光イメージング・低酸素ＰＥＴ・灌流ＣＴの融合画像による腫瘍内低酸素状態の動態解析

• Project/Area Number: 13J03163
• Research Category: Grant-in-Aid for JSPS Fellows
• Allocation Type: Single-year Grants
• Section: 国内
• Research Field: 放射線科学
• Research Institution: Kyoto University
• Principal Investigator: 子安 翔 京都大学, 医学研究科, 特別研究員(DC1)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥3,600,000 (Direct Cost: ¥3,600,000); Fiscal Year 2015: ¥1,200,000 (Direct Cost: ¥1,200,000); Fiscal Year 2014: ¥1,200,000 (Direct Cost: ¥1,200,000); Fiscal Year 2013: ¥1,200,000 (Direct Cost: ¥1,200,000)
• Keywords: 腫瘍低酸素 / 腫瘍間質 / 18F-FMISO / 潅流CT / イメージング / CT / フルオロミソニダゾール / PET / ^<18>F-FMISO

Outline of Annual Research Achievements

三年目は、一年目、二年目に確立したイメージングパラメータを用いて腫瘍間質のイメージングと低酸素PETの結果および腫瘍間質に相当するαSMAのDAB染色と、血管内皮細胞、低酸素細胞に相当するCD31とpimonidazole の蛍光多重染色結果を解析し、本研究の方法で腫瘍間質がイメージング可能であること、腫瘍間質は必ずしも低酸素とはいえないことを示し、これらの結果を当該領域で最も権威のある学会誌である”Radiology” 誌に発表した。二年目に達成できなかった自然発癌モデルでの検証は今後の課題であるが、臨床的には新規治療薬の標的であるにもかかわらず腫瘍間質はこれまで画像化方法がなく、本研究の結果はその生体での可視化を可能にし、治療効果判定や薬剤の適応患者の選択の可能性を生む点で重要な結果である。また、これまで腫瘍間質は低酸素であるとの報告が多かったが、今回腫瘍間質にはむしろ血管が豊富で低酸素ではない領域も存在することが分かり、各々を治療標的とする際には別途評価する必要性を示唆する結果であった。また、腫瘍の悪性化や治療抵抗性の解明と改善という目的に対して低酸素誘導性因子に着目し、新たな遺伝子を同定し、その機能に関する検討も同時に行った。まだpreliminary な段階ではあるが、同遺伝子から発現されるタンパク（ここではp70と定義）は、がん細胞がp53変異を獲得した場合に低酸素誘導性因子-1の活性を上昇させて予後不良を生じる、両経路のクロストークに関与する因子である可能性が示唆された。同遺伝子は正常組織では発現量が低いこと、野生型p53発現細胞では機能が抑制されていることを考えると腫瘍特異性の高い新たなイメージングターゲットとしての可能性を持ち、さらなる解析が期待される。

