Magnetic resonance imaging of temperature-sensitive liposome release: drug dose painting and antitumor effects
- PMID: 17202113
- DOI: 10.1093/jnci/djk005
Magnetic resonance imaging of temperature-sensitive liposome release: drug dose painting and antitumor effects
Abstract
Background: In preclinical studies, lysolipid-based temperature-sensitive liposomes (LTSLs) containing chemotherapy drugs administered in combination with local hyperthermia have been found to increase tumor drug concentrations and improve antitumor efficacy of the drugs. We used a novel magnetic resonance imaging (MRI) method to measure the temporal and spatial patterns of drug delivery in a rat fibrosarcoma model during treatment with LTSLs containing doxorubicin and an MRI contrast agent (manganese) (Dox/Mn-LTSLs) administered at different times with respect to hyperthermia.
Methods: Rats bearing 10- to 12-mm fibrosarcomas (n = 6-7 per group) were treated with Dox/Mn-LTSLs (at a dose of 5 mg doxorubicin/kg body weight) before and/or during 60 minutes of local tumor hyperthermia administered via a catheter inserted at the center of the tumor. Drug distribution was monitored continuously via MRI. Magnetic resonance changes were used to calculate intratumoral doxorubicin concentrations throughout treatment. Tumors were monitored until they reached five times their volume on the day of treatment or 60 days. Doxorubicin concentrations and times for tumors to reach five times their volume on the day of treatment were analyzed using the Kruskal-Wallis test and the Kaplan-Meier product-limit method, respectively. All statistical tests were two-sided.
Results: Administration of Dox/Mn-LTSLs before, during, and both before and during hyperthermia yielded central, peripheral, and uniform drug distributions, respectively. Doxorubicin accumulated more quickly and reached higher concentrations in the tumor when Dox/Mn-LTSLs were administered during hyperthermia than when administered before hyperthermia (rate: 9.8 versus 1.8 microg/min, difference = 8.0 microg/min, 95% confidence interval [CI] = 6.8 to 12.8 microg/min, P = .003; concentration: 15.1 versus 8.0 ng/mg, difference = 7.1 ng/mg, 95% CI = 3.6 to 10.6 ng/mg, P = .028). LTSL administered during hyperthermia also yielded the greatest antitumor effect, with a median time for tumors to reach five times their volume on the day of treatment of 34 days (95% CI = 30 days to infinity) compared with 18.5 days (95% CI = 16 to 23 days) for LTSL before hyperthermia and 22.5 days (95% CI = 15 to 25 days) for LTSL before and during hyperthermia.
Conclusions: In this rat fibrosarcoma model, LTSLs were most effective when delivered during hyperthermia, which resulted in a peripheral drug distribution.
Similar articles
-
Efficacy of liposomes and hyperthermia in a human tumor xenograft model: importance of triggered drug release.Cancer Res. 2000 Dec 15;60(24):6950-7. Cancer Res. 2000. PMID: 11156395
-
A tracer dose of technetium-99m-labeled liposomes can estimate the effect of hyperthermia on intratumoral doxil extravasation.Clin Cancer Res. 2006 Nov 15;12(22):6800-7. doi: 10.1158/1078-0432.CCR-06-0839. Clin Cancer Res. 2006. PMID: 17121901
-
Synthesis and characterisation of ultrasound imageable heat-sensitive liposomes for HIFU therapy.Int J Hyperthermia. 2015;31(6):674-85. doi: 10.3109/02656736.2015.1057622. Epub 2015 Jul 17. Int J Hyperthermia. 2015. PMID: 26185910 Free PMC article.
-
Final report on the safety assessment of capsicum annuum extract, capsicum annuum fruit extract, capsicum annuum resin, capsicum annuum fruit powder, capsicum frutescens fruit, capsicum frutescens fruit extract, capsicum frutescens resin, and capsaicin.Int J Toxicol. 2007;26 Suppl 1:3-106. doi: 10.1080/10915810601163939. Int J Toxicol. 2007. PMID: 17365137 Review.
-
Antivascular and antitumor activities of liposome-associated drugs.Anticancer Res. 2004 Mar-Apr;24(2A):397-404. Anticancer Res. 2004. PMID: 15152936 Review.
Cited by
-
Lipid-based nanosystems: the next generation of cancer immune therapy.J Hematol Oncol. 2024 Jul 19;17(1):53. doi: 10.1186/s13045-024-01574-1. J Hematol Oncol. 2024. PMID: 39030582 Free PMC article. Review.
-
Emerging biomedical imaging-based companion diagnostics for precision medicine.iScience. 2023 Jul 3;26(8):107277. doi: 10.1016/j.isci.2023.107277. eCollection 2023 Aug 18. iScience. 2023. PMID: 37520706 Free PMC article. Review.
-
Recent Preclinical and Clinical Progress in Liposomal Doxorubicin.Pharmaceutics. 2023 Mar 9;15(3):893. doi: 10.3390/pharmaceutics15030893. Pharmaceutics. 2023. PMID: 36986754 Free PMC article. Review.
-
Review of the Delivery Kinetics of Thermosensitive Liposomes.Cancers (Basel). 2023 Jan 7;15(2):398. doi: 10.3390/cancers15020398. Cancers (Basel). 2023. PMID: 36672347 Free PMC article. Review.
-
Chemotherapeutic nanomaterials in tumor boundary delineation: Prospects for effective tumor treatment.Acta Pharm Sin B. 2022 Jun;12(6):2640-2657. doi: 10.1016/j.apsb.2022.02.016. Epub 2022 Feb 23. Acta Pharm Sin B. 2022. PMID: 35755279 Free PMC article. Review.
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical