Feasibility of Using Hyperosmolar Mannitol as a Liquid Tumor Embolization Agent
Lei Fenga,
Beverly A. Kienitzc,
Carolyn Matsumotoa,
Jeffrey Bruceb,
Michael Sistib,
Hoang Duongd and
John Pile-Spellmana
a Department of Radiology, Columbia University, New York, NY
b Department of Neurosurgery, Columbia University, New York, NY
c Departments of Radiology and Neurological Surgery, University of Wisconsin, Madison, WI
d Department of Radiology, Hollywood Hospital, Hollywood, FL
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FIG 1. Cytotoxicity of mannitol on endothelial and meningioma cells.
A, HUVECs stained with LIVE/DEAD kit. After treatment with 1200 mOsm for 15 minutes, almost all endothelial cells shrank and lost their typical cobblestone morphology. Many of them detached from the culture plate. Orange nuclei depicting dead cells can be seen on the remaining cells.
B, Meningioma cells stained with LIVE/DEAD kit. Similar cytotoxic effect is seen in the meningioma culture after incubation with 600 mOsm for 1 hour.
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FIG 2. Dose- and time-dependent cytotoxic effect of mannitol on endothelial cells. The kill rates of endothelial cells by various concentrations of mannitol after 15- (white bars) and 30-minute (gray or hatched bars) incubation are shown in this graph. NS, normal saline; M300, 300 mOsm mannitol; M600, 600 mOsm mannitol; M900, 900 mOSm mannitol; M1200, 1200 mOsm mannitol; M/I, 25% mannitol and iohexol mixed at 2 : 1 ratio; I, iohexol alone. A small portion of cell death (8–10 ± 1%) is caused by <900 mOsm mannitol after 15 minutes of incubation. As much as 17 ± 2% of endothelial cells die after 15 minutes of incubation with 1200 mOsm mannitol. When incubated for 30 minutes, the cell death rates are significantly higher for all concentrations of mannitol (P < .01 by t test). Mannitol and iohexol mixture has the highest cell death rate, at 52 ± 1%. Normal saline and iohexol alone have little effect on survival of endothelial cells. The error bars depict standard errors.
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FIG 3. Cytotoxic effect of mannitol on five meningioma cell lines. The average kill rates of five meningioma cell lines by 300 mOsm (M300) of mannitol, 600 mOsm (M600), of mannitol and mannitol/iohexol 2:1 mixture (M/I) are shown in this graph. The cell death rates are 22 ± 2% and 23 ± 3% for 600 mOsm of mannitol and mannitol and iohexol mixture, respectively. Little cytotoxic effect is seen for normalsaline (NS) and iohexol alone (I).
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FIG 4. Apoptotic and lytic cell death in meningioma cells. After 1-hour treatment of meningioma cell lines with 900 mOsm of mannitol (A and B), normal saline (C), and 900 mOsm hypertonic saline (D), the cells are reacted with TUNEL reagents to detect programmed cell death. A rapidly proliferating meningioma cell line (A) demonstrates frequent apoptotic cells that are stained brown by the TUNEL reagents. There are very few ghosts of dissolved cells, which are marked by the arrows. More lytic (arrows) cell death than apoptotic cell death (brown cells) occurs in a slow-growing meningioma line (B). Normal saline and hypertonic saline controls reveal no significant cell death.
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FIG 5. Mannitol embolization of a large frontal meningioma.
A, Tumor vessels coming off the left middle meningeal artery are shown by this early arterial phase of left external carotid angiogram.
B, The capillary phase of the same angiogram reveals the typical tumor blush in the meningioma.
C, Postembolization angiogram of the left external carotid artery shows lack of filling of the tumor vessels in the early arterial phase.
D, Most of the tumor blush has been eliminated and contrast stagnation is seen in one of the middle meningeal branch in the delayed phase.
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FIG 6. MR imaging changes after embolization.
A, Before embolization, T1-weighted axial image of the brain with gadolinium reveals a large left parietal extraaxial homogenously enhancing tumor, consistent with meningioma.
B, T2-weighted axial image demonstrating significant mass effect and parenchymal edema.
C, After embolization, only the periphery of the tumor shows enhancement on this postcontrast T1 axial image. The center of the tumor becomes necrotic.
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