Research Progress Status

27年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

27年度が最終年度であるため、記入しない。

Research Products

• [Journal Article] Evaluation of Tumor-associated Stroma and Its Relationship with Tumor Hypoxia Using Dynamic Contrast-enhanced CT and 18F Misonidazole PET in Murine Tumor Models. (2016)
  • Author(s): Koyasu, S., Tsuji, Y., Harada, H., Nakamoto, Y., Nobashi, T., Kimura, H., Sano, K., Koizumi, K., Hamaji, M., Togashi, K.
  • Journal Title: Radiology. Volume: 278 Issue: 3 Pages: 734-41
  • DOI: 10.1148/radiol.2015150416
  • Peer Reviewed / Open Access
• [Journal Article] Prognostic value of fluorine-18 fludeoxyglucose positron emission tomography parameters differs according to primary tumour location in small-cell lung cancer. (2016)
  • Author(s): Nobashi T, Koyasu S, Nakamoto Y, (他5名)
  • Journal Title: Br J Radiol. Volume: 89 Issue: 1059 Pages: 20150618-20150618
  • DOI: 10.1259/bjr.20150618
  • Peer Reviewed
• [Journal Article] Preoperative Diagnostic Strategy for Parotid Gland Tumors Using Diffusion-Weighted MRI and Technetium-99m Pertechnetate Scintigraphy: A Prospective Study. (2016)
  • Author(s): Kikuchi M, Koyasu S, Shinohara S, (他3名)
  • Journal Title: PLoS One. Volume: 11 Issue: 2 Pages: e0148973-e0148973
  • DOI: 10.1371/journal.pone.0148973
  • Open Access
• [Journal Article] Pretreatment Mean Apparent Diffusion Coefficient Is Significantly Correlated With Event-Free Survival in Patients With International Federation of Gynecology and Obstetrics Stage Ib to IIIb Cervical Cancer. (2015)
  • Author(s): Himoto Y, Fujimoto K, Kido A, Baba T, Tanaka S, Morisawa N, Koyasu S, Konishi I, Togashi K.
  • Journal Title: Int J Gynecol Cancer. Volume: 25 Issue: 6 Pages: 1079-85
  • DOI: 10.1097/igc.0000000000000445
  • Peer Reviewed
• [Journal Article] Evaluation of oxygen dependence on in vitro and in vivo cytotoxicity of photoimmunotherapy using IR-700-antibody conjugates. (2015)
  • Author(s): Kishimoto S, Bernardo M, Saito K, Koyasu S, (他3名)
  • Journal Title: Free Radic Biol Med. Volume: 85 Pages: 24-32
  • DOI: 10.1016/j.freeradbiomed.2015.03.038
  • Peer Reviewed
• [Journal Article] Obstructive sleep apnea and abdominal aortic calcification: Is there an association independent of comorbid risk factors? (2015)
  • Author(s): Tachikawa R, Koyasu S, Matsumoto T, (他9名)
  • Journal Title: Atherosclerosis. Volume: 241 Issue: 1 Pages: 6-11
  • DOI: 10.1016/j.atherosclerosis.2015.04.801
  • Peer Reviewed
• [Journal Article] Prognostic value of pretreatment 18F-FDG PET/CT parameters including visual evaluation in patients with head and neck squamous cell carcinoma. (2014)
  • Author(s): Koyasu S, Nakamoto Y, Kikuchi M, Suzuki K, Hayashida K, Itoh K, Togashi K
  • Journal Title: AJR Am J Roentgenol Volume: 202 Issue: 4 Pages: 851-858
  • DOI: 10.2214/ajr.13.11013
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] The clinical utility of reduced-distortion readout-segmented echo-planar imaging in the head and neck region: initial experience. (2014)
  • Author(s): Koyasu S, Iima M, Umeoka S, Morisawa N, Porter DA, Ito J, Le Bihan D, Togashi K
  • Journal Title: Eur Radiol. Volume: 24 Issue: 12 Pages: 3088-3096
  • DOI: 10.1007/s00330-014-3369-5
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Bifid Tail of the Pancreas with Localized Acute Pancreatitis. (2013)
  • Author(s): Koyasu S, Isoda H, Nakase H, Kodama Y, Chiba T, Toga shi K.
  • Journal Title: Magnetic Resonance in Medical Sciences. Volume: 12 Pages: 315-318
  • Peer Reviewed
