Assessment of tumor cell proliferation using [F-18]fluorodeoxyadenosine and [F-18]fluoroethyluracil

被引:13
作者
Kim, CG
Yang, DJ
Kim, EE
Cherif, A
Kuang, LR
Li, C
Tansey, W
Liu, CW
Li, SC
Wallace, S
Podoloff, DA
机构
[1] UNIV TEXAS, MD ANDERSON CANC CTR, DEPT NUCL MED, HOUSTON, TX 77030 USA
[2] UNIV TEXAS, MD ANDERSON CANC CTR, DEPT LAB MED, HOUSTON, TX 77030 USA
关键词
D O I
10.1021/js950402i
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
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 ([F-18]FEU) was prepared by treating 2,4-dimethoxy-5-(2-hydroxyethyl)pyrimidine with (KF)-F-18, followed by hydrolysis with HBr. Fluorodeoxyadenosine ([F-18]FAD) was prepared by treating a triacetylated analogue of adenosine with (KF)-F-18. In vitro cell proliferation assay of [F-18]- 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 [F-18]FEU incorporated into DNA/RNA during cell proliferation. Tumor-to-tissue count density ratios of [F-18]FAD and [F-18]. FEU increased as a function of time. [F-18]FAD had higher tumor-to-nontumor tissue count density ratios than [F-18]FEU. Autoradiograms of [F-18]FEU and [F-18]FAD, and PET images of [F-18]FEU, showed that the tumors could be well visualized. The results suggest that [F-18]FEU and [F-18]FAD have potential use in evaluating tumor cell proliferation by PET.
引用
收藏
页码:339 / 344
页数:6
相关论文
共 33 条
  • [1] STUDIES ON F-18-LABELED PYRIMIDINES - TUMOR UPTAKES OF 5-FLUOROURACIL-F-18, 5-FLUOROURIDINE-F-18, AND 5-FLUORODEOXYURIDINE-F-18 IN ANIMALS
    ABE, Y
    FUKUDA, H
    ISHIWATA, K
    YOSHIOKA, S
    YAMADA, K
    ENDO, S
    KUBOTA, K
    SATO, T
    MATSUZAWA, T
    TAKAHASHI, T
    IDO, T
    [J]. EUROPEAN JOURNAL OF NUCLEAR MEDICINE, 1983, 8 (06): : 258 - 261
  • [2] CHU CK, 1989, CHEM PHARM BULL, V37, P336
  • [3] GOETHALS P, 1995, J NUCL MED, V36, P880
  • [4] 2'-FLUORINATED ARABINONUCLEOSIDES OF 5-(2-HALOALKYL)URACIL - SYNTHESIS AND ANTIVIRAL ACTIVITY
    GRIENGL, H
    WANEK, E
    SCHWARZ, W
    STREICHER, W
    ROSENWIRTH, B
    DECLERCQ, E
    [J]. JOURNAL OF MEDICINAL CHEMISTRY, 1987, 30 (07) : 1199 - 1204
  • [5] HIGASHI K, 1993, J NUCL MED, V34, P414
  • [6] NUCLEOSIDES .158. FLUORINATED SUGAR ANALOGS OF POTENTIAL ANTI-HIV-1 NUCLEOSIDES
    HUANG, JT
    CHEN, LC
    WANG, L
    KIM, MH
    WARSHAW, JA
    ARMSTRONG, D
    ZHU, QY
    CHOU, TC
    WATANABE, KA
    MATULICADAMIC, J
    SU, TL
    FOX, JJ
    POLSKY, B
    BARON, PA
    GOLD, JWM
    HARDY, WD
    ZUCKERMAN, E
    [J]. JOURNAL OF MEDICINAL CHEMISTRY, 1991, 34 (05) : 1640 - 1646
  • [7] IKEHARA M, 1978, CHEM PHARM BULL, V26, P2449
  • [8] CONFORMATIONAL RIGIDITY OF SPECIFIC PYRIMIDINE RESIDUES IN TRANSFER-RNA ARISES FROM POSTTRANSCRIPTIONAL MODIFICATIONS THAT ENHANCE STERIC INTERACTION BETWEEN THE BASE AND THE 2'-HYDROXYL GROUP
    KAWAI, G
    YAMAMOTO, Y
    KAMIMURA, T
    MASEGI, T
    SEKINE, M
    HATA, T
    IIMORI, T
    WATANABE, T
    MIYAZAWA, T
    YOKOYAMA, S
    [J]. BIOCHEMISTRY, 1992, 31 (04) : 1040 - 1046
  • [9] CELL CYCLE-DEPENDENT REGULATION OF P185(NEU) - A RELATIONSHIP BETWEEN DISRUPTION OF THIS REGULATION AND TRANSFORMATION
    KIYOKAWA, N
    YAN, DH
    BROWN, ME
    HUNG, MC
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1995, 92 (04) : 1092 - 1096
  • [10] KUBOTA K, 1991, J NUCL MED, V32, P2118