362
T. Vemulkar and R. P. Cowburn
15.3 Case Studies
15.3.1 Exploring the Potential of MPI In Vivo for the First
Time
The first in vivo demonstration of MPI [130] as an imaging modality for cancer
detection is of great interest to the field of nanoparticle magnetism. With potential as
a high resolution, high sensitivity, safe, and cheap medical imaging technique, MPI
is expected to be a field of both commercial and research interest in the biomedical
space in the coming decade. The technique is presently capable of imaging ngs of Fe
tracer in the form of SPIONs which can correspond to volume of a few hundred cells
[131]. Since there is no signal attenuation, and no signal from surrounding tissue,
the extremely high contrast technique allows for the visualization of tissue perfusion
with resolution potentially down to hundreds of microns [130].
This in vivo study imaged a new SPION-based tracer injected into rats bearing
breast cancer tumours. The biodistribution of the tracer was tracked over 6 days
providing excellent insight into the behaviour of the tracer for MPI, as well as
highlighting the strengths of the technique very effectively.
The LS-008 SPION formulation used for this study was developed by Lodespin Labs has been optimized in other work [132]. The nanoparticles consist of
monodisperse oleic acid capped SPION cores around 25 nm that are then coated
with poly(maleic anhydride-alt-1-octadecene) (PMAO)—polyethylene glycol (PEG)
polymer chains for colloidal stability. This formulation was found to be stable
in the high salt concentrations that are found physiologically and that often drive
nanoparticle aggregation and impair colloidal stability.
The six-day evolution of the biodistribution of the tracer was tracked with MPI
in tumour bearing rats. Seven athymic nude rats were prepared with subcutaneous
implantation of breast cancer tumours. The tracer was intravenously injected in the
tail 4 weeks after the tumour implantation. Three groups were prepared for the
experiment. Group A was a high dose group at 15 mg/kg, group B was a low dose
group at 5 mg/kg, and the control group C received no tumour and the high dose. No
biofunctionalization was used to target the tumour, but instead the study relied on
the fact that tumours preferentially accumulate nanoparticles because of their leakier
vasculature than regular tissue, known as the enhanced permeability and retention
(EPR) effect [133]. In fact, the study could directly observe the EPR effect and the
dynamics of the tracer accumulation in the tumour. An initial enhancement in signal
was observed at the edges of the tumour, followed by accumulation, and then the
tracer was cleared over the course of 4–6 days (Fig. 15.5).
The quantitative nature of MPI (via a calibration sample) meant that the study
could track the amount of tracer in the various organs over time. The pharmacokinetics of the tracer was modelled by a two-compartment method, the blood pool
and the tumour. The model fits the experimental results for both the high dose and
low-dose group which allowed tracer distribution to be quantified directly from the
MPI signal intensity.
T. Vemulkar and R. P. Cowburn
15.3 Case Studies
15.3.1 Exploring the Potential of MPI In Vivo for the First
Time
The first in vivo demonstration of MPI [130] as an imaging modality for cancer
detection is of great interest to the field of nanoparticle magnetism. With potential as
a high resolution, high sensitivity, safe, and cheap medical imaging technique, MPI
is expected to be a field of both commercial and research interest in the biomedical
space in the coming decade. The technique is presently capable of imaging ngs of Fe
tracer in the form of SPIONs which can correspond to volume of a few hundred cells
[131]. Since there is no signal attenuation, and no signal from surrounding tissue,
the extremely high contrast technique allows for the visualization of tissue perfusion
with resolution potentially down to hundreds of microns [130].
This in vivo study imaged a new SPION-based tracer injected into rats bearing
breast cancer tumours. The biodistribution of the tracer was tracked over 6 days
providing excellent insight into the behaviour of the tracer for MPI, as well as
highlighting the strengths of the technique very effectively.
The LS-008 SPION formulation used for this study was developed by Lodespin Labs has been optimized in other work [132]. The nanoparticles consist of
monodisperse oleic acid capped SPION cores around 25 nm that are then coated
with poly(maleic anhydride-alt-1-octadecene) (PMAO)—polyethylene glycol (PEG)
polymer chains for colloidal stability. This formulation was found to be stable
in the high salt concentrations that are found physiologically and that often drive
nanoparticle aggregation and impair colloidal stability.
The six-day evolution of the biodistribution of the tracer was tracked with MPI
in tumour bearing rats. Seven athymic nude rats were prepared with subcutaneous
implantation of breast cancer tumours. The tracer was intravenously injected in the
tail 4 weeks after the tumour implantation. Three groups were prepared for the
experiment. Group A was a high dose group at 15 mg/kg, group B was a low dose
group at 5 mg/kg, and the control group C received no tumour and the high dose. No
biofunctionalization was used to target the tumour, but instead the study relied on
the fact that tumours preferentially accumulate nanoparticles because of their leakier
vasculature than regular tissue, known as the enhanced permeability and retention
(EPR) effect [133]. In fact, the study could directly observe the EPR effect and the
dynamics of the tracer accumulation in the tumour. An initial enhancement in signal
was observed at the edges of the tumour, followed by accumulation, and then the
tracer was cleared over the course of 4–6 days (Fig. 15.5).
The quantitative nature of MPI (via a calibration sample) meant that the study
could track the amount of tracer in the various organs over time. The pharmacokinetics of the tracer was modelled by a two-compartment method, the blood pool
and the tumour. The model fits the experimental results for both the high dose and
low-dose group which allowed tracer distribution to be quantified directly from the
MPI signal intensity.