The radiation response of cells from 9L gliosarcoma tumours is correlated with [F18]-EF5 uptake.
OBJECTIVE
Tumour hypoxia affects cancer biology and therapy-resistance in both animals and humans. The purpose of this study was to determine whether EF5 ([2-(2-nitro-1-H-imidazol-1-yl)-N-(2,2,3,3,3-pentafluoropropyl)-acetamide]) binding and/or radioactive drug uptake correlated with single-dose radiation response in 9L gliosarcoma tumours.


METHODS
Twenty-two 9L tumours were grown in male Fischer rats. Rats were administered low specific activity (18)F-EF5 and their tumours irradiated and assessed for cell survival and hypoxia. Hypoxia assays included EF5 binding measured by antibodies against bound-drug adducts and gamma counts of (18)F-EF5 tumour uptake compared with uptake by normal muscle and blood. These assays were compared with cellular radiation response (in vivo to in vitro assay). In six cases, uptake of tumour versus muscle was also assayed using images from a PET (positron emission tomography) camera (PENN G-PET).


RESULTS
The intertumoural variation in radiation response of 9L tumour-cells was significantly correlated with uptake of (18)F-labelled EF5 (i.e., including both bound and non-bound drug) using either tumour to muscle or tumour to blood gamma count ratios. In the tumours where imaging was performed, there was a significant correlation between the image analysis and gamma count analysis. Intertumoural variation in cellular radiation response of the same 22 tumours was also correlated with mean flow cytometry signal due to EF5 binding.


CONCLUSIONS
To our knowledge, this is the first animal model/drug combination demonstrating a correlation of radioresponse for tumour-cells from individual tumours with drug metabolism using either immunohistochemical or non-invasive techniques.
Koch
Cameron J
CJ
Departments of Radiation Oncology, University of Pennsylvania, 195 John Morgan Bldg., 37th St & Hamilton Walk, Philadelphia, PA, 19104-6072, USA. kochc@mail.med.upenn.edu
Shuman
Anne L
AL
Jenkins
Walter T
WT
Kachur
Alexander V
AV
Karp
Joel S
JS
Freifelder
Richard
R
Dolbier
William R
WR
Evans
Sydney M
SM
D000818:Animals; D015687:Cell Hypoxia / Q000528:radiation effects; D002470:Cell Survival / Q000528:radiation effects; D019788:Fluorodeoxyglucose F18 / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics; D018316:Gliosarcoma / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000532:radiotherapy*; D008297:Male; D011836:Radiation Tolerance; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics; D051381:Rats; D011916:Rats, Inbred F344
D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18