Kaohsiung Journal of Medical Sciences
Volume 24, Issue 9 , Pages 461-472, September 2008

Accumulation of Tc-99m HL91 in Tumor Hypoxia: In Vitro Cell Culture and In Vivo Tumor Model

  • Bi-Fang Lee

      Affiliations

    • Department of Nuclear Medicine, College of Medicine, National Cheng Kung University, Taiwan
    • Corresponding Author InformationAddress correspondence and reprint requests to: Dr Bi-Fang Lee, Department of Nuclear Medicine, College of Medicine, National Cheng Kung University, 138 Sheng-Li Road, Tainan 701, Taiwan
    • ,
  • Nan-Tsing Chiu

      Affiliations

    • Department of Nuclear Medicine, College of Medicine, National Cheng Kung University, Taiwan
    • ,
  • Chien-Chung Hsia

      Affiliations

    • Institute of Nuclear Energy, Lungtan, Taiwan
    • ,
  • Lie-Hang Shen

      Affiliations

    • Institute of Nuclear Energy, Lungtan, Taiwan

Received 30 November 2007; accepted 27 August 2008.

Article Outline

Hypoxic cells within a tumor can account, in part, for resistance to radiotherapy and chemotherapy. Indeed, the oxygenation status has been shown to be a prognostic marker for the outcome of therapy. The purpose of this study was to determine whether Tc-99m HL91 (HL91), a noninvasive imaging tracer, detects tumor hypoxia in vitro in cell culture and in vivo in a tumor model. Uptake of HL91 in vitro into human lung cancer cells (A549) and murine Lewis lung cancer cells (LL2) was investigated at oxygen concentrations of 20% O2 (normoxia), and 1% O2 (hypoxia). HL91 biodistribution was studied in four groups: severe combined immune deficiency (SCID) mice bearing A549 tumors, C57BL/6NCrj (B6) mice bearing LL2 tumors, SCID controls, and B6 controls. Accumulation of the tracer was compared between tumors treated with hydralazine or phosphate-buffered saline (PBS). Scintigraphic images were obtained for hydralazine-treated mice and PBS-treated mice in each of the four study groups. Autoradiography of tumor slices was also acquired. In vitro studies identified hypoxia-selective uptake of HL91, with significantly increased uptake in the hypoxic state than in the normoxic state. Biodistribution and scintigraphy showed increased HL91 uptake during tumor hypoxia at 0.5 hours, and there was progressively increased activity for up to 4 hours after tracer administration. HL91 accumulation in tumor hypoxia was markedly increased in mice treated with hydralazine compared with those treated with PBS. Autoradiography revealed high HL91 uptake in the peripheral areas around the necrotic regions of the tumor, which were identified by histologic examination. HL91 exhibits selectivity for tumor hypoxia both in vitro and in vivo and provides a successful imaging modality for the detection of tumor hypoxia in vivo.

Key Words:  in vitro , in vivo , scintigraphy , Tc-99m HL91 , tumor hypoxia

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PII: S1607-551X(09)70003-8

doi:10.1016/S1607-551X(09)70003-8

Kaohsiung Journal of Medical Sciences
Volume 24, Issue 9 , Pages 461-472, September 2008

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