Synthesis of 3′‐deoxy‐3′‐[18F]fluoro‐1‐β‐D‐xylofuranosyluracil ([18F]‐FMXU) for PET

The synthesis of a pyrimidine analog, 3′‐deoxy‐3′‐[¹⁸F]‐fluoro‐1‐β‐D ‐xylofuranosyluracil ([¹⁸F]‐FMXU) is reported. 5‐Methyluridine 1 was converted to its di‐methoxytrityl derivatives 2 and 3 as a mixture. After separation the 2′,5′‐di‐methoxytrityluridine 2 was converted to its 3′‐triflate 4 followed by derivatization to the respective N³‐t‐Boc product 5 . The triflate 5 was reacted with tetrabutylammonium[¹⁸F]fluoride to produce 6 , which by acid hydrolysis yielded compound 7 . The crude preparation was purified by HPLC to obtain the desired product [¹⁸F]‐FMXU. The radiochemical yields were 25–40% decay corrected (d. c.) with an average of 33% in four runs. Radiochemical purity was >99% and specific activity was >74 GBq/µmol at the end of synthesis (EOS). The synthesis time was 67–75 min from the end of bombardment (EOB). Copyright © 2005 John Wiley & Sons, Ltd.     

Synthesis of [18F]‐labeled N‐3(substituted) thymidine analogues: N‐3([18F]fluorobutyl) thymidine ([18F]‐FBT) and N‐3([18F]fluoropentyl) thymidine ([18F]‐FPT) for PET

Syntheses of N‐3(substituted) analogues of thymidine, N‐3([¹⁸F]fluorobutyl)thymidine ([¹⁸F]‐FBT) and N‐3([¹⁸F]fluoropentyl)thymidine ([¹⁸F]‐FPT) are reported. 1,4‐Butane diol and 1,5 pentane diol were converted to their tosyl derivatives 2 and 3 followed by conversion to benzoate esters 4 and 5, respectively. Protected thymidine 1 was coupled separately with 4 and 5 to produce 6 and 7 , which were hydrolyzed to 8 and 9 , then converted to their mesylates 10 and 11 , respectively. Compounds 10 and 11 were fluorinated with n‐Bu₄N[¹⁸F] to produce 12 and 13 , which by acid hydrolysis yielded 14 and 15 , respectively. The crude products were purified by HPLC to obtain [¹⁸F]‐FBT and [¹⁸F]‐FPT. The radiochemical yields were 58–65% decay corrected (d.c.) for 14 and 46–57% (d.c.) for 15 with an average of 56% in three runs per compound. Radiochemical purity was >99% and specific activity was >74 GBq/µmol at the end of synthesis (EOS). The synthesis time was 65–75 min from the end of bombardment (EOB). Copyright © 2006 John Wiley & Sons, Ltd.     

A fully automated synthesis of [18F]‐FEAU and [18F]‐FMAU using a novel dual reactor radiosynthesis module

2′‐Deoxy‐2′‐[¹⁸F]fluoro‐5‐substituted‐1‐β‐D ‐arabinofuranosyluracils, including 2′‐deoxy‐2′‐[¹⁸F]fluoro‐5‐methyl‐1‐β‐D ‐arabinofuranosyluracil [¹⁸F]FMAU and [¹⁸F]FEAU are established radiolabeled probes to monitor cellular proliferation and herpes simplex virus type 1 thymidine kinase (HSV1‐tk) reporter gene expression with positron emission tomography. For clinical applications, a fully automated CGMP‐compliant radiosynthesis is necessary for production of these probes. However, due to multiple steps in the synthesis, no such automated synthetic protocols have been developed. We report here a fully automated synthesis of [¹⁸F]‐FEAU and [¹⁸F]‐FMAU on a prototype dual reactor module TRACERlab FX FN. The synthesis was performed by using a computer‐programmed standard operating procedure, and the product was purified on a semipreparative high‐performance liquid chromatography (HPLC) integrated with the synthesis module using 12% EtOH in 50 mM Na₂HPO₄. Finally, the percentage of alcohol was adjusted to 7% by adding Na₂HPO₄ and filtered through a Millipore filter to make dose for human. The radiochemical yield on the fluorination was 40±10% (n=10), and the overall yields were 4±1% (d. c.), from the end of the bombardment; [¹⁸F]FEAU (n=7) and [¹⁸F]FMAU (n=3). The radiochemical purity was >99%, specific activity was 1200–1300 mCi/µmol. The synthesis time was 2.5 h. This automated synthesis should be suitable for production of [¹⁸F]FIAU, [¹⁸F]FFAU, [¹⁸F]FCAU, [¹⁸F]FBAU and other 5‐substitued thymidine analogues. Copyright © 2009 John Wiley & Sons, Ltd.     

