Journal of Radiopharmaceuticals and Molecular Probes (대한방사성의약품학회지)

Korean Society of Radiopharmaceuticals and Molecular Probes (대한방사성의약품학회)
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Synthesis of a PEGylated tracer for radioiodination and evaluation of potential in tumor targeting

  • Abhinav Bhise (Department of Molecular Medicine, Brain Korea 21 Four KNU Convergence Educational Program of Biomedical Sciences for Creative Future Talents, School of Medicine, Kyungpook National University) ;
  • Sushil K Dwivedi (Department of Molecular Medicine, Brain Korea 21 Four KNU Convergence Educational Program of Biomedical Sciences for Creative Future Talents, School of Medicine, Kyungpook National University) ;
  • Kiwoong Lee (Department of Molecular Medicine, Brain Korea 21 Four KNU Convergence Educational Program of Biomedical Sciences for Creative Future Talents, School of Medicine, Kyungpook National University) ;
  • Jeong Eun Lim (Department of Molecular Medicine, Brain Korea 21 Four KNU Convergence Educational Program of Biomedical Sciences for Creative Future Talents, School of Medicine, Kyungpook National University) ;
  • Subramani Rajkumar (Department of Molecular Medicine, Brain Korea 21 Four KNU Convergence Educational Program of Biomedical Sciences for Creative Future Talents, School of Medicine, Kyungpook National University) ;
  • Woonghee Lee (Department of Molecular Medicine, Brain Korea 21 Four KNU Convergence Educational Program of Biomedical Sciences for Creative Future Talents, School of Medicine, Kyungpook National University) ;
  • Seong Hwan Cho (Department of Molecular Medicine, Brain Korea 21 Four KNU Convergence Educational Program of Biomedical Sciences for Creative Future Talents, School of Medicine, Kyungpook National University) ;
  • Jeongsoo Yoo (Department of Molecular Medicine, Brain Korea 21 Four KNU Convergence Educational Program of Biomedical Sciences for Creative Future Talents, School of Medicine, Kyungpook National University)
  • Received : 2021.11.16
  • Accepted : 2021.12.28
  • Published : 2021.12.30
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Abstract

Radiopharmaceuticals are important for tumor diagnosis and therapy. To deliver a radiotracer at the desired target excluding non-targeted tissues is difficult The development of a targeted tracer that has a good clearance profile while maintaining high biostability and biocompatibility is key to optimizing its biodistribution and transport across biological barriers. Improving the hydrophilicity of radiotracers by PEGylation can reduce serum binding, allowing the tracer to circulate without retention and reducing its affinity for non-targeted tissues. In this study, we synthesized a new benzamido tracer (SnBz-PEG36) with the introduction of a low molecular weight polyethylene glycol unit (PEG36, ~2,100 Da). The tumor targeting efficiency and biodistribution of [131I]-Bz-PEG36 or radiotracer-loaded liposomes were evaluated after their administration to normal mice or mouse tumor models including CT26 (xenograft) and 4T1 (xenograft and orthotopic). Most of the radiotracer was cleared out rapidly (1-24 h post-administration) through the kidney and there was little tumor uptake.

Keywords

Acknowledgement

This work was supported by an R&D program through the National Research Foundation of Korea funded by the Ministry of Science, ICT & Future Planning (Nos.2019H1D3A1A01102643 and 2020R1C1C1008442).

References

  1. Rosenblum D, Joshi N, Tao W, M. Karp J, Peer D. Progress and challenges towards targeted delivery of cancer therapeutics. Nature communications 2018;9:1410.
  2. Hall JE, Guyton and Hall Textbook of Medical Physiolog. TWELFTH ed. Elsevier Health Sciences; 2010. p. 310-313.
  3. Haraldsson B, Nystrcm J, Deen WM. Properties of the Glomerular Barrier and Mechanisms of Proteinuria. Physiol Rev 2008;88,451-487. https://doi.org/10.1152/physrev.00055.2006
  4. Du B, Yu M, Zheng J. Transport and interactions of nanoparticles in the kidneys. Nat Rev Mater 2018;3:358-374. https://doi.org/10.1038/s41578-018-0038-3
  5. Wang K, Kestenbaum B. Proximal Tubular Secretory Clearance A Neglected Partner of Kidney Function. Clin J Am Soc Nephrol 2018;13:1291-1296.
  6. Bradbury MS, Phillips E, Montero PH, Cheal SM, Stambuk H, Durack JC, Sofocleous CT, Meester RJ, Wiesner U, Patel S. Clinically-translated silica nanoparticles as dual-modality cancer-targeted probes for image-guided surgery and interventions. Integr Biol 2013;5:74-86. https://doi.org/10.1039/c2ib20174g
  7. Du B, Chong Y, Jiang X, Yu M, Lo U, Dang A, Chen Y, Li S, Hernandez E, Lin JC, Hsieh J, Zheng J. Hyperfluorescence Imaging of Kidney Cancer Enabled by Renal Secretion Pathway Dependent Efflux Transport. Angew Chem Int Ed 2021;60:351-359 https://doi.org/10.1002/anie.202010187
  8. Pattni BS, Chupin VV, Torchilin VP. New Developments in Liposomal Drug Delivery. Chem Rev 2015;115:10938-10966. https://doi.org/10.1021/acs.chemrev.5b00046
  9. Kluza E, Jacobs I, Hectors SJCG, Mayo KH, Griffioen AW, Strijkers GJ, Nicolay K. Dual-targeting of αvβ3 and galectin-1 improves the specificity of paramagnetic/fluorescent liposomes to tumor endothelium in vivo. J Controlled Release 2012;158:207-214. https://doi.org/10.1016/j.jconrel.2011.10.032
  10. Torchilin VP. Recent advances with liposomes as pharmaceutical carriers. Nat Rev Drug Discovery 2005;4:145-160. https://doi.org/10.1038/nrd1632
  11. Louie A. Multimodality Imaging Probes: Design and Challenges. Chem Rev 2010;110:3146-3195. https://doi.org/10.1021/cr9003538
  12. Lee W, An GI, Park H, Sarkar S, Ha YS, Huynh PT, Bhise A, Bhatt N, Ahn H, Pandya DN, Kim JY, Kim S, Jun E, Kim SC, Lee KC, Yoo J. Imaging Strategy that Achieves Ultrahigh Contrast by Utilizing Differential Esterase Activity in Organs: Application in Early Detection of Pancreatic Cancer. ACS Nano 2021;15:17348-17360. https://doi.org/10.1021/acsnano.1c05165