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Tumor Targeting via Sialic Acid: [68Ga]DOTA-en-pba as a New Tool for Molecular Imaging of Cancer with PET

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Abstract

Purpose

The aim of this study was to demonstrate the potential of Ga-68-labeled macrocycle (DOTA-en-pba) conjugated with phenylboronic vector for tumor recognition by positron emission tomography (PET), based on targeting of the overexpressed sialic acid (Sia).

Procedures

The imaging reporter DOTA-en-pba was synthesized and labeled with Ga-68 at high efficiency. Cell binding assay on Mel-C and B16-F10 melanoma cells was used to evaluate melanin production and Sia overexpression to determine the best model for demonstrating the capability of [68Ga]DOTA-en-pba to recognize tumors. The in vivo PET imaging was done with B16-F10 tumor-bearing SCID mice injected with [68Ga]DOTA-en-pba intravenously. Tumor, blood, and urine metabolites were assessed to evaluate the presence of a targeting agent.

Results

The affinity of [68Ga]DOTA-en-pba to Sia was demonstrated on B16-F10 melanoma cells, after the production of melanin as well as Sia overexpression was proved to be up to four times higher in this cell line compared to that in Mel-C cells. Biodistribution studies in B16-F10 tumor-bearing SCID mice showed blood clearance at the time points studied, while uptake in the tumor peaked at 60 min post-injection (6.36 ± 2.41 % ID/g). The acquired PET images were in accordance with the ex vivo biodistribution results. Metabolite assessment on tumor, blood, and urine samples showed that [68Ga]DOTA-en-pba remains unmetabolized up to at least 60 min post-injection.

Conclusions

Our work is the first attempt for in vivo imaging of cancer by targeting overexpression of sialic acid on cancer cells with a radiotracer in PET.

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Acknowledgements

The authors gratefully acknowledge Mr. S. Xanthopoulos (Radiochemical Studies Laboratory, INRaSTES, NCSR “Demokritos”) and Mr. E. Balafas (Laboratory Animal Facilities, Biomedical Research Foundation of the Academy of Athens) for excellent technical assistance.

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Authors and Affiliations

  1. Institute of Nuclear & Radiological Sciences & Technology, Energy & Safety, National Center for Scientific Research “Demokritos”, Aghia Paraskevi, 153 10, Athens, Greece

    Charalambos Tsoukalas, Theodoros Tsotakos, Maria Paravatou-Petsotas & Penelope Bouziotis

  2. Department of Molecular Biotechnology and Health Sciences, University of Turin, via Nizza 52, Torino, Italy

    Simonetta Geninatti-Crich & Silvio Aime

  3. Biomedical Research Foundation of the Academy of Athens, 4 Soranou Ephessiou Street, 115 27, Athens, Greece

    Anastasios Gaitanis & Constantinos D. Anagnostopoulos

  4. Department of Organic Chemistry, National School of Biological Sciences, National Polytechnical Institute, Prolongación de Carpio y Plan de Ayala S/N, 11340, Mexico D.F., Mexico

    Rogelio Jiménez-Juárez

  5. Department of Biotechnology, Delft University of Technology, Van der Maasweg, 2629 HZ, Delft, Netherlands

    Rogelio Jiménez-Juárez & Kristina Djanashvili

Authors
  1. Charalambos Tsoukalas
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  2. Simonetta Geninatti-Crich
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  3. Anastasios Gaitanis
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  4. Theodoros Tsotakos
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  5. Maria Paravatou-Petsotas
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  6. Silvio Aime
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  7. Rogelio Jiménez-Juárez
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  8. Constantinos D. Anagnostopoulos
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  9. Kristina Djanashvili
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  10. Penelope Bouziotis
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Corresponding author

Correspondence to Penelope Bouziotis.

Ethics declarations

These studies have been further approved by the Ethics Committee of the NCSR “Demokritos,” and animal care and procedures followed are in accordance with institutional guidelines and licenses issued by the Department of Agriculture and Veterinary Policies of the Prefecture of Attiki (registration numbers: EL 25 BIO 022 and EL 25 BIO 021).

Conflict of Interest

The authors declare that they have no conflict of interest.

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Tsoukalas, C., Geninatti-Crich, S., Gaitanis, A. et al. Tumor Targeting via Sialic Acid: [68Ga]DOTA-en-pba as a New Tool for Molecular Imaging of Cancer with PET. Mol Imaging Biol 20, 798–807 (2018). https://doi.org/10.1007/s11307-018-1176-0

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  • DOI: https://doi.org/10.1007/s11307-018-1176-0

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