Use of 3'-deoxy-3'-[18F]fluorothymidine PET to monitor early responses to radiation therapy in murine SCCVII tumors.
OBJECTIVE
3'-Deoxy-3'-[(18)F]fluorothymidine (FLT) is a promising new radiopharmaceutical for imaging cell proliferation. We evaluated whether FLT PET can be used to monitor early responses to radiation treatment.


METHODS
C3H/HeN mice bearing murine squamous cell carcinomas were randomized to irradiation with 0, 10, or 20 Gy. Twenty-four hours later, the mice were sacrificed for histopathological and biological assessment such as cell cycle analysis, Hoechst staining, and clonogenic cell survival assay. PET scans were performed on other mice after injection of [(18)F]FLT or [(18)F]fluorodeoxyglucose (FDG) before and after radiation treatment, and tumor growth was assessed over 9 days.


RESULTS
Histopathological examination detected no morphological changes 24 h after radiation treatment, but cell cycle analysis showed that irradiated tumors had a decreased fraction of cells in S phase and an increased fraction in G2-M phase, compared with nonirradiated tumors. Irradiated tumors also had a higher incidence of apoptotic features and reduced clonogenic cell survival. Tumor growth was significantly delayed in irradiated mice (p<0.001) compared with control mice. PET images showed increased tumoral uptake of both FLT and FDG before radiation treatment. Following irradiation, FLT uptake differed significantly (p=0.020) from that in control mice. In contrast, FDG uptake after irradiation did not differ significantly from that in control mice.


CONCLUSIONS
Our finding that tumor uptake of FLT was reduced at 24 h after radiation treatment suggests that FLT PET may be a promising imaging modality for monitoring the early effects of radiation therapy.
Yang
You-Jung
YJ
Department of Nuclear Medicine, University of Ulsan College of Medicine, Asan Medical Center, 388-1 Pungnap-2dong Songpa-gu, Seoul 138-736, South Korea.
Ryu
Jin-Sook
JS
Kim
Seog-Young
SY
Oh
Seung Jun
SJ
Im
Ki Chun
KC
Lee
Heuiran
H
Lee
Sang-Wook
SW
Cho
Kyung Ja
KJ
Cheon
Gi-Jeong
GJ
Moon
Dae Hyuk
DH
D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000000981:diagnostic imaging* / Q000532:radiotherapy*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015224:Dideoxynucleosides; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D049268:Positron-Emission Tomography / Q000379:methods*; D011379:Prognosis; D019275:Radiopharmaceuticals; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D016896:Treatment Outcome
D015224:Dideoxynucleosides; D019275:Radiopharmaceuticals; C002854:alovudine