Synthesis of [18F]‐labeled 2′‐deoxy‐2′‐fluoro‐5‐methyl‐1‐β‐D‐arabinofuranosyluracil ([18F]‐FMAU)

Synthesis of 2′‐deoxy‐2′‐[¹⁸F]fluoro‐5‐methyl‐1‐β‐D‐arabinofuranosyluracil ([¹⁸F]‐FMAU) is reported. 2‐Deoxy‐2‐[¹⁸F]fluoro‐1,3,5‐tri‐O‐benzoyl‐α‐D‐arabinofuranose 2 was prepared by the reaction of the respective triflate 1 with tetrabutylammonium[¹⁸F]fluoride. The fluorosugar 2 was converted to its 1‐bromo‐derivative 3 and coupled with protected thymine 4 . The crude product mixture ( 5a and 5b ) was hydrolyzed in base and purified by HPLC to obtain the radiolabeled FMAU 6a . The radiochemical yield of 6a was 20–30% decay corrected (d.c.) in four steps with an average of 25% in four runs. Radiochemical purity was >99% and average specific activity was 2300 mCi/μmol at the end of synthesis (EOS). The synthesis time was 3.5–4.0 h from the end of bombardment (EOB). Copyright © 2002 John Wiley & Sons, Ltd.     

Radiosynthesis of 6‐([18F]fluoroacetamido)‐1‐hexanoicanilide ([18F]FAHA) for PET imaging of histone deacetylase (HDAC)

Radiosynthesis of a novel substrate for histone deacetylase (HDAC), 6‐([¹⁸F]fluoroacetamido)‐1‐hexanoicanilide ([¹⁸F]FAHA, [¹⁸F]‐ 3 ) is reported. For precursor synthesis, compound 1 (6‐amino‐1‐hexanoicanilide) was prepared by the reaction of 6‐amino hexanoic acid with thionyl chloride in dichloroethane followed by addition of aniline. Compound 1 was reacted with bromoacetic anhydride in tetrahydrofuran (THF) in the presence of triethylamine to produce the precursor compound 6‐(bromoacetamido)‐1‐hexanoicanilide 2 . Fluorination reactions were performed using tetrabutylammonium fluoride in various solvents at 80°C to prepare the unlabeled reference compound 3 . Radiofluorinations were performed using either n‐Bu₄N¹⁸F or K¹⁸F/kryptofix, and the crude product was purified by high performance liquid chromatography (HPLC). The radiochemical yields were 9–13% decay corrected (d.c.) with an average of 11% using K¹⁸F/kryptofix, and specific activity >2 GBq/µmol at the end of synthesis. The synthesis time was 67–75 min from the end of bombardment (EOB). Copyright © 2006 John Wiley & Sons, Ltd.     

Synthesis and quality control of [18F]T807 for tau PET imaging

The detailed synthesis and quality control of [¹⁸F]T807, radiotracer for tau protein aggregate imaging, are described. The radiotracer synthesis was accomplished in an average of 48 min with an average specific activity at end‐of‐synthesis of over 4.4 TBq/µmole (120 Ci/µmole) and an average radiochemical yield of 32%. Compliance with all standard US Pharmacopeia Chapter <823> acceptance tests was observed.     

