Pre-clinical validation of orthotopically-implanted pulmonary tumor by imaging with 18F-fluorothymidine-positron emission tomography/computed tomography.
The development of positron-emission tomography (PET) and X-ray computed tomography (CT) imaging has improved the detection of tumor burden and, in turn, pre-clinical drug development and clinical treatment. In pre-clinical drug development, clinically-relevant murine cancer models, such as orthotopic models of lung cancer, have provided an accurate representation of tumor burden in humans. However, evidence demonstrating the capability of imaging-guided evaluation of these clinically-relevant models is limited. Here, we combined (18)F-fluorothymidine (FLT)-PET/CT imaging and a murine model of human non-small cell lung cancer (NSCLC) to improve the accuracy of anticancer drug evaluation in pre-clinical studies. We found that FLT-PET/CT imaging enabled the progression of pulmonary tumors to be longitudinally monitored rather than FDG-PET/CT. Furthermore, in an efficacy study of a standard treatment of docetaxel in a murine lung cancer model, FLT-PET imaging detected the anticancer response earlier than volumetric analysis by CT imaging. We, thus, observed a relationship between the alteration of FLT signals and Ki-67 index in the pulmonary tumor during the period of chemotherapy. These results indicate that the combination of FLT-PET/CT imaging and an orthotopic NSCLC model is an effective strategy for evaluating clinical efficacy and potential of an anticancer agent during pre-clinical development.
Astellas Pharma Inc., 21 Miyukigaoka, Tsukuba, Ibaraki, 305-8585 Japan. hiroshi.fushiki@astellas.com.
Hiroshi
H
Fushiki
Sosuke
S
Miyoshi
Akihiro
A
Noda
Yoshihiro
Y
Murakami
Hiroshi
H
Sasaki
Makoto
M
Jitsuoka
Keisuke
K
Mitsuoka
Ichiro
I
Matsunari
Shintaro
S
Nishimura
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D002289:Carcinoma, Non-Small-Cell Lung / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D015224:Dideoxynucleosides; D000077143:Docetaxel; D004353:Drug Evaluation, Preclinical; D019788:Fluorodeoxyglucose F18; D006801:Humans; D008175:Lung Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000473:pathology; D008297:Male; D051379:Mice; D008819:Mice, Nude; D064847:Multimodal Imaging; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals; D043823:Taxoids / Q000494:pharmacology; D014057:Tomography, X-Ray Computed; D047368:Tumor Burden; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D015224:Dideoxynucleosides; D019275:Radiopharmaceuticals; D043823:Taxoids; D019788:Fluorodeoxyglucose F18; D000077143:Docetaxel
FLT-PET/CT; orthotopic lung cancer model