Thermal combination therapies for local drug delivery by magnetic resonance-guided high-intensity focused ultrasound
| Autor: | Sander Langereis, Ecm Esther Kneepkens, NM Nicole Hijnen, Holger Grüll, Edwin Heijman, Mariska de Smet |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
Hyperthermia
Biodistribution Materials science Focused ultrasound medicine.medical_treatment Ablation 030218 nuclear medicine & medical imaging Polyethylene Glycols 03 medical and health sciences 0302 clinical medicine Drug Delivery Systems Cell Line Tumor Rhabdomyosarcoma medicine Distribution (pharmacology) Animals Doxorubicin Tissue Distribution Tomography Emission-Computed Single-Photon Multidisciplinary Antibiotics Antineoplastic medicine.diagnostic_test Indium Radioisotopes Temperature Hyperthermia Induced medicine.disease Temperature-sensitive liposomes Combined Modality Therapy Magnetic Resonance Imaging High-intensity focused ultrasound Rats PNAS Plus 030220 oncology & carcinogenesis Drug delivery Liposomes High-Intensity Focused Ultrasound Ablation Female Emission computed tomography Biomedical engineering medicine.drug |
| Zdroj: | Proceedings of the National Academy of Sciences of the United States of America (PNAS), 114(24), E4802-E4811. National Academy of Sciences |
| ISSN: | 0027-8424 |
| Popis: | Several thermal-therapy strategies such as thermal ablation, hyperthermia-triggered drug delivery from temperature-sensitive liposomes (TSLs), and combinations of the above were investigated in a rhabdomyosarcoma rat tumor model (n = 113). Magnetic resonance-guided high-intensity focused ultrasound (MR-HIFU) was used as a noninvasive heating device with precise temperature control for image-guided drug delivery. For the latter, TSLs were prepared, coencapsulating doxorubicin (dox) and [Gd(HPDO3A)(H2O)], and injected in tumor-bearing rats before MR-HIFU treatment. Four treatment groups were defined: hyperthermia, ablation, hyperthermia followed by ablation, or no HIFU. The intratumoral TSL and dox distribution were analyzed by single-photon emission computed tomography (SPECT)/computed tomography (CT), autoradiography, and fluorescence microscopy. Dox biodistribution was quantified and compared with that of nonliposomal dox. Finally, the treatment efficacy of all heating strategies plus additional control groups (saline, free dox, and Caelyx) was assessed by tumor growth measurements. All HIFU heating strategies combined with TSLs resulted in cellular uptake of dox deep into the interstitial space and a significant increase of tumor drug concentrations compared with a treatment with free dox. Ablation after TSL injection showed [Gd(HPDO3A)(H2O)] and dox release along the tumor rim, mirroring the TSL distribution pattern. Hyperthermia either as standalone treatment or before ablation ensured homogeneous TSL, [Gd(HPDO3A)(H2O)], and dox delivery across the tumor. The combination of hyperthermia-triggered drug delivery followed by ablation showed the best therapeutic outcome compared with all other treatment groups due to direct induction of thermal necrosis in the tumor core and efficient drug delivery to the tumor rim. |
| Databáze: | OpenAIRE |
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