Control of tumor growth has been reported for several human tumor xenograft models and for a few clinical trials using radioactivity delivered to tumors by linking a radioactive element to an antibody that accumulates in tumor and is retained in tumor tissue for many days, thereby delivering a continuous low dose of radiation in a cancer treatment called Radioimmunotherapy (RAIT). There is a need to understand the effects of RAIT on tumor physiology in order to improve results and to determine why some tumors fail to be controlled by the therapy. The radio-antibodies localize in the tumor near the blood vessels and possibly cause changes in vascular function that may influence intratumoral pH and pO2 and intratumoral interstitial pressure. The net effect of these changes may not only impact on the accumulation of additional doses of radioantibody in a multiple cycle scheme, but may also influence the uptake of other anti-tumor agents (e.g. drugs, or biological response modifiers). In this study we are investigating the effects of low-dose rate radiation on tumor pO2. Low pO2 could mean a tumor is less sensitive to radiation and also potentially less accessible to drug therapy due to a damaged blood supply. Methods to intervene could then result in a more appropriate therapy for individual tumors. Electron paramagnetic resonance (EPR) oximetry with solid paramagnetic materials implanted in the tumor will be used to monitor pO2 over the long term delivery of radiation to determine whether the tumor oxygenation changes during this new form of radiation therapy. Animals to be studied are Nude mice (T-cell deficient) bearing one of six different human tumor xenografts grown s.c on the flank including GW-39, LS174T, HT-29 and GS-7 human colonic carcinomas or ME-180 human cervical carcinoma or the CALU- 3 non-small cell lung adenocarcinoma. Tumors will be implanted with paramagnetic material, 400 um piece of gloxy at one site, or 25 microliters of a slurry of sterile paramagnetic material. After implantation of this material, pO2 will be monitored in the tumor using EPR. Twenty four hours after the first pO2 measurement, mice will be injected with radioactive I-131-intact IgG (~100-200microliters) i.p. I-131 is a radionuclide that deposits its energy within a 1-mm range. Then pO2 will be monitored daily for the first 72 hrs and at about 7 day intervals after that for the duration of the experiment.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Biotechnology Resource Grants (P41)
Project #
5P41RR011602-05
Application #
6353175
Study Section
Project Start
2000-09-01
Project End
2002-04-30
Budget Start
1998-10-01
Budget End
1999-09-30
Support Year
5
Fiscal Year
2000
Total Cost
$12,155
Indirect Cost
Name
Dartmouth College
Department
Type
DUNS #
041027822
City
Hanover
State
NH
Country
United States
Zip Code
03755
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