DCE-MRI of the hypoxic fraction, radioresponsiveness, and metastatic propensity of cervical carcinoma xenografts.
OBJECTIVE
Locoregional treatment failure and poor survival rates are associated with extensive hypoxia in the primary tumor in advanced cervical carcinoma. The potential of gadolinium diethylene-triamine penta-acetic acid (Gd-DTPA)-based dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in assessing the hypoxic fraction, radioresponsiveness, and metastatic propensity of cervical carcinomas was investigated in this preclinical study.


METHODS
CK-160 and TS-415 cervical carcinoma xenografts were used as tumor models. DCE-MRI was carried out at 1.5 T, and parametric images of K(trans) and v(e) were produced by pharmacokinetic analysis of the DCE-MRI series. Pimonidazole was used as a hypoxia marker. Tumor radioresponsiveness was determined by irradiating tumors with five fractions of 4 Gy in 48 h and measuring cell survival in vitro. Metastatic propensity was determined by examining host mice for tumor growth in lymph nodes.


RESULTS
Low values of K(trans) were associated with extensive hypoxia and radiation resistance in tumors of both lines and with high incidence of metastases in CK-160 tumors. Associations between ve and hypoxia, radioresponsiveness, or metastatic propensity were not found in any of the tumor lines.


CONCLUSIONS
K(trans) is a potentially useful biomarker of tumor hypoxia, radiation resistance, and metastatic growth in advanced cervical carcinoma.
Department of Radiation Biology, Institute for Cancer Research, Oslo University Hospital, Norway.
Christine
C
Ellingsen
Department of Radiation Biology, Institute for Cancer Research, Oslo University Hospital, Norway.
Tord
T
Hompland
Department of Radiation Biology, Institute for Cancer Research, Oslo University Hospital, Norway.
Kanthi
K
Galappathi
Department of Radiation Biology, Institute for Cancer Research, Oslo University Hospital, Norway.
Berit
B
Mathiesen
Department of Radiation Biology, Institute for Cancer Research, Oslo University Hospital, Norway. Electronic address: einar.k.rofstad@rr-research.no.
Einar K
EK
Rofstad
D000818:Animals; D015687:Cell Hypoxia / Q000502:physiology; D002470:Cell Survival / Q000502:physiology; D003287:Contrast Media; D005260:Female; D019786:Gadolinium DTPA; D006801:Humans; D008207:Lymphatic Metastasis; D008279:Magnetic Resonance Imaging / Q000379:methods; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009593:Nitroimidazoles / Q000494:pharmacology; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology; D011877:Radionuclide Imaging; D002583:Uterine Cervical Neoplasms / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology / Q000532:radiotherapy*; D023041:Xenograft Model Antitumor Assays
D003287:Contrast Media; D009593:Nitroimidazoles; D011838:Radiation-Sensitizing Agents; C033815:pimonidazole; D019786:Gadolinium DTPA
Cervical carcinoma xenografts; DCE-MRI; Hypoxia; Metastasis; Radioresponsiveness