γ-tocotrienol-loaded liposomes for radioprotection from hematopoietic side effects caused by radiotherapeutic drugs Journal Article

   


Authors: Lee, S. G.; Kalidindi, T. M.; Lou, H.; Gangangari, K.; Punzalan, B.; Bitton, A.; Lee, C. J.; Vargas, H. A.; Park, S.; Bodei, L.; Kharas, M. G.; Singh, V. K.; Pillarsetty, N. V. K.; Larson, S. M.
Article Title: γ-tocotrienol-loaded liposomes for radioprotection from hematopoietic side effects caused by radiotherapeutic drugs
Abstract: With the successful development and increased use of targeted radionuclide therapy for treating cancer comes the increased risk of radiation injury to bone marrow-both direct suppression and stochastic effects, leading to neoplasia. Herein, we report a novel radioprotector drug, a liposomal formulation of γ-tocotrienol (GT3), or GT3-Nano for short, to mitigate bone marrow radiation damage during targeted radionuclide therapy. Methods: GT3 was loaded into liposomes using passive loading. 64Cu-GT3-Nano and 3H-GT3-Nano were synthesized to study the in vivo biodistribution profile of the liposome and GT3 individually. The radioprotection efficacy of GT3-Nano was assessed after acute 137Cs whole-body irradiation at a sublethal (4 Gy), a lethal (9 Gy), or a single high-dose administration of 153Sm-ethylenediamine-N,N,N',N'-tetrakis(methylene phosphonic acid) (EDTMP). Flow cytometry and fluorescence microscopy were used to analyze hematopoietic cell population dynamics and the cellular site of GT3-Nano localization in the spleen and bone marrow, respectively. Results: Bone marrow uptake and retention (percentage injected dose per gram of tissue) at 24 h was 6.98 ± 2.34 for 64Cu-GT3-Nano and 7.44 ± 2.52 for 3H-GT3-Nano. GT3-Nano administered 24 h before or after 4 Gy of total-body irradiation (TBI) promoted rapid and complete hematopoietic recovery, whereas recovery of controls stalled at 60%. GT3-Nano demonstrated dose-dependent radioprotection, achieving 90% survival at 50 mg/kg against lethal 9-Gy TBI. Flow cytometry of the bone marrow indicated that progenitor bone marrow cells MPP2 and CMP were upregulated in GT3-Nano-treated mice. Immunohistochemistry showed that GT3-Nano accumulates in CD105-positive sinusoid epithelial cells. Conclusion: GT3-Nano is highly effective in mitigating the marrow-suppressive effects of sublethal and lethal TBI in mice. GT3-Nano can facilitate rapid recovery of hematopoietic components in mice treated with the endoradiotherapeutic agent 153Sm-EDTMP. © 2021 by the Society of Nuclear Medicine and Molecular Imaging.
Keywords: bone marrow; liposome; radiation protection; γ-tocotrienol
Journal Title: Journal of Nuclear Medicine
Volume: 62
Issue: 4
ISSN: 0161-5505
Publisher: Society of Nuclear Medicine  
Date Published: 2021-04-01
Start Page: 584
End Page: 590
Language: English
DOI: 10.2967/jnumed.120.244681
PUBMED: 32826318
PROVIDER: scopus
PMCID: PMC8049360
DOI/URL:

https://www.scopus.com/inward/record.uri?eid=2-s2.0-85103682249&doi=10.2967%2fjnumed.120.244681&partnerID=40&md5=dff287c9b6a77ff8e8516afdb4a0f906
Notes: Article -- MSK author Hanzhi Luo's last name is misspelled on the original publication -- Export Date: 3 May 2021 -- Source: Scopus
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MSK Authors
  1. Nagavarakishore Pillarsetty
    132 Pillarsetty
  2. Hebert Alberto Vargas Alvarez
    267 Vargas Alvarez
  3. Steven M Larson
    958 Larson
  4. Blesida Punzalan
    38 Punzalan
  5. Michael Kharas
    96 Kharas
  6. Sang Gyu Lee
    20 Lee
  7. Teja Muralidhar Kalidindi
    38 Kalidindi
  8. Kishore Kumar Gangangari
    11 Gangangari
  9. Lisa Bodei
    205 Bodei
  10. Hanzhi Luo
    22 Luo
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