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Targeting of the Antivascular Drug Combretastatin to Irradiated Tumors Results in Tumor Growth Delay

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Purpose

The aim of the study is to evaluate the effects of targeting the antivascular drug combretastatin to irradiated mouse melanomas.

Methods

Combretastatin was incorporated into liposomes with surfaces modified by the addition of cyclo(Arg-Gly-Asp-d-Phe-Cys) (RGD) to create an immunoliposome (IL). This addition of RGD allows the liposome to be preferentially targeted to αvβ3, an integrin up-regulated in the vasculature of irradiated tumors. C57BL mice bearing a transplanted B16-F10 melanoma were randomly assigned to one of the following treatment groups: untreated, a single dose of 5-Gy radiation (IR), IL (14.5 mg/kg of combretastatin), 5-Gy radiation plus IL, and a systemic administration of free drug (81.0 mg/kg of combretastatin).

Results

In this transplanted tumor model, there was no significant increase in the volume of the IL + IR (5 Gy) treated tumors during the initial 6 days posttreatment; all other treatment groups exhibited exponential growth curves after day 3. The IL + IR (5 Gy) treatment resulted in a 5.1-day tumor growth delay compared to untreated controls.

Conclusions

These findings indicate that preferential targeting of antivascular drugs to irradiated tumors results in significant tumor growth delay.

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Acknowledgments

This work was supported by NSF Grant BES0090009 and the Scholler Foundation. Mohammad F. Kiani is an Established Investigator of the American Heart Association. We would like to thank Dr. Stanley Kosanke (the University of Oklahoma Health Science Center) for performing the pathological examination of the tumors.

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Authors and Affiliations

  1. Department of Mechanical Engineering, Temple University, Philadelphia, Pennsylvania, USA

    Christopher B. Pattillo, Farid Sari-Sarraf & Mohammad F. Kiani

  2. Department of Pharmaceutical Science, University of Tennessee, Memphis, Tennessee, USA

    Ramakrishna Nallamothu, Bob M. Moore & George C. Wood

  3. Department of Radiation Oncology, Temple University, Philadelphia, Pennsylvania, USA

    Mohammad F. Kiani

  4. 1947 North 12th Street, Philadelphia, Pennsylvania, USA

    Mohammad F. Kiani

Authors
  1. Christopher B. Pattillo
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  2. Farid Sari-Sarraf
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  3. Ramakrishna Nallamothu
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  4. Bob M. Moore
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  5. George C. Wood
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  6. Mohammad F. Kiani
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Corresponding author

Correspondence to Mohammad F. Kiani.

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Pattillo, C.B., Sari-Sarraf, F., Nallamothu, R. et al. Targeting of the Antivascular Drug Combretastatin to Irradiated Tumors Results in Tumor Growth Delay. Pharm Res 22, 1117–1120 (2005). https://doi.org/10.1007/s11095-005-5646-0

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  • DOI: https://doi.org/10.1007/s11095-005-5646-0

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