. We also replaced the human serum albumin used in the earlier procedure with a phosphate buffer‐ascorbic acid mixture in the final formulation solution. From 2011 to 2016, we performed 219 synthesis procedures, 94% of which were successful. The radiochemical yield of 14‐(R,S)‐[¹⁸F]fluoro‐6‐thia‐heptadecanoic acid, decay‐corrected to the end of bombardment, was 13% ± 6.3%. The total amount of formulated end product was 1.7 ± 0.8 GBq at end of synthesis.     

[18F]Fluoride recovery via gaseous [18F]HF

Acidification of target water with H₂SO₄ in a specially constructed glassy carbon/polyethylene apparatus allowed for recovery of up to 82% of [¹⁸F]fluoride as [¹⁸F]HF gas. The [¹⁸F]HF distillate was found to be acid‐free but moist; when passed through a solution of ^tBuPh₂SiOTf, it yielded [¹⁸F]^tBuPh₂SiF. The multivariate design of experiment showed that the key to high yield of [¹⁸F]HF was the efficient degassing of the reaction mixture.