Synthesis of 2-[18F]fluoroadenosine (2-[18F]FAD) as potential radiotracer for studying malignancies by PET

Abstract

18 F]FAD), a potential radioligand for assessment of adenylate metabolism, was synthesized by carrier-added and no-carrier-added procedures via nucleophilic radiofluorination of 2-fluoroadenosine and 2-iodoadenosine. The radiochemical yield, specific radioactivity and radiochemical purity of carrier-added and no-carrier-added 2-[ 18 F]FAD were 5%, 22-30 mCi/mmol and 99%, and 0.5%, 1200-1700 mCi/mmol and 99%, respectively.

18F-Labeling of Arenes and Heteroarenes for Applications in Positron Emission Tomography

“…258 The synthesis of 2-[ 18 F]fluoroadenosine, from the corresponding iodo and fluoro precursors, under identical conditions gives 5% RCY (carrier-added) and <1% RCY, respectively. 259 A subsequent publication by Barréand co-workers uses a fully benzoyl protected precursor and a nitro leaving group. The use of [ 18 Diaryliodonium salts are air-and moisture-stable compounds first synthesized in 1894.…”

“… Nucleophilic displacement of a chloride leaving group gives access to both 6-[ 18 F]­fluoro-9-benzylpurine and 2-[ 18 F]­fluoro-9-benzylpurine with the use of fluorinating agent [ 18 F]­AgF with carrier added AgF . The synthesis of 2-[ 18 F]­fluoroadenosine, from the corresponding iodo and fluoro precursors, under identical conditions gives 5% RCY (carrier-added) and <1% RCY, respectively . A subsequent publication by Barré and co-workers uses a fully benzoyl protected precursor and a nitro leaving group.…”

Radiochemistry

“…136 Other recently labelled compounds using nucleophilic aromatic substitution have included O-(2-fluoroethyl)-L-tyrosine, 137,138 and N-(3-fluoro-4-nitronaphthyl)-cis-5-norbornene-endo-2,3-dicarboxylic imide. 139 Derivatives of many different amine bases that participate in biochemical processes have also been labelled with fluorine-18, such thymidine, 140,141 guanine, 142 adenosine 143 and pyrimidine. 144 Most labelling is carried out to facilitate imaging in nuclear medicine.…”

Efficient Radiosynthesis of 2-[18F]Fluoroadenosine: A New Route to 2-[18F]Fluoropurine Nucleosides

“…7 The 6-position was efficiently labeled with [ 18 F]F -via substitution of the trimethylammonium salt on various substrates, 8,9 while for the 2-position radiolabeling was reported only in low yield (5% yield with low specific radioactivity). 10,11 Introduction of a fluorine atom at the 2-position on the purine ring often results in beneficial effects from metabolic stability due to enzymatic resistance, especially toward adenosine deaminase, and therefore has a longer in vivo lifetime. 12,13 Thus, an efficient and direct [ 18 F] labeling of purine at the 2-position might provide access to highly valuable tools for PET imaging.…”

“…11,14,15 Moreover, when considering the radiochemistry of [ 18 F]-6, only limited methods have been so far described: The Schiemann reaction widely used for the classical fluorination of purines 16 was proven to be inapplicable to radiochemistry, and the conventional methods using substitution of iodine or fluorine by [ 18 F]KF or [ 18 F]AgF were of low efficiency (low yields and low specific radioactivities were obtained). 10,11 Our strategy to introduce a fluorine-18 atom is illustrated in Figure 1. This approach is based on the use of a nitro group at the 2-position of purines to activate the purine ring and to act as a leaving group for the [ 18 F] nucleophilic aromatic substitution.…”