Radiosynthesis of [18F]ATPFU: a potential PET ligand for mTOR

Mammalian target of rapamycin (mTOR) plays a pivotal role in many aspects of cellular proliferation, and recent evidence suggests that an altered mTOR signaling pathway plays a central role in the pathogenesis of aging, tumor progression, neuropsychiatric, and major depressive disorder. Availability of a mTOR‐specific PET tracer will facilitate monitoring early response to treatment with mTOR inhibitors that are under clinical development. Towards this we have developed the radiosynthesis of [¹⁸F]1‐(4‐(4‐(8‐oxa‐3‐azabicyclo[3.2.1]octan‐3‐yl)‐1‐(2,2,2‐trifluoroethyl)‐1H‐pyrazolo[3,4‐d]pyrimidin‐6‐yl)phenyl)‐3‐(2‐fluoroethyl)urea [¹⁸F]ATPFU ([¹⁸F]1) as an mTOR PET ligand. Synthesis of reference 1 and the precursor for radiolabeling, 4‐(4‐8‐oxa‐3‐azabicyclo[3.2.1]‐octan‐3yl)‐1‐(2,2,2‐trifluoroethyl)‐1H‐pyrazolo[3,4‐d]pyrimidin‐6yl)aniline (10), were achieved from beta‐chloroaldehyde 3 in 4 and 5 steps, respectively, with an overall yield of 25–28%. [¹⁸F]Fluoroethylamine was prepared by heating N‐[2‐(toluene‐4‐sulfonyloxy)ethyl]phthalimide with [¹⁸F]fluoride ion in acetonitrile. [¹⁸F]1 was obtained by slow distillation under argon of [¹⁸F]FCH₂CH₂NH₂ into amine 10 that was pre‐treated with triphosgene at 0–5 °C. The total time required for the two‐step radiosynthesis including semi‐preparative HPLC purification was 90 min, and the overall radiochemical yield of [¹⁸F]1 for the process was 15 ± 5% based on [¹⁸F]fluoride ion (decay corrected). At the end of synthesis (EOS), the specific activity was 37–74 GBq/µmol (N = 6).     

N3‐Substituted thymidine analogues III: radiosynthesis of N3‐[(4‐[18F]fluoromethyl‐phenyl)butyl]thymidine ([18F]‐FMPBT) and N3‐[(4‐[18F]fluoromethyl‐phenyl)pentyl] thymidine ([18F]‐FMPPT) for PET

Radiosyntheses of two N³‐substituted thymidine analogues, N³‐[(4[¹⁸F]fluoromethyl‐phenyl)butyl]thymidine ([¹⁸F]‐FMPBT) and N³‐[(4[¹⁸F]fluoromethyl‐phenyl)pentyl]thymidine ([¹⁸F]‐FMPPT), are reported. The precursor compounds 9 and 10 were synthesized in six steps and the standard compounds 13 and 14 were synthesized from these precursors. For radiosynthesis, compounds 9 and 10 were fluorinated with n‐Bu₄N[¹⁸F] to produce [¹⁸F]‐ 11 and [¹⁸F]‐ 12 , which by acid hydrolysis yielded [¹⁸F]‐ 13 and [¹⁸F]‐ 14 , respectively. The crude products were purified by high‐performance liquid chromatography to obtain [¹⁸F]‐FMPBT and [¹⁸F]‐FMPPT. The average decay‐corrected radiochemical yield for [¹⁸F]‐ 13 was 15% in five runs, and that for [¹⁸F]‐ 14 was 10% in four runs. The radiochemical purity was >99% and the specific activity was >74 GBq/µmol at the end of synthesis. The synthesis time was 80–90 min from the end of bombardment. Copyright © 2007 John Wiley & Sons, Ltd.     

A general synthesis of 2′‐deoxy‐2′‐[18F]fluoro‐1‐β‐D‐arabinofuranosyluracil and its 5‐substituted nucleosides

Several 2′‐deoxy‐2′‐[¹⁸F]fluoro‐1‐β‐D‐arabinofuranosyluracil derivatives have been synthesized. Coupling of 1‐bromo‐2‐deoxy‐2‐[¹⁸F]fluoro‐3,5‐di‐O‐benzoyl‐α‐D‐arabinofuranose 2 with protected uracil derivatives 3a–e followed by hydrolysis and high‐performance liquid chromatography purification produced the radiolabeled nucleosides 4a–e in 15–30% yield (d. c.), >99% radiochemical purity and 55.5–103.6 GBq/µmol specific activities. Copyright © 2003 John Wiley & Sons, Ltd.     

Synthesis of 2‐[(2‐chloro‐2′‐[18F]fluoroethyl)amino]‐2H‐1,3,2‐oxazaphosphorinane‐2‐oxide (18F‐fluorocyclophosphamide), a potential tracer for breast tumor prognostic imaging with PET

A fluorine‐18 labeled analog of the widely used chemotherapeutic agent cyclophosphamide was synthesized as a tracer for prognostic imaging with positron emission tomography. 2‐[(2‐Chloro‐2′‐[¹⁸F]fluoroethyl)amino]‐2H‐1,3,2‐oxazaphosphorinane‐2‐oxide (¹⁸F‐fluorocyclophosphamide), was prepared by direct halogen exchange reaction from the parent cyclophosphamide. In small‐scale syntheses, radiochemical yields of up to 4.9% and specific activities of 960 Ci/mmol were achieved in a total synthesis time of 60–75 min. The [¹⁸F]‐labeled cyclophosphamide analog with radioactive purity >99% and chemical purity >96% was suitable for in vivo (microPET imaging) and ex vivo studies of a murine model of human breast tumors. Copyright © 2005 John Wiley & Sons, Ltd.     

