NON INVASIVE MEASUREMENT OF THYMIDYLATE SYNTHASE INHIBIT

U Of L Imperial Col Of Sci/Technlgy/Med, London

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Abstract

DESCRIPTION: (Applicant's Description) Thymidylate synthase (TS) is the target of several anticancer agents due its important role in the de novo synthesis of DNA. There is the need to evaluate TS inhibition in tissues in order to assess objectively the efficacy of TS inhibitors. This proposal focuses on the development and application of in vivo Positron Emission Tomography (PET) to evaluate TS inhibition noninvasively in tumours and normal tissues of patients undergoing treatment. This involves quantitative measurement of the fractional retention of carbon-11 labelled thymidine in tissues using PET. Comparisons will be made with direct measurement of TS inhibition in biopsy specimen of the imaged tumour and also by measurement of plasma deoxyuridine levels. As proof of principle, we aim to evaluate the effect of the TS inhibitor 5-fluorouracil alone and in combination with folinic acid on 64 patients who will be entered into the study. This study will consolidate and facilitate the development of more efficacious TS inhibitors.