Positron emission tomography (PET) is a molecular imaging technique that employs isotopes such as fluorine-18 (t1/2 = 109.7 min), which are covalently bound to biologically active molecules.  Such molecules are injected in vivo and imaged with a PET scanner for functional activity.  Our laboratory has recently discovered a spirocyclic hypervalent iodine(III) precursor for nucleophilic displacement with [18F]fluoride to prepare non-activated (hetero)aromatics with excellent regioselectivity. The objective of this project was to synthesize an array of spirocyclic labeling precursors with various substituents in order to study electronic and/or steric effects on the corresponding radiofluorination and to further improve the radiochemical yield for incorporation of fluorine-18. More than 15 substrates were prepared by a one-step condensation reaction with malonic acid and various ketone derivatives. The product was then coupled with 4-diacetoxyiodobiphenyl (a model substrate) in the presence of 10% Na2CO3(aq.) in EtOH to afford the ensuing precursor for radiolabeling with over 40% overall yield. A preliminary evaluation of the efficiency of these scaffolds in the radiofluorination was carried out with [18F]Et4NF in DMF at 120 �C for 10 min. The incorporation yield and identity of the molecule were determined by radioTLC and radioHPLC respectively (n = 3). We have identified several lead compounds which provided more than 50% incorporation yields and further improvement is underway to improve on the thermostability of the precursor as well as test the method on a wide scope of well-functionalized molecules.  Further radiolabeling of these hypervalent iodiine(III) based precursors is underway and will also be presented.

Synthesis of ylide-based precursors for reactions with [<sup>18</sup>F]fluoride towards positron emission tomography (PET) radiopharmaceuticals

248th National Meeting (2014)

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Synthesis of ylide-based precursors for reactions with [18F]fluoride towards positron emission tomography (PET) radiopharmaceuticals

Synthesis of ylide-based precursors for reactions with [¹⁸F]fluoride towards positron emission tomography (PET) radiopharmaceuticals