Journal of Radiopharmaceuticals and Molecular Probes (대한방사성의약품학회지)

Korean Society of Radiopharmaceuticals and Molecular Probes (대한방사성의약품학회)
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Development & Assessment of Alkyl Chain Modified Aptamers as Potential PET Radiotracers for Lymphoma Diagnosis

  • Ji Woong Lee (Department of Medical Laboratory Science, Seoyeong University) ;
  • Un Chol Shin (School of Health and Environmental Science, College of Health Sciences, Korea University) ;
  • Seok u Bae (Major in Clinical Laboratory Science Department of Health and Safety Convergence Science, Korea University) ;
  • Ji Yoon Kim (Department of Nuclear Medicine, Seoul National University College of Medicine, College of Medicine) ;
  • Hae joon Cho (Major in Clinical Laboratory Science Department of Health and Safety Convergence Science, Korea University) ;
  • Ji Ae Park (Division of Applied RI, Korea Institute Radiological and Medical Sciences) ;
  • Kyo Chul Lee (Division of Applied RI, Korea Institute Radiological and Medical Sciences) ;
  • Jung Young Kim (Division of Applied RI, Korea Institute Radiological and Medical Sciences) ;
  • Suhng Wook Kim (School of Health and Environmental Science, College of Health Sciences, Korea University)
  • Received : 2022.12.03
  • Accepted : 2022.12.13
  • Published : 2022.12.30
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Abstract

The Td05 and Sgc8c, DNA-based aptamers, are well-known to target internalized surface markers (IGHM and PTK7) of Burkitt's lymphoma and acute lymphoblastic leukemia (ALL). Thus, Td05 and Sgc8c labeled with metallic radioisotope 64Cu can be evaluated as potential diagnostic PET imaging agents. In this study, we modified the carbon chain length of the last adenosine of aptamer (n = 3, 6, 12) to increase tumor cell uptake and select the best candidate among six types of aptamer analogues and one adenosine of aptamer. After labeling of 64Cu, [64Cu]Cu-DOTA-aptamer analogues were evaluated in vitro studies (serum stability, Log P values, cell uptake, biodistribution). Then, we evaluate in vivo PET imaging study for two candidates (64Cu-DOTA-C12-Sgc8c, 64Cu-DOTA-C6-Td05). PET images clearly visualize tumors at 24 h post-injection rather than at an early time point and the tumor-to-background ratio also increases at the delay time point. 64Cu-DOTA-C12-Sgc8c and 64Cu-DOTA-C6-Td05 could be used as potential radiotracers for lymphoma.

Keywords

Acknowledgement

This work was supported by Nuclear Research and Development Program of the National Research Foundation of Korea (NRF) grant funded by the Ministry of Science, ICT & Future Planning, Republic of Korea (NRF2021M2E7A1079168) and this research was financially supported by the Ministry of Trade, Industry and Energy, Korea, under the "Regional innovation Cluster Development Program (R&D, P0015344)" supervised by the Korea Institute for Advancement of Technology (KIAT).

