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Abstract 5306: 18F-EF5 microPET imaging of treatment response from a novel, hypoxia-selective cytotoxin SN30000 in a human lung cancer xenograft model

Publication ,  Journal Article
Chitneni, SK; Bida, GT; Hay, MP; Zalutsky, MR; Melcher, T; Wilson, WR; Dewhirst, MW
Published in: Cancer Research
April 15, 2011

Introduction: SN30000 (CEN-209) is a structural analogue of the clinically tested hypoxic cell cytotoxin tirapazamine, with improved tumor penetration and increased hypoxic cell kill activity in vitro and in vivo. In this study, we investigated the use of the hypoxia PET imaging agent 18F-EF5 to measure changes in tumor hypoxia before and after treatment with SN30000 in a rat model of human non-small cell lung cancer (H460).Methods: Xenografts were established by subcutaneous injection of about 5 million H460 cells into the lower hind limb of NIH-RNu nude rats, and after 12-13 days the tumors were used for imaging experiments. Using two groups of animals we studied the changes in hypoxia at early time point (5-6 h) and at about 24 h after intraperitoneal administration of a single dose SN30000 (90 mg/kg body weight) or saline. Each group consisted of two control tumors (saline) and three SN30000 treated tumors. In both pre- and post-treatment scans, animals were scanned for 15-20 min at 2.5 h after i.v. injection 0.7-1.4 mCi of 18F-EF5. After reconstruction, PET images were analyzed by drawing regions of interest (ROI) covering whole tumor tissue and on contralateral leg muscle as background ROI. Standard uptake values (SUV) were calculated from the radioactivity concentration in both tumor and muscle tissue after normalization to the injection dose and body weight of the animal.Results: All tumors (n=10) showed tumor-to-muscle ratios (2.2 to 3.1) high enough to delineate the tumor from background activity. The SUV values in pre-treatment scans ranged from 0.43 to 0.79. No change in 18F-EF5 uptake was observed when animals were imaged at 5-6 h post-SN30000 therapy (mean SUV 0.59 ± 0.18 vs 0.59 ± 0.08 at baseline). However, tumors when imaged at 24 h after the treatment showed a decrease in tumor accumulation of 18F-EF5 by 19.7% to 54.6% when compared to pre-treatment scans (SUV 0.39 ± 0.12 vs. 0.63 ± 0.09 at baseline, p=0.06). Three out of four control tumors showed a slight increase in SUV in post-treatment scan compared to pre-treatment scan.Conclusions: The results from this study suggest that SN30000 may reduce hypoxia as measured by 18F-EF5 PET imaging at a later time point (1 day) rather than a few hours after treatment, and suggest potential use of 2-nitroimidazole-based PET imaging as an early response biomarker during clinical development of this compound.Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5306. doi:10.1158/1538-7445.AM2011-5306

Duke Scholars

Published In

Cancer Research

DOI

EISSN

1538-7445

ISSN

0008-5472

Publication Date

April 15, 2011

Volume

71

Issue

8_Supplement

Start / End Page

5306 / 5306

Publisher

American Association for Cancer Research (AACR)

Related Subject Headings

  • Oncology & Carcinogenesis
  • 3211 Oncology and carcinogenesis
  • 3101 Biochemistry and cell biology
  • 1112 Oncology and Carcinogenesis
 

Citation

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Chitneni, S. K., Bida, G. T., Hay, M. P., Zalutsky, M. R., Melcher, T., Wilson, W. R., & Dewhirst, M. W. (2011). Abstract 5306: 18F-EF5 microPET imaging of treatment response from a novel, hypoxia-selective cytotoxin SN30000 in a human lung cancer xenograft model. Cancer Research, 71(8_Supplement), 5306–5306. https://doi.org/10.1158/1538-7445.am2011-5306
Chitneni, Satish K., Gerald T. Bida, Michael P. Hay, Michael R. Zalutsky, Thorsten Melcher, William R. Wilson, and Mark W. Dewhirst. “Abstract 5306: 18F-EF5 microPET imaging of treatment response from a novel, hypoxia-selective cytotoxin SN30000 in a human lung cancer xenograft model.” Cancer Research 71, no. 8_Supplement (April 15, 2011): 5306–5306. https://doi.org/10.1158/1538-7445.am2011-5306.
Chitneni SK, Bida GT, Hay MP, Zalutsky MR, Melcher T, Wilson WR, et al. Abstract 5306: 18F-EF5 microPET imaging of treatment response from a novel, hypoxia-selective cytotoxin SN30000 in a human lung cancer xenograft model. Cancer Research. 2011 Apr 15;71(8_Supplement):5306–5306.
Chitneni, Satish K., et al. “Abstract 5306: 18F-EF5 microPET imaging of treatment response from a novel, hypoxia-selective cytotoxin SN30000 in a human lung cancer xenograft model.” Cancer Research, vol. 71, no. 8_Supplement, American Association for Cancer Research (AACR), Apr. 2011, pp. 5306–5306. Crossref, doi:10.1158/1538-7445.am2011-5306.
Chitneni SK, Bida GT, Hay MP, Zalutsky MR, Melcher T, Wilson WR, Dewhirst MW. Abstract 5306: 18F-EF5 microPET imaging of treatment response from a novel, hypoxia-selective cytotoxin SN30000 in a human lung cancer xenograft model. Cancer Research. American Association for Cancer Research (AACR); 2011 Apr 15;71(8_Supplement):5306–5306.

Published In

Cancer Research

DOI

EISSN

1538-7445

ISSN

0008-5472

Publication Date

April 15, 2011

Volume

71

Issue

8_Supplement

Start / End Page

5306 / 5306

Publisher

American Association for Cancer Research (AACR)

Related Subject Headings

  • Oncology & Carcinogenesis
  • 3211 Oncology and carcinogenesis
  • 3101 Biochemistry and cell biology
  • 1112 Oncology and Carcinogenesis