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Amino Acids

, Volume 48, Issue 7, pp 1667–1675 | Cite as

Catabolism of 64Cu and Cy5.5-labeled human serum albumin in a tumor xenograft model

  • Choong Mo Kang
  • Hyunjung Kim
  • Hyun-Jung Koo
  • Jin Won Park
  • Gwang Il An
  • Joon Young Choi
  • Kyung-Han Lee
  • Byung-Tae Kim
  • Yearn Seong ChoeEmail author
Original Article

Abstract

Human serum albumin (HSA), the most abundant protein in blood plasma, has been used as a drug carrier for the last few decades. Residualizingly radiolabeled serum albumin has been reported to be avidly taken up by tumors of sarcoma-bearing mice and to most likely undergo lysosomal degradation. In this study, we prepared 64Cu-1,4,7,10-tetraazacyclododecane-N,N′,N″,N′″-tetraacetic acid (DOTA) and Cy5.5-conjugated HSA (dual probe), and evaluated its tumor uptake and catabolism. Two dual probes were prepared using different DOTA conjugation sites of HSA (one via Lys residues and the other via the Cys residue). 64Cu-DOTA-Lys-HSA-Cy5.5 (dual probe-Lys) exhibited higher uptake by RR1022 sarcoma cells in vitro than 64Cu-DOTA-Cys-HSA-Cy5.5 (dual probe-Cys). In RR1022 tumor-bearing mice, the two dual probes showed a similar level of tumor uptake, but uptake of dual probe-Lys was reduced in the liver and spleen compared to dual probe-Cys, probably because of the presence of a higher number of DOTA molecules in the former. At 24 and 48 h after injection, dual probe-Lys was intact or partially degraded in blood, liver, kidney, and tumor samples, but 64Cu-DOTA-Lys was observed in the urine using radioactivity detection. Similarly, Cy5.5-Lys was observed in the urine using fluorescence detection. These results indicate that dual probe-Lys may be useful for predicting the catabolic fate of drug–HSA conjugates.

Keywords

Human serum albumin PET/optical imaging 64Cu-DOTA-Lys Cy5.5-Lys Tumor Catabolism 

Notes

Acknowledgments

This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korean government (MEST) (grant code: 2011-0030164).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no competing financial interests.

Ethical approval

All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. The animal study was reviewed and approved by the Institutional Animal Care and Use Committee of SBRI. SBRI is an Association for Assessment and Accreditation of Laboratory Animal Care International accredited facility and abides by the Institute of Laboratory Animal Resources Guide.

Informed consent

This article does not contain any studies with human participants performed by any of the authors.

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Copyright information

© Springer-Verlag Wien 2016

Authors and Affiliations

  • Choong Mo Kang
    • 1
    • 2
  • Hyunjung Kim
    • 1
    • 2
  • Hyun-Jung Koo
    • 1
  • Jin Won Park
    • 1
    • 2
  • Gwang Il An
    • 3
  • Joon Young Choi
    • 1
  • Kyung-Han Lee
    • 1
    • 2
  • Byung-Tae Kim
    • 1
  • Yearn Seong Choe
    • 1
    • 2
    Email author
  1. 1.Department of Nuclear Medicine, Samsung Medical CenterSungkyunkwan University School of MedicineSeoulKorea
  2. 2.Department of Health Sciences and Technology, SAIHSTSungkyunkwan UniversitySeoulKorea
  3. 3.Molecular Imaging Research CenterKorea Institute of Radiological and Medical SciencesSeoulKorea

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