Early detection of chemoradioresponse in esophageal carcinoma by 3'-deoxy-3'-3H-fluorothymidine using preclinical tumor models.
OBJECTIVE
Early identification of esophageal cancer patients who are responding or resistant to combined chemoradiotherapy may lead to individualized therapeutic approaches and improved clinical outcomes. We assessed the ability of 3'-deoxy-3'-(18)F-fluorothymidine positron emission tomography (FLT-PET) to detect early changes in tumor proliferation after chemoradiotherapy in experimental models of esophageal carcinoma.


METHODS
The in vitro and ex vivo tumor uptake of [(3)H]FLT in SEG-1 human esophageal adenocarcinoma cells were studied at various early time points after docetaxel plus irradiation and validated with conventional assessments of cellular proliferation [thymidine (Thd) and Ki-67] and [(18)F]FLT micro-PET imaging. Imaging-histologic correlation was determined by comparing spatial Ki-67 and [(18)F]FLT distribution in autoradiographs. Comparison with fluorodeoxyglucose (FDG) was done in all experiments.


RESULTS
In vitro [(3)H]FLT and [(3)H]Thd uptake rapidly decreased in SEG-1 cells 24 hours after docetaxel with a maximal reduction of over 5-fold (P = 0.005). The [(3)H]FLT tumor-to-muscle uptake ratio in xenografts declined by 75% compared with baseline (P < 0.005) by 2 days after chemoradiotherapy, despite the lack of change in tumor size. In contrast, the decline of [(3)H]FDG uptake was gradual and less pronounced. Tumor uptake of [(3)H]FLT was more closely correlated with Ki-67 expression (r = 0.89, P < 0.001) than was [(3)H]FDG (r = 0.39, P = 0.08). Micro-PET images depicted similar trends in reduction of [(18)F]FLT and [(18)F]FDG tumor uptake. Autoradiographs displayed spatial correlations between [(18)F]FLT uptake and histologic Ki-67 distribution in preliminary studies.


CONCLUSIONS
FLT-PET is suitable and more specific than FDG-PET for depicting early reductions in tumor proliferation that precede tumor size changes after chemoradiotherapy.
Apisarnthanarax
Smith
S
Department of Radiation Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, 77030, USA.
Alauddin
Mian M
MM
Mourtada
Firas
F
Ariga
Hisanori
H
Raju
Uma
U
Mawlawi
Osama
O
Han
Dongmei
D
Bornmann
William G
WG
Ajani
Jaffer A
JA
Milas
Luka
L
Gelovani
Juri G
JG
Chao
K S Clifford
KS
D000818:Animals; D002453:Cell Cycle / Q000528:radiation effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000528:radiation effects; D003131:Combined Modality Therapy; D015224:Dideoxynucleosides / Q000493:pharmacokinetics; D004938:Esophageal Neoplasms / Q000000981:diagnostic imaging* / Q000473:pathology; D005462:Fluorine Radioisotopes; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D049268:Positron-Emission Tomography / Q000379:methods; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D013329:Structure-Activity Relationship; D014183:Transplantation, Heterologous; D014316:Tritium; D023041:Xenograft Model Antitumor Assays
D015224:Dideoxynucleosides; D005462:Fluorine Radioisotopes; D019275:Radiopharmaceuticals; D014316:Tritium; C002854:alovudine