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The novel preparation of 99mTc(I)-labeled human serum albumin (HSA) nanoparticles as a SPECT imaging agent

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Abstract

The purpose of this study was to develop a convenient and robust method for preparation of 99mTc(I)-labeled human serum albumin nanoparticles (HSA-NPs) as a SPECT agent for tumor imaging. Efficient radiolabeling 99mTc to HSA-NPs was achieved by simply reacting [99mTc(OH2)3(CO)3]+ with the reconstituted HSA-NPs solution. The size and morphology of 99mTc(I)-HSA-NPs were analyzed and found not to significantly change after the preformed HSA-NPs were lyophilized or labeled with 99mTc(I). By incubating 99mTc(I)-HSA-NPs in rat plasma at 37 °C for 30 h, 75 % of the radioactivity were found to be remained in the particles, suggesting good in vitro stability.

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References

  1. Peer D, Karp JM, Hong S, Farokhzad OC, Margalit R, Langer R (2007) Nanocarriers as an emerging platform for cancer therapy. Nat Nanotechnol 2(12):751–760

    Article  CAS  Google Scholar 

  2. Hawkins MJ, Soon-Shiong P, Desai N (2008) Protein nanoparticles as drug carriers in clinical medicine. Adv Drug Deli Rev 60(8):876–885

    Article  CAS  Google Scholar 

  3. Wang G, Uludag H (2008) Recent developments in nanoparticle-based drug delivery and targeting systems with emphasis on protein-based nanoparticles. Expert Opin Drug Deli 5(5):499–515

    Article  CAS  Google Scholar 

  4. Jahanshahi M, Babaei Z (2008) Protein nanoparticle: a unique system as drug delivery vehicles. Afr J Biotechnol 7(25):4926–4934

    CAS  Google Scholar 

  5. Elsadek B, Kratz F (2012) Impact of albumin on drug delivery—new applications on the horizon. J Control Release 157(1):4–28

    Article  CAS  Google Scholar 

  6. Kratz F, Elsadek B (2012) Clinical impact of serum proteins on drug delivery. J Control Release 161(2):429–445

    Article  CAS  Google Scholar 

  7. Peters T Jr (1985) Serum Albumin. Adv Protein Chem 37:161–245

    Article  CAS  Google Scholar 

  8. Kratz F (2008) Albumin as a drug carrier: design of prodrugs, drug conjugates and nanoparticles. J Control Release 132(3):171–183

    Article  CAS  Google Scholar 

  9. Saha GB (2010) Fundamentals of nuclear pharmacy, 6th edn. Springer, New York

  10. Fang J, Nakamura H, Maeda H (2011) The EPR effect: unique features of tumor blood vessels for drug delivery, factors involved, and limitations and augmentation of the effect. Adv Drug Deliver Rev 63(3):136–151

    Article  CAS  Google Scholar 

  11. Huang FYJ, Lee TW, Kao CH, Chang CH, Zhang X, Lee WY, Chen WJ, Wang SC, Lo JM (2011) Imaging, autoradiography, and biodistribution of 188Re-labeled PEGylated nanoliposome in orthotopic glioma bearing rat model. Cancer Biother Radiopharm 26(6):717–725

    Article  CAS  Google Scholar 

  12. Rhodes BA (1991) Direct labeling of proteins with 99mTc. Nucl Med Biol 18(7):667–676

    CAS  Google Scholar 

  13. Sattelberger AP, Atcher RW (1999) Nuclear medicine finds the right chemistry. Nat Biotechnol 17(9):849–850

    Article  CAS  Google Scholar 

  14. Schibli R, Schubiger PA (2002) Current use and future potential of organometallic radiopharmaceuticals. Eur J Nucl Med Mol Imaging 29(11):1529–1542

    Article  CAS  Google Scholar 

  15. Anhorn MG, Mahler HC, Langer K (2008) Freeze drying of human serum albumin (HSA) nanoparticles with different excipients. Int J Pharm 363(1–2):162–169

    Article  CAS  Google Scholar 

  16. Storp B, Engel A, Boeker A, Ploeger M, Langer K (2012) Albumin nanoparticles with predictable size by desolvation procedure. J Microencapsul 29(2):138–146

    Article  Google Scholar 

  17. Langer K, Balthasar S, Vogel V, Dinauer N, von Briesen H, Schubert D (2003) Optimization of the preparation process for human serum albumin (HSA) nanoparticles. Int J Pharm 257(1–2):169–180

