J. Cancer Mol. 2: 37-43, 2006
[Research Paper]
In Vivo
Evaluation of Combination Use of Two
Radiosensitizers Iododeoxyuridine and Misonidazole: A
Biodistribution Study with Whole-Body Autoradiography
Jeng-Jong Hwang, Hsin-Ell Wang, Hsin-Yu Fang, Fu-Du Chen, and Frank
Q. H. Ngo
Department of Medical Radiation Technology and Institute of
Radiological Sciences, National Yang-Ming University, Taipei, Taiwan
Abstract:
AIM:
To investigate the intratumoral localization and biodistribution of
the combination administration of two radiosensitizers,
iododeoxyuridine
and misonidazole, in the mouse model to evaluate the availability
and possible schedule for future clinical application.
METHODS:
Gamma-scintillation counting and whole-body autoradiography were
adopted to investigate the biodistribution of [131I]iododeoxyuridine
([131I]IUdR)
and [18F]misonidazole
([18F]FMISO)
in KHT sarcoma-bearing C3H/HeN mice.
RESULTS:
The amounts of
[131I]IUdR
incorporated into the DNA of KHT sarcoma cells at 0.5, 2, 4, and
24-h postinjection with single dose were 3.76, 3.50, 3.41, and 3.29
mBq/cell, respectively. The tumor/brain ratios of
[131I]IUdR
calculated from the % injected dose per gram tissue were 14.5, 13.0,
11.5, and 88.0, respectively, at 0.5, 2, 4, and 24 h after
[131I]IUdR
injection; the tumor/blood ratios were 0.76, 0.76, 0.70, and 12.57;
while the tumor/muscle ratios were 3.22, 3.71, 2.56, and 22.00,
respectively. On the other hand, the tumor/brain ratios of
[18F]FMISO
were 1.29, 1.21, 1.26, and 2.48 at 0.5, 1, 2, and 4 h after [18F]FMISO
injection, respectively; while the tumor/muscle ratios were 1.41,
1.30, 1.25, and 2.21. The tumor/muscle ratios were 4.0, 2.0, and
4.7 for
[131I]IUdR
alone,
[131I]IUdR
and
[18F]FMISO
simultaneously for 4 h, and
[131I]IUdR 2 h followed by [18F]FMISO
for another 2 h, respectively. The whole-body
autoradiography
showed uptake of [131I]IUdR
at
the
peripheral region of tumor
while
[18F]FMISO
at the deeper sites.
CONCLUSION:
[131I]IUdR was accumulated at the superficial area while
[18F]FMISO at the deeper hypoxic site of tumor.
Combination use of both radiosensitizers, [131I]IUdR
first 2 h followed by [18F]FMISO
for another 2 h, may be
optimal
to enhance the radiosensitization during radiotherapy.
Keywords:
biodistribution; whole-body autoradiography;
radiosensitizer; [131I]IUdR; [18F]FMISO
Received
9/7/05; Revised 12/8/05; Accepted 12/12/05.
1Correspondence:
Dr. Jeng-Jong Hwang, Institute of Radiological Sciences, National
Yang-Ming University, 155 Li-Nong Street Sec. 2, Taipei 112, Taiwan.
Phone: 886-2-28267064. Fax: 886-2-28201095. Email: jjhwang@ym.edu.tw
2Abbreviations:
IUdR, iododeoxyuridine; MISO, misonidazole; WBAR, whole-body
autoradiography; [18F]FMISO, [18F]misonida-zole;
%ID/g, % injected dose per gram tissue. |