Synthesis of 6‐acrylamido‐4‐(2‐[18F]fluoroanilino)quinazoline: a prospective irreversible EGFR binding probe

Acrylamido‐quinazolines substituted at the 6‐position bind irreversibly to the intracellular ATP binding domain of the epidermal growth factor receptor (EGFR). A general route was developed for preparing 6‐substituted‐4‐anilinoquinazolines from [¹⁸F]fluoroanilines for evaluation as EGFR targeting agents with PET. By a cyclization reaction, 2‐[¹⁸F]fluoroaniline was reacted with N′‐(2‐cyano‐4‐nitrophenyl)‐N,N‐dimethylimidoformamide to produce 6‐nitro‐4‐(2‐[¹⁸F]fluoroanilino)quinazoline in 27.5% decay‐corrected radiochemical yield. Acid mediated tin chloride reduction of the nitro group was achieved in 5 min (80% conversion) and subsequent acylation with acrylic acid gave 6‐acrylamido‐4‐(2‐[¹⁸F]fluoroanilino)quinazoline in 8.5% decay‐corrected radiochemical yield, from starting fluoride, in less than 2 h. Copyright © 2005 John Wiley & Sons, Ltd.     

Copper‐mediated reduction of 2‐[18F]fluoroethyl azide to 2‐[18F]fluoroethylamine

¹⁸F‐labelled fluoroalkylamines are attractive reagents for the preparation of positron emission tomography tracers containing amine, amide, and N‐heterocyclic moieties. Herein, we report that 2‐[¹⁸F]fluoroethylamine can be obtained from 2‐[¹⁸F]fluoroethyl azide by reduction with elemental copper under acidic conditions. Azide to amine reduction was achieved in near quantitative analytical yields within 30 min by heating a solution of 2‐[¹⁸F]fluoroethyl azide in the presence of copper wire and aqueous trifluoroacetic acid. Subsequent reaction of 2‐[¹⁸F]fluoroethylamine with benzoyl chloride in the presence of triethylamine provided N‐[¹⁸F]fluoroethyl benzamide in 63% decay‐corrected radiochemical yield from 2‐[¹⁸F]fluoroethyl azide. The utility of the Cu(0)/H⁺ azide reduction method was further exemplified by preparation of the potential GABA_A tracer 9H‐β‐carboline N‐2‐[¹⁸F]fluoroethylamide, which was obtained in 46% decay‐corrected radiochemical yield by reaction of 2‐[¹⁸F]fluoroethylamine with the corresponding 9H‐β‐carboline pentafluorophenyl ester. Copyright © 2012 John Wiley & Sons, Ltd.     

Synthesis of 18F‐labeled cyclooxygenase‐2 (COX‐2) inhibitor as a potential PET imaging agent

A new PET tracer for COX‐2 imaging, the 6‐ethoxy‐3‐(4‐methanesulfonylphenyl)‐4‐(4‐[¹⁸F]fluorophenyl)pyran‐2‐one ([¹⁸F]EFMP), was synthesized. For F‐18 radiolabeling, a trimethylammonium precursor and a brominated precursor were synthesized from 1,1,2,3‐tetrachlorocycloprop‐2‐ene in 6 steps. The radiolabeling was achieved through nucleophilic substitution using no‐carrier‐added (n.c.a.) fluorine‐18. Solid‐phase extraction and semi‐preparative‐HPLC purification produced [¹⁸F]EFMP in 14.6±3.3% (n =4) decay corrected radiochemical yield with a specific activity of 487±85.1 (n =4) Ci/mmol and greater than 98% radiochemical purity. Copyright © 2006 John Wiley & Sons, Ltd.     

