Comparison of two superparamagnetic viral-sized iron oxide particles ferumoxides and ferumoxtran-10 with a gadolinium chelate in imaging intracranial tumors.
OBJECTIVE
Ultrasmall superparamagnetic iron oxide particles result in shortening of T1 and T2 relaxation time constants and can be used as MR contrast agents. We tested four hypotheses by evaluating MR images of intracranial tumors after infusion of two iron oxide agents in comparison with a gadolinium chelate: 1) Ferumoxtran in contrast to ferumoxides can be used as an intravenous MR contrast agent in intracranial tumors; 2) ferumoxtran enhancement, albeit delayed, is similar to gadolinium enhancement; 3) ferumoxtran-enhanced MR images in contrast to gadolinium-enhanced MR images may be compared with histologic specimens showing the cellular location of iron oxide particles; 4) ferumoxtran can serve as a model for viral vector delivery.


METHODS
In 20 patients, ferumoxides and ferumoxtran were intravenously administered at recommended clinical doses. MR imaging was performed 30 minutes and 4 hours after ferumoxides infusion (n = 3), whereas ferumoxtran-enhanced MR imaging (n = 17) was performed 6 and 24 hours after infusion in the first five patients and 24 hours after infusion in the remaining 12. MR sequences were spin-echo (SE) T1-weighted, fast SE T2- and proton density-weighted, gradient-recalled-echo T2*-weighted, and, in four cases, echo-planar T2-weighted sequences. Representative regions of interest were chosen on pre- and postcontrast images to compare each sequence and signal intensity.


RESULTS
Despite some degree of gadolinium enhancement in all tumors, no significant T1 or T2 signal intensity changes were seen after ferumoxides administration at either examination time. Fifteen of 17 patients given ferumoxtrans had T1 and/or T2 shortening consistent with iron penetration into tumor. Histologic examination revealed minimal iron staining of the tumor with strong staining at the periphery of the tumors.


CONCLUSIONS
1) Ferumoxtran can be used as an intravenous MR contrast agent in intracranial tumors, mostly malignant tumors. 2) Enhancement with ferumoxtran is comparable to but more variable than that with the gadolinium chelate. 3) Histologic examination showed a distribution of ferumoxtran particles similar to that on MR images, but at histology the cellular uptake was primarily by parenchymal cells at the tumor margin. 4) Ferumoxtran may be used as a model for viral vector delivery in malignant brain tumors.
Varallyay
Peter
P
Department of Neurology, Oregon Health and Science University, Portland, Oregon 97201, USA.
Nesbit
Gary
G
Muldoon
Leslie L
LL
Nixon
Randal R
RR
Delashaw
Johnny
J
Cohen
James I
JI
Petrillo
Annie
A
Rink
Doris
D
Neuwelt
Edward A
EA
D000328:Adult; D000368:Aged; D001932:Brain Neoplasms / Q000175:diagnosis* / Q000628:therapy; D003287:Contrast Media / Q000008:administration & dosage; D003911:Dextrans; D005260:Female; D052203:Ferrosoferric Oxide; D019786:Gadolinium DTPA; D005822:Genetic Vectors; D006801:Humans; D007275:Injections, Intravenous; D007501:Iron; D008279:Magnetic Resonance Imaging; D058185:Magnetite Nanoparticles; D008297:Male; D008875:Middle Aged; D010087:Oxides; D010316:Particle Size; D014780:Viruses
D003287:Contrast Media; D003911:Dextrans; D058185:Magnetite Nanoparticles; D010087:Oxides; C097921:ferumoxtran-10; C064925:gadodiamide; D007501:Iron; C065507:ferumoxides; D019786:Gadolinium DTPA; D052203:Ferrosoferric Oxide