Evaluation of D-18F-FMT, 18F-FDG, L-11C-MET, and 18F-FLT for monitoring the response of tumors to radiotherapy in mice.
O-18F-fluoromethyl-D-tyrosine (D-18F-FMT) is a promising novel agent for tumor imaging by PET. The aim of this study was to evaluate the potential of D-18F-FMT and the other conventional ligands used for tumor imaging, namely, 18F-FDG, L-11C-methionine (L-11C-MET), and 3'-deoxy-3'-18F-fluorothymidine (18F-FLT), as a PET ligand for monitoring early responses to radiotherapy in tumor-bearing mice.


METHODS
C3H/HeN mice inoculated with murine squamous cell carcinomas were treated with a single dose of x-ray irradiation at 2, 6, 20, or 60 Gy. Tumor uptake of each ligand was examined 1, 3, and 7 d after the irradiation.


RESULTS
Tumor uptake of D-18F-FMT was decreased on day 1 after irradiation at 6, 20, or 60 Gy, and the decrease persisted until day 7. Tumor uptake of 18F-FDG was elevated on days 1 and 3 after irradiation at 2, 6, or 20 Gy, followed by a decrease in uptake on day 7 in mice irradiated at 20 or 60 Gy. Decreased tumor uptake of L-11C-MET was observed only on day 3 after the irradiation. Decreased tumor uptake of 18F-FLT was detected on day 1 after irradiation at 2, 6, 20, or 60 Gy; thereafter, the dose-dependent decrease in uptake was no longer seen. Only for D-18F-FMT were significant positive correlations found between ligand uptake at all the time points examined and tumor volume on day 14 after various doses of irradiation.


CONCLUSIONS
The findings suggest that D-18F-FMT is a promising PET ligand for early-phase detection and prediction of the effects of radiation therapy.
Murayama
Chieko
C
Department of Clinical Pharmacology, Tokai University School of Medicine, Isehara, Kanagawa, Japan. patra@is.icc.u-tokai.ac.jp
Harada
Norihiro
N
Kakiuchi
Takeharu
T
Fukumoto
Dai
D
Kamijo
Akemi
A
Kawaguchi
Akira T
AT
Tsukada
Hideo
H
D000818:Animals; D002250:Carbon Radioisotopes / Q000493:pharmacokinetics; D002294:Carcinoma, Squamous Cell / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy; D045744:Cell Line, Tumor; D015224:Dideoxynucleosides / Q000493:pharmacokinetics; D005260:Female; D005462:Fluorine Radioisotopes / Q000493:pharmacokinetics; D019788:Fluorodeoxyglucose F18 / Q000493:pharmacokinetics; D008715:Methionine / Q000493:pharmacokinetics; D051379:Mice; D008809:Mice, Inbred C3H; D009374:Neoplasms, Experimental / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy*; D049268:Positron-Emission Tomography / Q000379:methods*; D014443:Tyrosine / Q000031:analogs & derivatives / Q000493:pharmacokinetics
D002250:Carbon Radioisotopes; D015224:Dideoxynucleosides; D005462:Fluorine Radioisotopes; C493093:O-(18F)fluoromethyl-L-tyrosine; D019788:Fluorodeoxyglucose F18; D014443:Tyrosine; D008715:Methionine; C002854:alovudine