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Efficient Construction of PET/Fluorescence Probe Based on Sarcophagine Cage: An Opportunity to Integrate Diagnosis with Treatment

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Abstract

Purpose

Due to the shortage of established platforms/methods for multimodality probe construction, in this study, we developed a heterofunctional chelator, BaAn(Boc)Sar, from sarcophagine cage as a general platform for dual-modality probe construction.

Procedures

A dual-modality probe for positron-emission tomography (PET) and fluorescence imaging was synthesized using the developed BaAn(Boc)Sar chelator. The c(RGDyK)2 peptide (denoted as RGD2) and fluorescence dye Cy5.5 were conjugated with BaAn(Boc)Sar to form BaAnSar-RGD2-Cy5.5. Then, BaAnSar-RGD2-Cy5.5 was labeled with 64Cu in ammonium acetate buffer. PET and fluorescent imaging were carried out to evaluate 64Cu-BaAnSar-RGD2-Cy5.5 in nude mice bearing U87MG glioblastoma xenograft.

Results

The BaAnSar-RGD2-Cy5.5 was labeled with 64Cu very efficiently in 0.1 M NH4OAc buffer within 10 min at 37 °C in the yield of 86.7 ± 4.4 % (n = 3). The specific activity of 64Cu-BaBaSar-RGD2 was controlled at 50–200 mCi/μmol for the consideration of both PET and optical imaging. MicroPET quantification analysis shows that the U87MG tumor uptake is 6.41 ± 0.28, 6.51 ± 1.45, and 5.92 ± 1.57 %ID/g at 1, 4, and 20 h postinjection, respectively. Good correlation was obtained between the tumor to muscle ratios measured by the radioactivity and fluorescence intensity. As a proof of concept, an animal surgery study demonstrated that this dual-modality probe would greatly benefit the patients because the PET moiety could be used for tumor detection, and the fluorescent moiety would allow image-guided surgery.

Conclusions

Our findings demonstrated the effectiveness and feasibility of preparing dual-modality imaging probes based on the sarcophagine scaffold. The resulting PET and fluorescent imaging probe also holds a great potential for clinical translation.

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Acknowledgments

This work was supported by the Department of Energy (DE-SC0002353), the National Cancer Institute (P30CA014089), the American Cancer Society (121991-MRSG-12-034-01-CCE), National Natural Science Foundation of Guangdong (no. U1032002), National Natural Science Foundation of China (no.81071206), and the USC Biomedical Imaging Science Initiative.

Conflict of Interest

The authors have declared that they have no conflict of interest.

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Authors and Affiliations

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

    Shuanglong Liu, Dan Li, Chiun-Wei Huang, Li-Peng Yap, Ryan Park, Zibo Li & Peter S. Conti

  2. Department of Radiology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510630, China

    Dan Li & Hong Shan

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  1. Shuanglong Liu
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  2. Dan Li
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  3. Chiun-Wei Huang
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  4. Li-Peng Yap
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  5. Ryan Park
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  6. Hong Shan
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  7. Zibo Li
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  8. Peter S. Conti
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Corresponding authors

Correspondence to Zibo Li or Peter S. Conti.

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Liu, S., Li, D., Huang, CW. et al. Efficient Construction of PET/Fluorescence Probe Based on Sarcophagine Cage: An Opportunity to Integrate Diagnosis with Treatment. Mol Imaging Biol 14, 718–724 (2012). https://doi.org/10.1007/s11307-012-0557-z

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  • DOI: https://doi.org/10.1007/s11307-012-0557-z

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