References

  1. Ellington AD, Szostak JW. In vitro selection of RNA molecules that bind specific ligands, Nature 1990;346:818-22. https://doi.org/10.1038/346818a0
  2. Rockey WM, Huang L, Kloepping KC, Baumhover NJ, Giangrande PH, Schultz MK. Synthesis and radiolabeling of chelator-RNA aptamer bioconjugates with copper-64 for targeted molecular imaging. Bioorg Med Chem 2011;19:4080-90. https://doi.org/10.1016/j.bmc.2011.05.010
  3. Daniels DA, Chen H, Hicke BJ, Gold L. A tenascin-C aptamer identified by tumor cell SELEX: systematic evolution of ligands by exponential enrichment. Proc Natl Acad Sci USA 2003;100:15416-21. https://doi.org/10.1073/pnas.2136683100
  4. McNamara JO, Kolonias D, Pastor F, Mitter RS, Chen L, Giangrande PH, Sullenger B, Gilboa E. Multivalent 4-1BB binding aptamers costimulate CD8+ T cells and inhibit tumor growth in mice. Clin Invest 2008;118:376-86. https://doi.org/10.1172/JCI33365
  5. Younes CK, Boisgard R, Tavitian B. Labelled oligonucleotides as radiopharmaceuticals: pitfalls, problems and perspectives. Curr Pharm Des 2002;8(16):1451-66. https://doi.org/10.2174/1381612023394467
  6. Tavitian B. In vivo imaging with oligonucleotides for diagnosis and drug development. Gut 2003;52(Suppl 4): iv40-7. https://doi.org/10.1136/gut.52.suppl_4.iv40
  7. Zhou J, Rossi JJ. Bivalent Aptamers Deliver the Punch. Chemistry & Biology. 2008;15(7):644-5. https://doi.org/10.1016/j.chembiol.2008.07.004
  8. Ni X, Castanares M, Mukherjee A, Lupold SE. Nucleic Acid Aptamers: Clinical Applications and Promising New Horizons. Current Medicinal Chemistry 2011;18(27):4206-14. https://doi.org/10.2174/092986711797189600
  9. Zhou J, Rossi JJ. Aptamer-Targeted Cell-Specific RNA Interference. Silence. 2010;1(1):4.
  10. Tang Z, Shangguan D, Wang K, Shi H, Sefah K, Mallikrtchy P, Chen HW, Li Y, Tan W. Selection of aptamers for molecular recognition and characterization of cancer cells. Analytical Chemistry 2007;79:4900-7. https://doi.org/10.1021/ac070189y
  11. Ray P, White RR. Aptamers for targeted drug delivery. Pharmaceuticals 2010;3:1761-78. https://doi.org/10.3390/ph3061761
  12. Shangguan D, Cao Z, Meng L, Mallikaratchy P, Sefah K, Wang H, Li Y, Tan W. Cell-specific aptamer probes for membrane protein elucidation in cancer cells. J Proteome Res 2008;7(5): 2133-39. https://doi.org/10.1021/pr700894d
  13. Luo YL, Shiao YS, Huang YF. Release of photoactivatable drugs from plasmonic nanoparticles for targeted cancer theraphy. ACS NANO 2011;5:7796- 804. https://doi.org/10.1021/nn201592s
  14. Orava EW, Clcmil N, Gariepy J. Delivering cargoes into cancer cells using DNA aptamers targeting internalized surface portals. Biochimica et Biophysica Acta 2010;1798:2190-200. https://doi.org/10.1016/j.bbamem.2010.02.004
  15. Phillips JA, Lopez-Colon D, Zhu Z, Xu Ye, Tan W. Applications of aptamers in cancer cell biology. Analytica Chimica Acta 2008;621:101-8. https://doi.org/10.1016/j.aca.2008.05.031
  16. Mallikaratchy P, Tang Z, Kwame S, Meng Ling, Shangguan D, Tan W. Aptamer directly evolved from live cells recognizes membrane bound immunoglobin heavy mu chain in burkitt's lymphoma cells. Molecular & Cellular Proteomics 2007;6:2230-8.
  17. Jacobson O, Weiss ID, Wang L, Wang Z, Yang X, Dewhurst A, Ma Y, Zhu Guizhi, Niu G, Kiesewetter DO, Vasdew N, Liang SH, Chen X. 18F-Labeled single-stranded DNA aptamer for PET imaging of protein tyrosine kinase-7 expression. J Nucl Med 2015;56(11):1780-5. https://doi.org/10.2967/jnumed.115.160960
  18. Mellor HR, Nolan J, Pickering L, Wormald MR, Platt FM, Dwek RA, Fleet GWJ, Butters TD. Preparation, biochemical characterization and biological properties of radiolabelled N-alkylated deoxynojirimycins. Biochem J 2002;366(Pt 1):225-33. https://doi.org/10.1042/bj20020466
  19. Duangjit S, Pamornpathomkul B, Opanasopit P, Rojanarata T, Obata Y, Takayama K, Ngawhirunpat T. Role of the charge, carbon chain length, and content of surfactant on the skin penetration of meloxicam-loaded liposomes. Int J Nanomedicine 2014;9: 2005-17.
  20. Jeffries B, Wang Z, Troup RI, Goupille A, Questel J-YL, Fallan C, Scott JS, Chiarparin E, Graton J, Linclau B. Lipophilicity trends upon fluorination of isopropyl, cyclopropyl and 3-oxetanyl groups. Beilstein J Org Chem 2002;16 2020;16(1):2141-50.
  21. Victoria C, Maria M . Newton J, Gonzalez J, Fernandez M, Gambini JP, Ibarra M, Chabalogity A, Deutscher S, Quinn T, Cabral P, Cereceoot H. Development of new PTK7 - targeting aptamer-fluorescent and - radiolabelled probes for evaluation as molecular imaging agents: Lymphoma and melanoma in vivo proof of concept. Bioorg Med Chem 2017;25(3):1163-71. https://doi.org/10.1016/j.bmc.2016.12.026
  22. Boswell CA, Sun X, Niu W. Weisman GR, Wong EH, Rheingold AL, Anderson CJ. Comparative in vivo stability of copper-64-labeled cross-bridged and conventional tetraazamacrocyclic complexes. J Med Chem 2004;47:1465-74. https://doi.org/10.1021/jm030383m
  23. Giusto DAD, King GC. Construction, stability, and activity of multivalent circular anticoagulant aptamers. Journal of Biological Chemistry 2004;279(45):46483-9. https://doi.org/10.1074/jbc.M408037200
  24. Huang Y-FH, Shangguan D, Liu H, Phillips JA, Zhang X, Chen Y, Tan W. Molecular assembly of an aptamer-drug conjugate for targeted drug delivery to tumor cells. Chembiochem 2009;10(5):862-8. https://doi.org/10.1002/cbic.200800805
  25. Pieve C, Blackshaw E, Missailidis S, Perkins A. PEGylation and biodistribution of an anti-MUC1 aptamer in MCF-7 tumor-bearing mice. Bioconjug Chem 2012;23(7):1377-81. https://doi.org/10.1021/bc300128r
  26. Li J, Zheng H, Bates PJ, Malik T, Li X-F, Trent JO, Ng CK. Aptamer imaging with Cu-64 labeled AS1411: preliminary assessment in lung cancer. Nucl Med Biol 2014;41(2):179-85.
  27. Jacobson O, Yan X, Niu G, Weiss ID, Ma Y, Szajek LP, Shen B, Kiesewetter DO, Chen X. PET imaging of tenascin-C with a radiolabeled single-stranded DNA aptamer. J Nucl Med 2015;56(4):616-21. https://doi.org/10.2967/jnumed.114.149484