TY - JOUR
T1 - The effect of injected dose on localized tumor accumulation and cardiac uptake of doxorubicin in a Vx2 rabbit tumor model using MR-HIFU mild hyperthermia and thermosensitive liposomes
AU - Cheng, Bingbing
AU - Bing, Chenchen
AU - Staruch, Robert M.
AU - Shaikh, Sumbul
AU - Wodzak Staruch, Michelle
AU - Szczepanski, Debra
AU - Williams, Noelle S.
AU - Laetsch, Theodore W.
AU - Chopra, Rajiv
N1 - Publisher Copyright:
© 2020 The Author(s). Published with license by Taylor & Francis Group, LLC.
PY - 2020/1/1
Y1 - 2020/1/1
N2 - Purpose: When doxorubicin (DOX) is administered via lyso-thermosensitive liposomes (LTLD), mild hyperthermia enhances localized delivery to heated vs. unheated tumors. The optimal LTLD dose and the impact of different doses on systemic drug distribution are unknown. Materials and methods: In this study, we evaluated local and systemic DOX delivery with three LTLD doses (0.1, 0.5, and 2.5 mg/kg) in a Vx2 rabbit tumor model. Temporally and spatially accurate controlled hyperthermia was achieved using a clinical MR-HIFU system for the intended heating duration (40 min). Results: DOX concentration in tissues delivered from LTLD combined with MR-HIFU mild hyperthermia are dose-dependent, including heated/unheated tumor, heart, and other healthy organs. Higher DOX accumulation and tumor-to-heart drug concentration ratio, defined as the ratio of DOX delivered into the tumor vs the heart, were observed in heated tumors compared to unheated tumors in all three tested doses. The DOX uptake efficiency for each mg/kg of LTLD injected IV of heated tumor was significantly higher than that of unheated tumor and heart within the tested dose range (0.1-2.5 mg/kg). The DOX uptake for the heart linearly scaled up as a function of dose while that for the heated tumor showed some evidence of saturation at the high dose of 2.5 mg/kg. Conclusions: These results provide guidance on clinical protocol design of hyperthermia-triggered drug delivery.
AB - Purpose: When doxorubicin (DOX) is administered via lyso-thermosensitive liposomes (LTLD), mild hyperthermia enhances localized delivery to heated vs. unheated tumors. The optimal LTLD dose and the impact of different doses on systemic drug distribution are unknown. Materials and methods: In this study, we evaluated local and systemic DOX delivery with three LTLD doses (0.1, 0.5, and 2.5 mg/kg) in a Vx2 rabbit tumor model. Temporally and spatially accurate controlled hyperthermia was achieved using a clinical MR-HIFU system for the intended heating duration (40 min). Results: DOX concentration in tissues delivered from LTLD combined with MR-HIFU mild hyperthermia are dose-dependent, including heated/unheated tumor, heart, and other healthy organs. Higher DOX accumulation and tumor-to-heart drug concentration ratio, defined as the ratio of DOX delivered into the tumor vs the heart, were observed in heated tumors compared to unheated tumors in all three tested doses. The DOX uptake efficiency for each mg/kg of LTLD injected IV of heated tumor was significantly higher than that of unheated tumor and heart within the tested dose range (0.1-2.5 mg/kg). The DOX uptake for the heart linearly scaled up as a function of dose while that for the heated tumor showed some evidence of saturation at the high dose of 2.5 mg/kg. Conclusions: These results provide guidance on clinical protocol design of hyperthermia-triggered drug delivery.
KW - MR-guided high intensity focused ultrasound
KW - Targeted drug delivery
KW - dose
KW - mild hyperthermia
KW - thermosensitive liposomal doxorubicin
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U2 - 10.1080/02656736.2020.1812737
DO - 10.1080/02656736.2020.1812737
M3 - Article
C2 - 32892667
AN - SCOPUS:85090344530
SN - 0265-6736
VL - 37
SP - 1052
EP - 1059
JO - International Journal of Hyperthermia
JF - International Journal of Hyperthermia
IS - 1
ER -