SPECT/CT of lung nodules using 111 In-DOTA-c(RGDfK) in a mouse lung carcinogenesis model
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ORIGINAL ARTICLE
SPECT/CT of lung nodules using 111In-DOTA-c(RGDfK) in a mouse lung carcinogenesis model Takuya Hayakawa • Michihiro Mutoh • Toshio Imai • Koji Tsuta • Akinori Yanaka Hirofumi Fujii • Mitsuyoshi Yoshimoto
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Received: 16 October 2012 / Accepted: 10 April 2013 / Published online: 23 April 2013 Ó The Japanese Society of Nuclear Medicine 2013
Abstract Objective Lung cancer is one of the leading causes of cancer-related deaths worldwide, including Japan. Although computed tomography (CT) can detect small lung lesions such as those appearing as ground glass opacity, it cannot differentiate between malignant and nonmalignant lesions. Previously, we have shown that single photon emission computed tomography (SPECT) imaging using 111In-1,4,7,10-tetraazacyclododecane-N,N0 ,N00 ,N000 tetraacetic acid-cyclo-(Arg-Gly-Asp-D-Phe-Lys) (DOTAc(RGDfK)), an imaging probe of avb3 integrin, is useful for the early detection of pancreatic cancer in a hamster pancreatic carcinogenesis model. In this study, we aimed to
T. Hayakawa M. Mutoh Division of Cancer Prevention Research, National Cancer Center Research Institute, 5-1-1 Chuo-ku, Tokyo 104-0045, Japan T. Hayakawa A. Yanaka Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan T. Imai Central Animal Division, National Cancer Center Research Institute, 5-1-1 Chuo-ku, Tokyo 104-0045, Japan K. Tsuta Division of Pathology and Clinical Laboratory, National Cancer Center Hospital, 5-1-1 Chuo-ku, Tokyo 104-0045, Japan H. Fujii M. Yoshimoto Functional Imaging Division, National Cancer Center Hospital East, 6-5-1 Kashiwanoha, Kashiwa, Chiba 277-8577, Japan M. Yoshimoto (&) Division of Cancer Development System, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan e-mail: [email protected]
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assess the usefulness of SPECT/CT with 111In-DOTAc(RGDfK) for the evaluation of the malignancy of lung cancer. Methods Lung tumors were induced by a single intraperitoneal injection (250 mg/kg) of urethane in male A/J mice. Twenty-six weeks after the urethane treatment, SPECT was performed an hour after injection of 111InDOTA-c(RGDfK). Following this, the radioactivity ratios of tumor to normal lung tissue were measured by autoradiography (ARG) in the excised lung samples. We also examined the expression of avb3 integrin in mouse and human lung samples. Results Urethane treatment induced 5 hyperplasias, 41 adenomas and 12 adenocarcinomas in the lungs of 8 A/J mice. SPECT with 111In-DOTA-c(RGDfK) could clearly visualize lung nodules, though we failed to detect small lung nodules like adenoma and hyperplasias (adenocarcinoma: 66.7 %, adenoma: 33.6 %, hyperplasia: 0.0 %). ARG analysis revealed significant uptake of 111In-DOTAc(RGDfK) in all the lesions. Moreover, tumor to normal lung tissue ratios increased along with the progression of carcinogenesis. Histopathological examination using human lung tissue samples revealed clear up-regulation of avb3 integrin in well-differentiated adenocarcin
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