title: 18FDG, [18F]FLT, [18F]FAZA, and 11C-methionine are suitable tracers for the diagnosis and in vivo follow-up of the efficacy of chemotherapy by miniPET in both multidrug resistant and sensitive human gynecologic tumor xenografts.
abstract: Expression of multidrug pumps including P-glycoprotein (MDR1, ABCB1) in the plasma membrane of tumor cells often results in decreased intracellular accumulation of anticancer drugs causing serious impediment to successful chemotherapy. It has been shown earlier that combined treatment with UIC2 anti-Pgp monoclonal antibody (mAb) and cyclosporine A (CSA) is an effective way of blocking Pgp function. In the present work we investigated the suitability of four PET tumor diagnostic radiotracers including 2-[(18)F]fluoro-2-deoxy-D-glucose ((18)FDG), (11)C-methionine, 3'-deoxy-3'-[(18)F]fluorothymidine ((18)F-FLT), and [(18)F]fluoroazomycin-arabinofuranoside ((18)FAZA) for in vivo follow-up of the efficacy of chemotherapy in both Pgp positive (Pgp(+)) and negative (Pgp(-)) human tumor xenograft pairs raised in CB-17 SCID mice. Pgp(+) and Pgp(-) A2780AD/A2780 human ovarian carcinoma and KB-V1/KB-3-1 human epidermoid adenocarcinoma tumor xenografts were used to study the effect of the treatment with an anticancer drug doxorubicin combined with UIC2 and CSA. The combined treatment resulted in a significant decrease of both the tumor size and the accumulation of the tumor diagnostic tracers in the Pgp(+) tumors. Our results demonstrate that (18)FDG, (18)F-FLT, (18)FAZA, and (11)C-methionine are suitable PET tracers for the diagnosis and in vivo follow-up of the efficacy of tumor chemotherapy in both Pgp(+) and Pgp(-) human tumor xenografts by miniPET.
authors.affiliation: Department of Nuclear Medicine, University of Debrecen, P.O. Box 63, Nagyerdei Körút 98, Debrecen 4012, Hungary.
authors.forename: György
authors.initials: G
authors.lastname: Trencsényi
authors.affiliation: Department of Nuclear Medicine, University of Debrecen, P.O. Box 63, Nagyerdei Körút 98, Debrecen 4012, Hungary.
authors.forename: Teréz
authors.initials: T
authors.lastname: Márián
authors.affiliation: Department of Nuclear Medicine, University of Debrecen, P.O. Box 63, Nagyerdei Körút 98, Debrecen 4012, Hungary.
authors.forename: Imre
authors.initials: I
authors.lastname: Lajtos
authors.affiliation: Department of Biophysics and Cell Biology, University of Debrecen, Nagyerdei Körút 98, Debrecen 4012, Hungary.
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Krasznai
authors.affiliation: Department of Nuclear Medicine, University of Debrecen, P.O. Box 63, Nagyerdei Körút 98, Debrecen 4012, Hungary.
authors.forename: László
authors.initials: L
authors.lastname: Balkay
authors.affiliation: Department of Nuclear Medicine, University of Debrecen, P.O. Box 63, Nagyerdei Körút 98, Debrecen 4012, Hungary.
authors.forename: Miklós
authors.initials: M
authors.lastname: Emri
authors.affiliation: Department of Nuclear Medicine, University of Debrecen, P.O. Box 63, Nagyerdei Körút 98, Debrecen 4012, Hungary.
authors.forename: Pál
authors.initials: P
authors.lastname: Mikecz
authors.affiliation: Department of Biophysics and Cell Biology, University of Debrecen, Nagyerdei Körút 98, Debrecen 4012, Hungary.
authors.forename: Katalin
authors.initials: K
authors.lastname: Goda
authors.affiliation: Department of Biophysics and Cell Biology, University of Debrecen, Nagyerdei Körút 98, Debrecen 4012, Hungary.
authors.forename: Gábor
authors.initials: G
authors.lastname: Szalóki
authors.affiliation: Department of Dermatology, University of Debrecen, Nagyerdei Körút 98, Debrecen 4012, Hungary ; Department of Surgery and Operative Techniques, Faculty of Dentistry, University of Debrecen, Nagyerdei Körút 98, Debrecen 4012, Hungary.
authors.forename: István
authors.initials: I
authors.lastname: Juhász
authors.affiliation: Department of Nuclear Medicine, University of Debrecen, P.O. Box 63, Nagyerdei Körút 98, Debrecen 4012, Hungary.
authors.forename: Enikő
authors.initials: E
authors.lastname: Németh
authors.affiliation: Department of Nuclear Medicine, University of Debrecen, P.O. Box 63, Nagyerdei Körút 98, Debrecen 4012, Hungary.
authors.forename: Tünde
authors.initials: T
authors.lastname: Miklovicz
authors.affiliation: Department of Biophysics and Cell Biology, University of Debrecen, Nagyerdei Körút 98, Debrecen 4012, Hungary.
authors.forename: Gábor
authors.initials: G
authors.lastname: Szabó
authors.affiliation: Department of Obstetrics and Gynecology, University of Debrecen, Nagyerdei Körút 98, Debrecen 4012, Hungary.
authors.forename: Zoárd T
authors.initials: ZT
authors.lastname: Krasznai
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D000818:Animals; D001345:Autoradiography; D002250:Carbon Radioisotopes; D045744:Cell Line, Tumor; D015224:Dideoxynucleosides; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D005260:Female; D005434:Flow Cytometry; D019788:Fluorodeoxyglucose F18; D005500:Follow-Up Studies; D005833:Genital Neoplasms, Female / Q000000981:diagnostic imaging* / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D008715:Methionine; D051379:Mice; D016513:Mice, SCID; D009593:Nitroimidazoles; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals; D047368:Tumor Burden; D023041:Xenograft Model Antitumor Assays
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D002250:Carbon Radioisotopes; D015224:Dideoxynucleosides; D009593:Nitroimidazoles; D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18; C498052:fluoroazomycin arabinoside; D008715:Methionine; C002854:alovudine