Changes in tumor hypoxia induced by mild temperature hyperthermia as assessed by dual-tracer immunohistochemistry.
OBJECTIVE
To study the changes in hypoxia resulting from mild temperature hyperthermia (MTH) in a subcutaneous xenograft model using dual-tracer immunohistochemical techniques.


METHODS
HT29 tumors were locally heated at 41 degrees C. Changes in tumor hypoxia were investigated by pimonidazole and EF5. Pimonidazole was given 1h preheating, EF5 at various times during or after treatment, 1h later the animals were sacrificed. Blood vessels were identified by CD31 staining, and perfusion by Hoechst 33342 injected 1 min pre-sacrifice.


RESULTS
The overall hypoxic fraction was significantly decreased by MTH during and immediately after heating. However, MTH induced both increases and decreases in tumor hypoxia in different parts of the tumor. Specifically, MTH decreased hypoxia in the regions with relatively well-perfused blood vessels, but increased hypoxia in regions that were poorly perfused. At 24-h post heating, newly formed hypoxic regions surrounded previously-hypoxic foci, which in turn surrounded pimonidazole-stained debris. Quantitative analysis did not evince changes in tumor oxygenation due to MTH at 24h post-treatment.


CONCLUSIONS
In this xenograft model, the effect of MTH on tumor oxygenation was variable, both spatially and kinetically. Overall tumor oxygenation was improved during and after heating, but the effect was short-lived.
Sun
Xiaorong
X
Department of Medical Physics, Memorial Sloan-Kettering Cancer Center, NY 10065, USA.
Li
Xiao-Feng
XF
Russell
James
J
Xing
Ligang
L
Urano
Muneyasu
M
Li
Gloria C
GC
Humm
John L
JL
Ling
C Clifton
CC
D000230:Adenocarcinoma / Q000098:blood supply / Q000378:metabolism*; D000704:Analysis of Variance; D000818:Animals; D015687:Cell Hypoxia; D015179:Colorectal Neoplasms / Q000098:blood supply / Q000378:metabolism*; D017341:Etanidazole / Q000031:analogs & derivatives / Q000494:pharmacology; D005260:Female; D006845:Hydrocarbons, Fluorinated / Q000494:pharmacology; D006979:Hyperthermia, Induced; D007150:Immunohistochemistry / Q000379:methods*; D051379:Mice; D009593:Nitroimidazoles / Q000494:pharmacology; D010100:Oxygen / Q000378:metabolism*; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D014183:Transplantation, Heterologous; D005466:Fluorocarbons
D017341:Etanidazole; D006845:Hydrocarbons, Fluorinated; D009593:Nitroimidazoles; D010100:Oxygen; D011838:Radiation-Sensitizing Agents; C096011:2-(2-nitro-1H-imidazol-1-yl)-N-(2,2,3,3,3-pentafluoropropyl)acetamide; D005466:Fluorocarbons; C033815:pimonidazole