    Article  CAS  Google Scholar 

  18. Langer K, Anhorn MG, Steinhauser I, Dreis S, Celebi D, Schrickel N, Faust S, Vogel V (2008) Human serum albumin (HSA) nanoparticles: reproducibility of preparation process and kinetics of enzymatic degradation. Int J Pharm 347(1–2):109–117

    Article  CAS  Google Scholar 

  19. Alberto R, Schibli R, Egli A, Schubiger AP, Abram U, Kaden TA (1998) A novel organometallic aqua complex of technetium for the labeling of biomolecules: synthesis of [99mTc(OH2)3(CO)3]+ from [99mTcO4] in aqueous solution and its reaction with a bifunctional ligand. J Am Chem Soc 120(31):7987–7988

    Article  CAS  Google Scholar 

  20. Chen WJ, Yen CL, Lo ST, Chen KT, Lo JM (2008) Direct 99mTc labeling of Herceptin (trastuzumab) by 99mTc(I) tricarbonyl ion. Appl Radiat Isot 66(3):340–345

    Article  CAS  Google Scholar 

  21. Lo JM, Pillai MR, John CS, Troutner DE (1990) Labeling of human serum albumin with 105Rh-cysteine complexes. Appl Radiat Isot 41(1):63–67

    Article  CAS  Google Scholar 

  22. Wang W, Huang Y, Zhao S, Shao T, Cheng Y (2013) Human serum albumin (HSA) nanoparticles stabilized with intermolecular disulfide bonds. Chem Commun 49(22):2234–2236

    Article  CAS  Google Scholar 

  23. Carter DC, Ho JX (1994) Structure of serum albumin. Adv Protein Chem 45:153–203

    Article  CAS  Google Scholar 

  24. Chi EY, Krishnan S, Randolph TW, Carpenter JF (2003) Physical stability of proteins in aqueous solution: mechanism and driving forces in nonnative protein aggregation. Pharm Res 20(9):1325–1336

    Article  CAS  Google Scholar 

  25. Alberto R, Schibli R, Waibel R, Abram U, Schubiger AP (1999) Basic aqueous chemistry of [M(OH2)3(CO)3]+ (M = Re, Tc) directed towards radiopharmaceutical application. Coord Chem Rev 192:901–919

    Article  Google Scholar 

  26. Abram U, Alberto R (2006) Technetium and rhenium—coordination chemistry and nuclear medical applications. J Braz Chem Soc 17(8):1486–1500

    Article  CAS  Google Scholar 

  27. Egli A, Alberto R, Tannahill L, Schibli R, Abram U, Schaffland A, Waibel R, Tourwe D, Jeannin L, Iterbeke K, Schubiger PA (1999) Organometallic 99mTc-aquaion labels peptide to an unprecedented high specific activity. J Nucl Med 40(11):1913–1917

    CAS  Google Scholar 

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Acknowledgments

This work was supported by Institute of Nuclear Energy Research in Taiwan, National Tsing Hua University, and Ministry of Science and Technology, Taiwan (102-2113-M-007-006-MY2). The authors are grateful to Mrs. Shang-Fang Chang, Instrumentation Center, National Tsing Hua University, Hsinchu, Taiwan, for excellent technical assistance with TEM. The authors wish to acknowledge members in the radiopharmacology laboratory, Division of Isotope Application, Institute of Nuclear Energy Research, Longtan, Taiwan, for the expert technical assistance and helpful discussion. The authors also would like to thank Prof. Bor-Tsung Hsieh, Department of Medical imaging and Radiological Sciences, Central Taiwan University of Science and Technology, Taichung, Taiwan, for supplying a freeze-dryer, and Dr. Kai-Yuan Tzen, Department of Nuclear Medicine, National Taiwan University Hospital, Taipei, Taiwan, for generously providing 99Mo-99mTc generators in this study.

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Correspondence to Chien-Wen Chang or Jem-Mau Lo.

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Wan-Jou Chen and Feng-Yun J. Huang have contributed equally to this work.

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Chen, WJ., Huang, FY.J., Chang, HY. et al. The novel preparation of 99mTc(I)-labeled human serum albumin (HSA) nanoparticles as a SPECT imaging agent. J Radioanal Nucl Chem 307, 141–150 (2016). https://doi.org/10.1007/s10967-015-4094-5

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  • DOI: https://doi.org/10.1007/s10967-015-4094-5

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