Two‐step radiosynthesis of [18F]N‐succinimidyl‐4‐fluorobenzoate ([18F]SFB)

The acylation reagent [¹⁸F]N‐succinimidyl‐4‐fluorobenzoate (¹⁸F‐SFB) has been prepared using a new two‐step approach. The starting material p‐[¹⁸F]fluorobenzaldehyde (¹⁸F‐FBA) was obtained by an improved radiosynthesis with a decay‐corrected radiochemical yield of 66±6 % (n=3). Reaction of ¹⁸F‐FBA with (diacetoxyiodine)benzene and N‐hydroxysuccinimide and preparative HPLC purification furnished ¹⁸F‐SFB in an r.c.y. of 49±6 % (n=3), based on the starting radioactivity of ¹⁸F‐FBA. The radiochemical purity of ¹⁸F‐SFB was >99%. Alternatively, purification by solid phase extraction gave ¹⁸F‐SFB with an r.c.y. of 77±9% (n=4) and a radiochemical purity of 89±5% (n=4). This radiochemical synthesis only used non‐aqueous solvents, which simplifies the method and facilitates subsequent applications of ¹⁸F‐SFB. Copyright © 2009 John Wiley & Sons, Ltd.     

Novel synthesis of [18F]‐fluorobenzene and pyridinecarbohydrazide‐folates as potential PET radiopharmaceuticals

In an attempt to visualize folate receptors that over‐express on many cancers, [¹⁸F]‐fluorobenzene and pyridine carbohydrazide‐folates were synthesized using two different synthetic approaches starting from nucleophilic displacement reactions on ethyl‐trimethylammonium‐benzoate and pyridine carboxylate precursors. The intermediates ethyl [¹⁸F]‐fluorinated benzene and pyridine esters were reacted with hydrazine to produce the [¹⁸F]‐fluorobenzene and pyridine carbohydrazides followed by coupling with NHS‐folate 11 in the first approach. Whereas hydrazide‐folate 5 was reacted with 2,5‐dioxoazolidinyl [¹⁸F]‐fluorobenzenecarboxylate in the second approach. Based on starting [¹⁸F]‐fluoride, radiochemical yields and synthesis times were found to be around 80% (45 min) and 35% (80 min) for the first and the second approaches, respectively. The first synthetic approach holds considerable promise as a rapid and simple method for the radiofluorination of folic acid with high radiochemical yield and short time. Copyright © 2005 John Wiley & Sons, Ltd.     

Synthesis of [18F]Fluoroclofilium as a potential cardiac imaging agent for PET studies

N‐4‐(4‐chlorophenyl)butyl‐N,N‐diethyl‐7‐[¹⁸F]fluoroheptylammonium ([¹⁸F]‐fluoroclofilium) has been prepared as a potential cardiac imaging agent. For the synthesis of this radiolabelled ammonium salt, its tosyloxylated analogue was prepared as a precursor, and the non‐radioactive fluorine analogue was synthesized as a reference compound. Radiofluorination was achieved by the treatment of N‐4‐(4‐chlorophenyl)butyl‐N,N‐diethyl‐7‐(p‐toluenesulfonyloxy)heptylammonium p‐toluenesulfonate with ¹⁸F^? in the presence of Kryptofix‐2.2.2 in acetonitrile. Copyright © 2003 John Wiley & Sons, Ltd.     

Photoconjugation of 3‐azido‐5‐nitrobenzyl‐[18F]fluoride to an oligonucleotide aptamer

Photoconjugation techniques are well established in biochemistry and molecular biology applications. We report here the first application of photoconjugation to label an oligonucleotide with positron emitting fluorine‐18. ANBF, 3‐azido‐5‐nitrobenzyl fluoride, was tagged with fluorine‐18 in 30–50% yield from the corresponding tosylate. The HPLC purified [¹⁸F]ANBF was photochemically conjugated to a hexylamine modified 15‐base, single stranded, DNA aptamer with up to 20% radiolabeling efficiency, based on starting [¹⁸F]ANBF. Separation by gel exclusion chromatography and HPLC analysis of the DNA fractions indicated that the benzyl fluoride was covalently bound to the aptamer. The total reaction time from the start of radiosynthesis was 135 min. Based on these results, the feasibility to photolabel oligonucleotide molecules with fluorine‐18 labeled arylazides for PET applications has been established. Copyright © 2002 John Wiley & Sons, Ltd.     

