Animal PET for thioacetamide-induced rat cholangiocarcinoma: a novel and reliable platform.
OBJECTIVE
Cholangiocarcinoma (CCA) is a lethal disease afflicting many thousands of patients worldwide. We have previously developed an oral thioacetamide (TAA)-induced model of rat CCA that recapitulates the histologic progression of human CCA. Our objective was to evaluate the feasibility of animal PET in detecting CCA in the setting of the TAA rat model.


METHODS
Male Sprague-Dawley rats (n = 30) were used in this study. Drinking water with TAA 300 mg/l was administered orally in 26 rats, and animal PET was performed at 20 weeks after initiation of TAA. A total of four rats served as controls. Animal PET images were acquired sequentially using both C-11 acetate and 2-deoxy-2-[F-18]fluoro-D-glucose (FDG) to determine the optimal tracer. Dynamic animal PET images were collected to assess the optimal scan time based on the highest tumor-to-liver (T/L) ratio using time-activity curves. Animal PET findings were compared lesion by lesion with the results of autoradiography and the histological data.


RESULTS
FDG animal PET images had a higher T/L ratio compared to images obtained with C-11 acetate as a marker. The optimal scan time for FDG animal PET was determined as 90 min postinjection of the tracer. This was when the T/L ratio reached its peak. Necropsy and histology confirmed the presence of TAA-induced CCA in 22 rats (84.6 %). Static animal PET images showed intense FDG uptake in 17 of the 22 tumor-bearing animals (77.3%). The average T/L ratio was 1.60 +/- 0.09. The sensitivity and specificity of animal PET in the detection of CCA were 77% (17/22) and 100% (4/4), respectively.


CONCLUSIONS
We conclude that animal PET in the setting of the TAA rat model seems to be feasible for the detection of CCA. Future translational studies are needed to confirm and expand our findings.
Yeh
Chun-Nan
CN
Department of Surgery, Chang Gung Memorial Hospital, Chang Gung University, 5, Fu-Hsing Street, Kwei-Shan, Taoyuan, Taiwan.
Lin
Kun-Ju
KJ
Hsiao
Ing-Tsung
IT
Yen
Tzu-Chen
TC
Chen
Tsung-Wen
TW
Jan
Yi-Yin
YY
Chung
Yi-Hsiu
YH
Lin
Chung-Fu
CF
Chen
Miin-Fu
MF
D000085:Acetates; D000818:Animals; D001345:Autoradiography; D001650:Bile Duct Neoplasms / Q000139:chemically induced* / Q000473:pathology; D001653:Bile Ducts, Intrahepatic / Q000473:pathology; D002250:Carbon Radioisotopes; D002273:Carcinogens / Q000633:toxicity*; D018281:Cholangiocarcinoma / Q000139:chemically induced* / Q000473:pathology; D004195:Disease Models, Animal; D018450:Disease Progression; D005240:Feasibility Studies; D019788:Fluorodeoxyglucose F18 / Q000493:pharmacokinetics; D008297:Male; D049268:Positron-Emission Tomography / Q000379:methods / Q000662:veterinary*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012680:Sensitivity and Specificity; D013853:Thioacetamide / Q000633:toxicity*; D013997:Time Factors
D000085:Acetates; D002250:Carbon Radioisotopes; D002273:Carcinogens; D013853:Thioacetamide; D019788:Fluorodeoxyglucose F18