Reference - Detail
|Author||Tsuji AB, Sogawa C, Sugyo A, Sudo H, Toyohara J, Koizumi M, Abe M, Hino O, Harada YN, Furukawa T, Suzuki K, Saga T.|
|Title||Comparison of conventional and novel PET tracers for imaging mesothelioma in nude mice with subcutaneous and intrapleural xenografts.|
|Journal||Nucl. Med. Biol.|
INTRODUCTION:Malignant mesothelioma is a highly aggressive tumor originating in the pleura, peritoneum and pericardium, and the prognosis of patients undergoing current treatment remains poor. To develop new therapies, it is important to have a noninvasive imaging system for evaluating the efficacy of such prospective treatments. We have established clinically relevant mouse models and evaluated conventional and novel positron emission tomography (PET) tracers.
METHODS:Epithelioid and sarcomatoid mesothelioma cells were inoculated subcutaneously and intrapleurally into nude mice. Biodistribution and PET imaging studies were conducted by injecting [(18)F]fluoro-2-deoxy-D-glucose (FDG), 3'-[(18)F]fluoro-3'-doxythymidine (FLT) or 4'-methyl-[(11)C]thiothymidine (S-dThd) into the mouse models. In vitro cellular uptake of [(14)C]FDG and [(3)H]FLT and thymidine kinase 1 (TK(1)) activity in both cell lines were measured. Expression of glucose transporter 1 (GLUT-1) and Ki-67 in xenografted tumors was evaluated by immunohistochemical staining.
RESULTS:In epithelioid mesothelioma models, biodistribution experiments showed that tumor uptake of [(11)C]S-dThd was significantly higher than that of [(18)F]FDG. On the other hand, in sarcomatoid models, [(18)F]FDG showed significantly higher accumulation than the other two tracers. These differential uptakes of the three tracers were confirmed by PET imaging. The cellular uptake of [(14)C]FDG and [(3)H]FLT and TK(1) activity in sarcomatoid cells were higher than those of epithelioid cells. GLUT-1 protein was strongly expressed in sarcomatoid but not in epithelioid tumor. We observed a high percentage of Ki-67-positive cells in both epithelioid and sarcomatoid tumors.
CONCLUSIONS:We established nude mouse models of epithelioid and sarcomatoid subtypes of mesothelioma. PET tracers applicable for the evaluation of epithelioid and sarcomatoid mesothelioma would vary: [(18)F]FLT and [(11)C]S-dThd seemed suitable for the epithelioid subtype and [(18)F]FDG seemed suitable for the sarcomatoid subtype in our mouse models. Our results indicated that cellular uptake and TK(1) activity in vitro are not always consistent with tracer uptake of [(18)F]FLT and [(11)C]S-dThd in vivo. These mouse models and PET imaging might be useful tools for evaluating new and effective treatments in mesothelioma.
|MeSH||Animals Cell Line, Tumor GPI-Linked Proteins Gene Expression Regulation, Neoplastic Glucose Transporter Type 1 / immunology Humans Injections, Subcutaneous Ki-67 Antigen / immunology Male Membrane Glycoproteins / metabolism Mesothelioma / diagnostic imaging* Mesothelioma / genetics Mesothelioma / pathology Mesothelioma / surgery Mice Mice, Nude Pleural Cavity Positron-Emission Tomography / methods* Radioactive Tracers Transplantation, Heterologous|
|WOS Category||RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING|
|Human and Animal Cells|