Publications [#210124] of Mark W. Dewhirst

Papers Published

1. AH Negussie, PS Yarmolenko, A Partanen, A Ranjan, G Jacobs, D Woods, H Bryant, D Thomasson, MW Dewhirst, BJ Wood, MR Dreher, Formulation and characterisation of magnetic resonance imageable thermally sensitive liposomes for use with magnetic resonance-guided high intensity focused ultrasound., International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group, vol. 27 no. 2 (2011), pp. 140-55, ISSN 1464-5157 [doi]
   (last updated on 2012/10/26)

   Abstract:
   OBJECTIVE: Objectives of this study were to: 1) develop iLTSL, a low temperature sensitive liposome co-loaded with an MRI contrast agent (ProHance® Gd-HP-DO3A) and doxorubicin, 2) characterise doxorubicin and Gd-HP-DO3A release from iLTSL and 3) investigate the ability of magnetic resonance-guided high intensity focused ultrasound (MR-HIFU) to induce and monitor iLTSL content release in phantoms and in vivo. METHODS: iLTSL was passively loaded with Gd-HP-DO3A and actively loaded with doxorubicin. Doxorubicin and Gd-HP-DO3A release was quantified by fluorescence and spectroscopic techniques, respectively. Release with MR-HIFU was examined in tissue-mimicking phantoms containing iLTSL and in a VX2 rabbit tumour model. RESULTS: iLTSL demonstrated consistent size and doxorubicin release kinetics after storage at 4°C for 7 days. Release of doxorubicin and Gd-HP-DO3A from iLTSL was minimal at 37°C but fast when heated to 41.3°C. The magnitude of release was not significantly different between doxorubicin and Gd-HP-DO3A over 10 min in HEPES buffer and plasma at 37°, 40° and 41.3°C (p > 0.05). Relaxivity of iLTSL increased significantly (p < 0.0001) from 1.95 ± 0.05 to 4.01 ± 0.1 mMs⁻¹ when heated above the transition temperature. Signal increase corresponded spatially and temporally to MR-HIFU-heated locations in phantoms. Signal increase was also observed in vivo after iLTSL injection and after each 10-min heating (41°C), with greatest increase in the heated tumour region. CONCLUSIONS: An MR imageable liposome formulation co-loaded with doxorubicin and an MR contrast agent was developed. Stability, imageability, and MR-HIFU monitoring and control of content release suggest that MR-HIFU combined with iLTSL may enable real-time monitoring and spatial control of content release.

   Keywords:
   Animals • Contrast Media • Doxorubicin • Gadolinium • Heterocyclic Compounds • Humans • Kinetics • Liposomes • Magnetic Resonance Imaging • Magnetic Resonance Imaging, Interventional • Organometallic Compounds • Phantoms, Imaging • Rabbits • Ultrasonography, Interventional • administration & dosage • administration & dosage* • diagnostic use • diagnostic use* • methods