Assessment of tumor cell proliferation using [18F]fluorodeoxyadenosine and[18F]fluoroethyluracil.
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.
Kim
C G
CG
Department of Nuclear Medicine, University of Texas M. D. Anderson Cancer Center, Houston 77030, USA.
Yang
D J
DJ
Kim
E E
EE
Cherif
A
A
Kuang
L R
LR
Li
C
C
Tansey
W
W
Liu
C W
CW
Li
S C
SC
Wallace
S
S
Podoloff
D A
DA
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*
D003839:Deoxyadenosines; D014498:Uracil