Targeted Tumor Therapy with Radiolabeled DNA Intercalator: A Possibility? Preclinical Investigations with 177Lu-Acridine.

Item request has been placed! ×
Item request cannot be made. ×
loading   Processing Request
  • Additional Information
    • Affiliation:
      Mumbai-, Radiopharmaceuticals Division, Bhabha Atomic Research Centre, Trombay, Mumbai-400085, India
      Mumbai-, Homi Bhabha National Institute, Anushaktinagar, Mumbai-400094, India
      Mumbai-, Radiation Biology and Health Sciences Division, Bhabha Atomic Research Centre, Trombay, Mumbai-400085, India
    • Subject Terms:
    • Subject Terms:
    • Abstract:
      Objective. A DNA intercalating agent reversibly stacks between the adjacent base pairs of DNA and thus is expected to exhibit preferential localization in the tumorous lesions as tumors are associated with enhanced DNA replication. Therefore, radiolabeled DNA intercalators are supposed to have potential to be used in targeted tumor therapy. Working in this direction, an attempt was made to radiolabel 9-aminoacridine, a DNA intercalator, with 177Lu, one of the most useful therapeutic radionuclides, and study the potential of 177Lu-acridine in targeted tumor therapy. Experiments. 9-Aminoacridine was coupled with p-NCS-benzyl-DOTA to facilitate radiolabeling, and the conjugate was radiolabeled with 177Lu. Different reaction parameters were optimized in order to obtain 177Lu-acridine complex with maximum radiochemical purity. In vitro stability of the radiolabeled complex was studied in normal saline and human blood serum. Biological behavior of the radiolabeled agent was studied both in vitro and in vivo using the Raji cell line and fibrosarcoma tumor-bearing Swiss mice, respectively. Results. 177Lu-acridine complex was obtained with ~100% radiochemical purity under the optimized reaction conditions involving incubation of 1.5 mg/mL of ligand with 177Lu (1 mCi, 37 MBq) at 100°C at pH ~5 for 45 minutes. The complex maintained a radiochemical purity of >85% in saline at 6 d and >70% in human serum at 2 d postpreparation. In vitro cellular study showed uptake of the radiotracer (5.3 ± 0.13 %) in the Raji cells along with significant cytotoxicity (78.06 ± 2.31 % after 6 d). Biodistribution study revealed considerable accumulation of the radiotracer in tumor 9.98 ± 0.13 % ID / g within 1 h postadministration and retention therein till 6 d postadministration 4.00 ± 0.16 % ID / g with encouraging tumor to nontarget organ uptake ratios. Conclusions. The present study, although preliminary, indicates the potential of 177Lu-acridine and thus radiolabeled DNA intercalators in targeted tumor therapy. However, further detailed evaluation is required to explore the actual potential of such agents in targeted tumor therapy.
    • Journal Subset:
      Biomedical; Peer Reviewed; USA
    • ISSN:
      2314-6133
    • MEDLINE Info:
      NLM UID: 101600173
    • Publication Date:
      20200729
    • Publication Date:
      20200729
    • DOI:
      10.1155/2020/9514357
    • Accession Number:
      144773668
  • Citations
    • ABNT:
      GHOSH, S. et al. Targeted Tumor Therapy with Radiolabeled DNA Intercalator: A Possibility? Preclinical Investigations with 177Lu-Acridine. BioMed Research International, [s. l.], p. 1–13, 2020. DOI 10.1155/2020/9514357. Disponível em: http://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=rzh&AN=144773668. Acesso em: 24 out. 2020.
    • AMA:
      Ghosh S, Das T, Suman SK, Kumar C, Sarma HD, Dash A. Targeted Tumor Therapy with Radiolabeled DNA Intercalator: A Possibility? Preclinical Investigations with 177Lu-Acridine. BioMed Research International. July 2020:1-13. doi:10.1155/2020/9514357
    • APA:
      Ghosh, S., Das, T., Suman, S. K., Kumar, C., Sarma, H. D., & Dash, A. (2020). Targeted Tumor Therapy with Radiolabeled DNA Intercalator: A Possibility? Preclinical Investigations with 177Lu-Acridine. BioMed Research International, 1–13. https://doi.org/10.1155/2020/9514357
    • Chicago/Turabian: Author-Date:
      Ghosh, Subhajit, Tapas Das, Shishu K. Suman, Chandan Kumar, Haladhar D. Sarma, and Ashutosh Dash. 2020. “Targeted Tumor Therapy with Radiolabeled DNA Intercalator: A Possibility? Preclinical Investigations with 177Lu-Acridine.” BioMed Research International, July, 1–13. doi:10.1155/2020/9514357.
    • Harvard:
      Ghosh, S. et al. (2020) ‘Targeted Tumor Therapy with Radiolabeled DNA Intercalator: A Possibility? Preclinical Investigations with 177Lu-Acridine’, BioMed Research International, pp. 1–13. doi: 10.1155/2020/9514357.
    • Harvard: Australian:
      Ghosh, S, Das, T, Suman, SK, Kumar, C, Sarma, HD & Dash, A 2020, ‘Targeted Tumor Therapy with Radiolabeled DNA Intercalator: A Possibility? Preclinical Investigations with 177Lu-Acridine’, BioMed Research International, pp. 1–13, viewed 24 October 2020, .
    • MLA:
      Ghosh, Subhajit, et al. “Targeted Tumor Therapy with Radiolabeled DNA Intercalator: A Possibility? Preclinical Investigations with 177Lu-Acridine.” BioMed Research International, July 2020, pp. 1–13. EBSCOhost, doi:10.1155/2020/9514357.
    • Chicago/Turabian: Humanities:
      Ghosh, Subhajit, Tapas Das, Shishu K. Suman, Chandan Kumar, Haladhar D. Sarma, and Ashutosh Dash. “Targeted Tumor Therapy with Radiolabeled DNA Intercalator: A Possibility? Preclinical Investigations with 177Lu-Acridine.” BioMed Research International, July 25, 2020, 1–13. doi:10.1155/2020/9514357.
    • Vancouver/ICMJE:
      Ghosh S, Das T, Suman SK, Kumar C, Sarma HD, Dash A. Targeted Tumor Therapy with Radiolabeled DNA Intercalator: A Possibility? Preclinical Investigations with 177Lu-Acridine. BioMed Research International [Internet]. 2020 Jul 25 [cited 2020 Oct 24];1–13. Available from: http://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=rzh&AN=144773668