title: Assessment of tumor cell proliferation using [18F]fluorodeoxyadenosine and[18F]fluoroethyluracil.
abstract: This study was to develop radiofluorinated ethyluracil (FEU) and deoxyadenosine analogues (FAD) for noninvasive assessment of tumor proliferative potential by positron emission tomography (PET). 5-(2-Fluoroethyl)uracil ([18F]FEU) was prepared by treating 2,4-dimethoxy-5-(2-hydroxyethyl)pyrimidine with K18F, followed by hydrolysis with HBr. Fluorodeoxyadenosine ([18F]FAD) was prepared by treating a triacetylated analogue of adenosine with K18F. In vitro cell proliferation assay of [18F]-FEU was performed using human peripheral blood mononucleus cells. Tissue distributions were studied in breast tumor-bearing rats at 0.5, 1, 2 and 4 h along with autoradiography at 45 min postinjection. PET imaging studies were conducted in VX-2 tumor-bearing rabbits. In vitro assay indicated that [18F]FEU incorporated into DNA/RNA during cell proliferation. Tumor-to-tissue count density ratios of [18F]FAD and [18F]-FEU increased as a function of time. [18F]FAD had higher tumor-to-nontumor tissue count density ratios than [18F]FEU. Autoradiograms of [18F]FEU and [18F]FAD, and PET images of [18F]FEU, showed that the tumors could be well visualized. The results suggest that [18F]FEU and [18F]FAD have potential use in evaluating tumor cell proliferation by PET.
authors.affiliation: Department of Nuclear Medicine, University of Texas M. D. Anderson Cancer Center, Houston 77030, USA.
authors.forename: C G
authors.initials: CG
authors.lastname: Kim
authors.forename: D J
authors.initials: DJ
authors.lastname: Yang
authors.forename: E E
authors.initials: EE
authors.lastname: Kim
authors.forename: A
authors.initials: A
authors.lastname: Cherif
authors.forename: L R
authors.initials: LR
authors.lastname: Kuang
authors.forename: C
authors.initials: C
authors.lastname: Li
authors.forename: W
authors.initials: W
authors.lastname: Tansey
authors.forename: C W
authors.initials: CW
authors.lastname: Liu
authors.forename: S C
authors.initials: SC
authors.lastname: Li
authors.forename: S
authors.initials: S
authors.lastname: Wallace
authors.forename: D A
authors.initials: DA
authors.lastname: Podoloff
mesh_terms: D000818:Animals; D001345:Autoradiography; D001943:Breast Neoplasms / Q000378:metabolism*; D002455:Cell Division; D002478:Cells, Cultured; D003839:Deoxyadenosines / Q000378:metabolism*; D005260:Female; D006801:Humans; D011817:Rabbits; D051381:Rats; D014055:Tomography, Emission-Computed; D014498:Uracil / Q000378:metabolism*
chemical_list: D003839:Deoxyadenosines; D014498:Uracil