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Tumor Uptake of Hollow Gold Nanospheres After Intravenous and Intra-arterial Injection: PET/CT Study in a Rabbit VX2 Liver Cancer Model

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Abstract

Purpose

This study was designed to investigate the intratumoral uptake of hollow gold nanospheres (HAuNS) after hepatic intra-arterial (IA) and intravenous (IV) injection in a liver tumor model.

Materials and methods

Fifteen VX2 tumor-bearing rabbits were randomized into five groups (n = 3 in each group) that received either IV 64Cu-labeled PEG-HAuNS (IV-PEG-HAuNS), IA 64Cu-labeled PEG-HAuNS (IA-PEG-HAuNS), IV cyclic peptide (RGD)-conjugated 64Cu-labeled PEG-HAuNS (IV-RGD-PEG-HAuNS), IA RGD-conjugated 64Cu-labeled PEG-HAuNS (IA-RGD-PEG-HAuNS), or IA 64Cu-labeled PEG-HAuNS with lipiodol (IA-PEG-HAuNS-lipiodol). The animals underwent PET/CT 1 h after injection, and uptake expressed as percentage of injected dose per gram of tissue (%ID/g) was measured in tumor and major organs. The animals were euthanized 24 h after injection, and tissues were evaluated for radioactivity.

Results

At 1 h after injection, animals in the IA-PEG-HAuNS-lipiodol group showed significantly higher tumor uptake (P < 0.001) and higher ratios of tumor-to-normal liver uptake (P < 0.001) than those in all other groups. The biodistribution of radioactivity 24 h after injection showed that IA delivery of PEG-HAuNS with lipiodol resulted in the highest tumor uptake (0.33 %ID/g; P < 0.001) and tumor-to-normal liver ratio (P < 0.001) among all delivery methods. At 24 h, the IA-RGD-PEG-HAuNS group showed higher tumor uptake than the IA-PEG-HAuNS group (0.20 vs. 0.099 %ID/g; P < 0.001).

Conclusion

Adding iodized oil to IA-PEG-HAuNS maximizes nanoparticle delivery to hepatic tumors and therefore may be useful in targeted chemotherapy and photoablative therapy. PET/CT can be used to noninvasively monitor the biodistribution of radiolabeled HAuNS after IV or IA injection.

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Acknowledgments

This research was supported in part by the National Institutes of Health grants CA119387 and GM092599, by a grant from the John S. Dunn Research Foundation.

Conflict of interest

None of the authors have any conflict of interest related to this manuscript.

Author information

Author notes

  1. Mei Tian

    Present address: Department of Nuclear Medicine and Medical PET Center, The Second Hospital of Zhejiang University School of Medicine, 88 Jiefang Road, Hangzhou, Zhejiang, 310009, China

Authors and Affiliations

  1. Department of Experimental Diagnostic Imaging, University of Texas M.D. Anderson Cancer Center, Houston, TX, USA

    Mei Tian, Wei Lu, Rui Zhang, Chiyi Xiong & Chun Li

  2. Biostatistics, University of Texas M.D. Anderson Cancer Center, Houston, TX, USA

    Joe Ensor

  3. Department of Diagnostic Radiology, University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 1471, Houston, TX, 77030, USA

    Javier Nazario, Colette Shaw, Katherine A. Dixon, Kenneth Wright & Sanjay Gupta

  4. Department of Nuclear Medicine, University of Texas M.D. Anderson Cancer Center, Houston, TX, USA

    James Jackson

  5. Department of Veterinary Medicine and Surgery, University of Texas M.D. Anderson Cancer Center, Houston, TX, USA

    Jennifer Miller

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Correspondence to Mei Tian or Sanjay Gupta.

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Mei Tian and Wei Lu: contributed equally to this work.

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Tian, M., Lu, W., Zhang, R. et al. Tumor Uptake of Hollow Gold Nanospheres After Intravenous and Intra-arterial Injection: PET/CT Study in a Rabbit VX2 Liver Cancer Model. Mol Imaging Biol 15, 614–624 (2013). https://doi.org/10.1007/s11307-013-0635-x

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