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Molecular Imaging and Biology
Published in: Molecular Imaging and Biology 2/2010

01-04-2010 | Research Article

[11C]Gefitinib ([11C]Iressa): Radiosynthesis, In Vitro Uptake, and In Vivo Imaging of Intact Murine Fibrosarcoma

Authors: Ming-Rong Zhang, Katsushi Kumata, Akiko Hatori, Nobuhiko Takai, Jun Toyohara, Tomoteru Yamasaki, Kazuhiko Yanamoto, Joji Yui, Kazunori Kawamura, Sachiko Koike, Koichi Ando, Kazutoshi Suzuki

Published in: Molecular Imaging and Biology | Issue 2/2010

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Abstract

Objective

Gefitinib (N-(3-chloro-4-fluorophenyl)-7-methoxy-6-[3-(morpholin-4-yl)propoxy]quinazolin-4-amine, Iressa) is an approved anticancer drug. In this study, we labeled gefitinib with carbon-11 and evaluated [11C]gefitinib to explore its specific binding in intact fibrosarcoma (NFSa)-bearing mice.

Methods

[11C]Gefitinib was synthesized by the reaction of desmethyl precursor (1) with [11C]CH3I. In vitro uptake of [11C]gefitinib into NFSa, human-A431 epidermoid carcinoma, and Jurkat T cells was determined. Positron emission tomography (PET) imaging using [11C]gefitinib was performed for NFSa-bearing mice.

Results

[11C]Gefitinib accumulated into NFSa cells with 2.1 uptake ratio (UR)/mg protein in cells. Addition of nonradioactive gefitinib decreased uptake in a concentration-dependent manner. [11C]Gefitinib also had high uptake (2.6 UR/mg protein) into epidermal growth factor receptor/tyrosine kinase (EGFR/TK)-rich A431 cells but low uptake (0.2 UR/mg protein) into EGFR/TK-poor Jurkat cells. In vivo distribution study on NFSa-bearing mice by the dissection method revealed that [11C]gefitinib specifically accumulated into the tumor. The ratio of radioactivity in tumors to that in blood and muscle as two comparative regions increased from 0.4 to 6.0 and from 0.6 to 5.0 during this experiment (0–60 min), respectively. PET for NFSa-bearing mice produced a clear tumor image, although high radioactivity was distributed throughout the body. Treatment with nonradioactive gefitinib (100 mg/kg) decreased uptake in the tumor. In vivo metabolite analysis demonstrated that [11C]gefitinib was stable in the tumor, liver, kidney, and blood.

Conclusion

These results demonstrated the promising potential of [11C]gefitinib to serve as a PET ligand for in vivo imaging of NFSa-bearing mice.
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Metadata
Title
[11C]Gefitinib ([11C]Iressa): Radiosynthesis, In Vitro Uptake, and In Vivo Imaging of Intact Murine Fibrosarcoma
Authors
Ming-Rong Zhang
Katsushi Kumata
Akiko Hatori
Nobuhiko Takai
Jun Toyohara
Tomoteru Yamasaki
Kazuhiko Yanamoto
Joji Yui
Kazunori Kawamura
Sachiko Koike
Koichi Ando
Kazutoshi Suzuki
Publication date
01-04-2010
Publisher
Springer-Verlag
Published in
Molecular Imaging and Biology / Issue 2/2010
Print ISSN: 1536-1632
Electronic ISSN: 1860-2002
DOI
https://doi.org/10.1007/s11307-009-0265-5

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