• [Presentation] 大腸がんにおける新規HIF-1活性化因子とがん抑制遺伝子のクロストーク (2016)
  • Author(s): 子安 翔、森鳰 章代、Ester M. Hammond、原田 浩.
  • Organizer: 『幹細胞・癌・エピゲノム』に関する合同リトリート
  • Place of Presentation: 同志社びわこリトリートセンター, 滋賀県
  • Year and Date: 2016-03-07
• [Presentation] PET Imaging Reveals a Greater Recruitment of Zirconium-89-oxine-labeled Monocytes to Cancer and Inflammation Compared to Macrophages. (2015)
  • Author(s): Koyasu S, Asiedu K. O., Choyke P. L. and Sato N
  • Organizer: World Molecular Imaging Congress 2015
  • Place of Presentation: Hawaii Convention Center, Honolulu, Hawaii
  • Year and Date: 2015-09-02
  • Int'l Joint Research
• [Presentation] Evaluation of Tumor Hypoxia and Cancer Stroma Using 18F-misonidazole PET and Dynamic Contrast Enhanced CT in Tumor-bearing Mice Models. (2014)
  • Author(s): Sho Koyasu, Yuji Nakamoto, Hiroshi Harada, Yoshihisa Tsuji, Hiroyuki Kimura, Kohei Sano, Tomomi Nobashi, Kaori Togashi.
  • Organizer: EANM’14
  • Place of Presentation: Svenska M&#228;ssan &#8211; The Swedish Exhibition & Congress Centre, Gothenburg, Sweden
  • Year and Date: 2014-10-18 – 2014-10-22
• [Presentation] Evaluation of Tumour Hypoxia and Cancer Stroma Using 18F-misonidazole PET and Dynamic Contrast Enhanced CT in Tumor-bearing Mice Models. (2014)
  • Author(s): Sho Koyasu, Yuji Nakamoto, Hiroshi Harada, Yoshihisa Tsuji, Hiroyuki Kimura, Kohei Sano, Tomomi Nobashi, Kaori Togashi.
  • Organizer: The 15th Asian Oceanian Congress of Radiology
  • Place of Presentation: Kobe Convention Center / Kobe Portopia Hote, Kobe, Japan
  • Year and Date: 2014-09-24 – 2014-09-28
• [Presentation] Evaluation of intratumoral microenvironment with 18F-misonidazole PET and dynamic contrast enhanced CT in tumor-bearing mice models. (2014)
  • Author(s): Sho Koyasu, Yuji Nakamoto, Hiroshi Harada, Hiroyuki Kimura, Kohei Sano, Koji Koizumi, Yoshihisa Tsuji, Tomomi Nobashi, Kensuke Kurihara, Kaori Togashi.
  • Organizer: SNMMI 2014 Annual Meeting
  • Place of Presentation: St. Louis Convention Center, St. Louis, Missouri, USA
  • Year and Date: 2014-06-07 – 2014-06-11
• [Presentation] Read-Out Segmented Echo-Planar Imaging Diffusion Weighted Imaging for Evaluating Head and Neck Region. (2014)
  • Author(s): Sho Koyasu, Mami Iima, Shigeaki Umeoka, Denis Le Bihan, David A. Porte, Kaori Togashi.
  • Organizer: Joint Annual Meeting ISMRM-ESMRMB
  • Place of Presentation: Milano Congressi &#8211; Piazzale Carlo Magno, Milan, Italy
  • Year and Date: 2014-05-10 – 2014-05-16
• [Presentation] 中咽頭癌患者の予後予測におけるFDG-PET/CTの重要性 (2013)
  • Author(s): 子安 翔、中本 裕士、菊地 正弘、伊藤 亨、富樫 かおり
  • Organizer: 第53回日本核医学会学術総会
  • Place of Presentation: 福岡国際会議場(福岡市)
• [Presentation] Prognostic value of pretreatment 18F-FDG PET/CT parameters including visual evaluation in patients with head and neck sauamous cell carcinoma. (2013)
  • Author(s): Koyasu S, Nakamoto Y, Kikuchi M, Nakatani K, Togashi K.
  • Organizer: SNMMI 2013
  • Place of Presentation: Vancouver, Canada
• [Presentation] Prognostic value of 18F-FDG PET/CT parameters and human papillomavirus in patients with oropharyngeal squamous cell carcinoma. (2013)
  • Author(s): Koyasu S, Nakamoto Y, Kikuchi M, Nakatani K, Togashi K.
  • Organizer: EANM 2013
  • Place of Presentation: Lyon, France
• [Presentation] Read-Out Segmented Echo-Planar Imaging Diffusion Weighted Imaging for Evaluating Head and Neck Region. (2013)
  • Author(s): Koyasu S, Iima M, Umeoka S, Le Bihan D, and Togashi K.
  • Organizer: Taiwan University and Kyoto University Symposium
  • Place of Presentation: Taipei, Taiwan.