Artikel
Experiences with ferumoxtran-10, an iron-oxide nanoparticle as contrast material in imaging of brain tumors
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Autoren
Veröffentlicht: | 23. April 2004 |
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Gliederung
Text
Objective
Ultra small superparamagnetic iron oxide particles (USPIO) result in shortening of T1 and T2 relaxation time constants an can be used as MR contrast medium. We evaluated the potential use of ferumoxtran-10 iron oxide nanoparticles (Combidex®, Sinerem™) in imaging of brain tumors in comparison to the conventional gadolinium enhanced MRI. Since the particles do accumulate in most of the investigated tumors, specimens stained for iron were histologically evaluated and directly compared to imaging findings. Ferumoxtran-10 was tested in intraoperative imaging using low-field MRI. Due to the long plasma half life of the-particles we tried to asses residual tumor in early postoperative imaging.
Methods
32 patients with different intracranial tumors underwent gadolinium and ferumoxtran-10 enhanced imaging. All tumors were histologically verified either by a previous neurosurgical intervention or after the current surgery. Seven of these patients harboring malignant brain tumors underwent pre- and postoperative MR imaging both with gadolinium and ferumoxtran-10. Two patients underwent introperative imaging using 0.15 T introperative MR unit. Ferumoxtran-10 was administered as a 30 minutes intravenous infusion at a dose of 2.6mg Fe/kg 24 hours before imaging. Removed specimens were stained for iron using DAB enhanced Perl's stain.
Results
29 of the 32 gadolinium-enhancing tumors showed T1 and/or T2 shortening with ferumoxtran-10 consistent with iron oxide penetration into tumor. The enhancement pattern of ferumoxtran-10 was similar to that of gadolinium, however in 4 patients MRI showed areas enhanced with ferumoxtran-10 but not with gadolinium. In one case available for follow-up, gadolinium enhancement developed and progressed in these areas. In both intra-operative imaging cases enhancement caused by previously infused ferumoxtran-10 was detectable by low-field MRI. Comparison of the pre- and postoperative MR revealed residual ferumoxtran-10 enhancing areas in four of seven cases. Histology revealed minimal iron staining of the dense tumor with strong staining of the tumor margin.
Conclusions
Ferumoxtran-10 enhancement is comparable to that with gadolinium and can be used as an intravenous MR contrast agent in imaging of intracranial tumors. Ferumoxtran-10 accumulation can be detected histologically and distribution of the iron is similar to that on MR images. Ferumoxtran-10 enhanced MRI showed additional lesions not seen with gadolinium, resulting improved imaging of the multifocal nature of malignant gliomas. Enhancement caused by ferumoxtran-10 appears even on low-field introperative MRI. Residual ferumoxtran-10-enhancing lesions have persistent increased T1 signal intensity, rendering the potential to evaluate residual tumor without re-administering a contrast material. Thus ferumoxtran-10 may be used as a single dose contrast agent for pre-, intra- and postoperative imaging of brain tumors.