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Longitudinal MicroPET Imaging of Brain Tumor Growth with F-18-labeled RGD Peptide

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Abstract

Purpose

EMD 121974, a potent cyclic RGD peptide inhibitor of α v-integrins, demonstrated effectiveness in suppressing brain tumor growth in both preclinical models and phases I/II clinical trials. The ability to non-invasively evaluate α v-integrin expression provides a novel and unique way to better understand brain tumor angiogenesis in relationship to α v-integrin expression, and allow for direct assessment of anti-integrin treatment efficacy.

Procedures

We developed a F-18-labeled RGD peptide [F-18]FB-RGD and performed serial microPET imaging scans to follow brain tumor growth and angiogenesis as a function of time in an orthotopic U87MG glioblastoma xenograft model in athymic nude mice.

Results

The tumor was barely visible on microPET at the size of ≤1.5 mm diameter at which time no angiogenesis was evident on histological examination. When tumor started to grow exponentially by day 35 the activity accumulation in the brain tumor also increased accordingly, with best tumor-to-brain contrast seven weeks after inoculation of 105 U87MG cells into the mice forebrain.

Conclusions

Longitudinal microPET imaging and [F-18]FB-RGD provides the sensitivity and resolution to visualize and quantify anatomical variations during brain tumor growth and angiogenesis, most likely through interaction with α v-integrins expressed on tumor cells and angiogenic tumor vessels.

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Acknowledgments

The USC cyclotron team, particularly Joseph Cook and Luis Pedroza are acknowledged for routine [F-18]F− production. This work was supported, in part, by National Institute of Biomedical Imaging and Bioengineering (NIBIB) Grant R21 EB001785, Department of Defense (DOD) Breast Cancer Research Program (BCRP) Concept Award DAMD17-03-1-0752, DOD BCRP IDEA Award W81XWH-04-1-0697, DOD Prostate Cancer Research Program (PCRP) New Investigator Award (NIA) DAMD1717-03-1-0143, American Lung Association California (ALAC), the Society of Nuclear Medicine Education and Research Foundation, National Cancer Institute (NCI) Small Animal Imaging Resource Program (SAIRP) grant R24 CA93862, and NCI in vivo Cellular Molecular Imaging Center (ICMIC) grant P50 CA114747.

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Author notes

  1. Xiaoyuan Chen PhD

    Present address: Molecular Imaging Program at Stanford, Department of Radiology, Stanford University, 1201 Welch Rd, P095, Stanford, CA, 94305-5484, USA

Authors and Affiliations

  1. PET Imaging Science Center, Department of Radiology, University of Southern California Keck School of Medicine, Los Angeles, CA, 90033, USA

    Xiaoyuan Chen PhD, Ryan Park BS, Michel Tohme MS, James R. Bading PhD & Peter S. Conti MD, PhD

  2. Department of Pediatrics, Children’s Hospital Los Angeles, Los Angeles, CA, 90027, USA

    Vazgen Khankaldyyan BS, Ignacio Gonzales-Gomez MD, Rex A. Moats PhD & Walter E. Laug MD

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  1. Xiaoyuan Chen PhD
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  2. Ryan Park BS
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  9. Peter S. Conti MD, PhD
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Correspondence to Xiaoyuan Chen PhD.

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Chen, X., Park, R., Khankaldyyan, V. et al. Longitudinal MicroPET Imaging of Brain Tumor Growth with F-18-labeled RGD Peptide. Mol Imaging Biol 8, 9–15 (2006). https://doi.org/10.1007/s11307-005-0024-1

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  • DOI: https://doi.org/10.1007/s11307-005-0024-1

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