Modified PEG‐anilinoquinazoline derivatives as potential EGFR PET agents

Inhibition of epidermal growth factor receptor tyrosine kinase (EGFR‐TK) has emerged as a major approach for cancer‐targeted therapy. Consequently, there has been a great interest in the use of labeled EGFR‐TK inhibitors as positron emission tomography (PET) imaging agents. Currently, the developed agents did not yield adequate PET imaging of animal models probably due to poor solubility, rapid washout from blood, and low stability in vivo. In order to overcome these hurdles, new derivatives of previously reported inhibitors (ML04, 2) with decreased log P and increased solubility were designed and synthesized. These compounds (3–5) exhibited high autophosphorylation inhibitory potency with an IC₅₀ of 5–35 nM, decreased log P's (3.1, 3.34, and 3.45, respectively), and significantly increased solubility (630, 300, and 120 µg/mL, respectively) relative to the previously reported parent compound 2 (log P=3.7, solubility=3.5 µg/mL). The labeling of compound 5 with [¹⁸F] and compounds 3 and 4 with [¹¹C] and [¹²⁴I], respectively, involved a one‐step radiosynthesis. Compounds 3–5 were obtained with a total decay‐corrected radiochemical yields of 13, 31, and 5%, respectively, and were found to be stable in blood. The positive outcome achieved with compounds 3–5 merits further in vivo evaluation as PET bioprobes. Copyright © 2008 John Wiley & Sons, Ltd.     

Radiosynthesis of 1′‐[18F]fluoroethyl‐β‐D‐lactose ([18F]‐FEL) for early detection of pancreatic carcinomas with PET

Introduction: The hepatocellular carcinoma–intestine–pancreas and pancreatitis‐associated proteins, also known as lactose‐binding protein, is upregulated in peritumoral pancreatic tissue. Previously, we reported ethyl‐ β ‐D ‐galactopyranosyl‐(1,4′)‐2′‐deoxy‐2′‐[¹⁸F]fluoro‐ β ‐D ‐glucopyranoside (Et‐[¹⁸F]‐FDL), a radiofluorinated lactose analog for positron emission tomography (PET) of small pancreatic carcinomas in mice. However, synthesis of the precursor for Et‐[¹⁸F]‐FDL involves 11 steps, which is quite lengthy, and produces overall low yields. Here, we report on synthesis and radiolabeling of another analog of lactose, the 1′‐[¹⁸F]fluoroethyl‐ β ‐D ‐lactose for PET imaging of pancreatic carcinomas. Methods: Two precursor compounds, 1′‐bromoethyl‐2′,3′,6′,2,3,4,6‐hepta‐O‐acetyl‐ β ‐D ‐lactose 4, and 1′‐p‐toluenesulfonylethyl‐2′,3′,6′,2,3,4,6‐hepta‐O‐acetyl‐ β ‐D ‐lactose 5, were synthesized in two and three steps, respectively; then, cold fluorination and radiofluorination of these precursors were performed. The reaction mixture was passed through a silica gel Sep‐pack cartridge, eluted with EtOAc, and the 1′‐[¹⁸F]fluoroethyl‐2′,3′,6′,2,3,4,6‐hepta‐O‐acetyl‐ β ‐D ‐lactose ([¹⁸F]‐6) purified by HPLC. After hydrolysis of the protecting groups, the 1′‐[¹⁸F]fluoroethyl‐ β ‐D ‐lactose [¹⁸F]‐7 was neutralized, diluted with saline, filtered through a sterile Millipore filter, and analyzed by radio‐TLC. Results: The average decay‐corrected radiochemical yield was 9% (n = 7) with>99% radiochemical purity and specific activity of 55.5 GBq/ µ mol. Conclusion : A new analog of lactose, 1′‐[¹⁸F]fluoroethyl‐ β ‐D ‐lactose, has been synthesized in good yields, with high purity and high specific activity suitable for PET imaging of early pancreatic carcinomas. Copyright © 2011 John Wiley & Sons, Ltd.     

Efficient methods for the synthesis of 5‐(4‐[18F]fluorophenyl)‐10,15,20‐tris(3‐methoxyphenyl)porphyrin as a potential imaging agent for tumor

F‐18‐labeled porphyrins, the potential tracing and detecting agents for tumor have been synthesized and characterized by two convenient routes: one is a mixed aldehyde condensation, which involves acid‐catalyzed condensation of pyrrole, m‐anisaldehyde and 4‐[¹⁸F]fluorobenzaldehyde. The other is the acid‐catalyzed condensation of tetrapyrrane with 4‐[¹⁸F]fluorobenzaldehyde. The synthetic methodologies including solvents, reaction concentrations and catalysts are optimized for radiolabeled porphyrins. The methods also provide the desired product in reasonable radiochemical yield (20–26%) compared with those of cold chemical synthesis (1–3%) and with high radiochemical purity (>95%). The methods described here would be effective and convenient ways to produce radiolabeled porphyrin. Copyright © 2005 John Wiley & Sons, Ltd.