Biomedical Engineering Reference
In-Depth Information
7.6.1 NMs Contrast Agents in Clinical Use
There are two intravenous formulations of SPIONs in clinical use and one
formulation has been approved for oral use
3
(
Table 7.2
). The first NMs to be
clinically approved for in vivo imaging are the SPIONs.
3
The first clinically
available brand is Feridex I.V.
®
(ferumoxides injectable solution) which was
introduced as the world's first organ specific MR contrast agent in 1996.
3
It was
followed by Resovist
®
(ferucarbotran injectable solution) that was approved in
the European Union (EU), Australia, and Japan for the detection and evaluation
liver lesions using MRI.
3
Resovist consists of 80 nm particles while Feridex is
about 50-180 nm.
239
These two iron-based NMs, Feridex I.V.
®
and Resovist
®
,
have iron content that produces strong local disruptions in the magnetic field of
MRI scanners, causing an increased
T
2* relaxation and decreased signal inten-
sity in the areas where the NMs accumulate.
3
As a result, they are considered
“negative” contrast agents. Both of these contrast agents rely on passive tar-
geting strategies to detect alterations in the RES, making normal liver, spleen,
bone marrow, and lymph nodes appear dark.
3
Processes that reduce the uptake
of SPIONs such as inflammation, scarring, and most focal lesions of the liver
produce localized regions of signal.
240
In comparison with other heavy metals
that are harmful, the key advantage of SPIONs as MRI contrast agents is their
ability to integrate physiologically as the iron and iron oxides are metabolized,
stored in intracellular pools as ferritin, and incorporated into hemoglobin.
3
In
rodent models, dose escalation studies using a dose well above that used for
MRI procedures (<5 mg/kg) showed no identifiable side effects even at 100 mg
iron/kg.
241
The iron NMs, based on radiotracer and histological studies in
rodents, becomes part of the body iron pool, first accumulating in the RES
and then slowly disappearing over the course of 14-28 days.
242,243
Intravenous
administration of semisynthetic carbohydrates coated IO NMs was found to
safely increase mean blood hemoglobin concentrations by about 1.0 g/dL over a
35 day period in humans.
244
Based on these studies, in June 2009, Feraheme™
TABLE 7.2 Clinically Approved Nanomaterials
Brand/Name
Composition
Size
Use
Feridex™
Dextran coated
SPIO
50-180 nm
MRI Contrast
Resovist™
Carboxydextran
coated SPIO
80 nm
MRI Contrast
Feraheme™
Polyglucose
sorbitol Carboxy-
methylether coated
SPIO
17-31 nm
Iron deficiency
anemia
