Synthetic routes to 18F-labelled gemcitabine and related 2’-fluoronucleosides

Meyer, Jan-Philip 2015. Synthetic routes to 18F-labelled gemcitabine and related 2’-fluoronucleosides. PhD Thesis, Cardiff University. Item availability restricted.

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Abstract

Gemcitabine (2’,2’-difluoro-2’-deoxycytidine, dFdC) is an established chemotherapeutic agent used in the treatment of various carcinomas such as lung, breast, bladder and especially pancreatic cancer. However, its general application and bioavailability is compromised due to both poor cell uptake and rapid metabolism by gut and liver cytidine deaminase (CDA). A 18F-gemcitabine positron emission tomography (PET) probe could enable biodistribution studies and the imaging of gemcitabine pharmacodynamics in vivo. However, the potential and clinical relevance of a 18F-gemcitabine PET probe would have to be evaluated using appropriate PET tumour models. In order to approach the synthetic target molecule 18F-dFdC, proof-of-principle studies on more straightforward synthetic targets including 18F-FAU and 18FFAC (see figure below) were carried out first. An appropriate precursor was synthesised for 2’-stereoselective late-stage radiofluorination based on previously developed conditions. First, the 2’-[18F]fluorinated arabino nucleoside 18F-FAU, which was considered as a rapidly accessible 2’-fluorinated uracil-based dFdC analogue was successfully synthesised in our radiochemical laboratory. Subsequently, this procedure was used as a template method to obtain the cytidine analogue 18F-FAC via a novel synthetic route in moderate radiochemical yield (4.3-5.5%, decay-corrected), high specific activity (1700 mCi/μmol) and purity (98%) after a synthesis time of 168 min.

Item Type:	Thesis (PhD)
Date Type:	Completion
Status:	Unpublished
Schools:	Pharmacy
Subjects:	Q Science > Q Science (General)
Uncontrolled Keywords:	Nucleosides; positron emission tomography; radiochemistry; radiopharmaceuticals; fluorination; computational chemistry.
Funders:	Cancer Research Wales, British Association for Cancer Research
Date of First Compliant Deposit:	30 March 2016
Last Modified:	26 Jan 2024 16:26
URI:	https://orca.cardiff.ac.uk/id/eprint/68708

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