Monitoring the Effect of Doxorubicin Liposomal in VX2 Tumor Using Magnetic Resonance Imaging
Cancer is still one of the serious diseases threatening
the lives of human beings. How to have an early diagnosis and
effective treatment for tumors is a very important issue. The animal
carcinoma model can provide a simulation tool for the studies of
pathogenesis, biological characteristics, and therapeutic effects.
Recently, drug delivery systems have been rapidly developed to
effectively improve the therapeutic effects. Liposome plays an
increasingly important role in clinical diagnosis and therapy for
delivering a pharmaceutic or contrast agent to the targeted sites.
Liposome can be absorbed and excreted by the human body, and is
well known that no harm to the human body. This study aimed to
compare the therapeutic effects between encapsulated (doxorubicin
liposomal, Lipodox) and un-encapsulated (doxorubicin, Dox)
anti-tumor drugs using magnetic resonance imaging (MRI).
Twenty-four New Zealand rabbits implanted with VX2 carcinoma at
left thighs were classified into three groups: control group (untreated),
Dox-treated group, and LipoDox-treated group, 8 rabbits for each
group. MRI scans were performed three days after tumor implantation.
A 1.5T GE Signa HDxt whole body MRI scanner with a high
resolution knee coil was used in this study. After a 3-plane localizer
scan was performed, three-dimensional (3D) fast spin echo (FSE)
T2-weighted Images (T2WI) was used for tumor volumetric
quantification. Afterwards, two-dimensional (2D) spoiled gradient
recalled echo (SPGR) dynamic contrast-enhanced (DCE) MRI was
used for tumor perfusion evaluation. DCE-MRI was designed to
acquire four baseline images, followed by contrast agent Gd-DOTA
injection through the ear vein of rabbit. A series of 32 images were
acquired to observe the signals change over time in the tumor and
muscle. The MRI scanning was scheduled on a weekly basis for a
period of four weeks to observe the tumor progression longitudinally.
The Dox and LipoDox treatments were prescribed 3 times in the first
week immediately after the first MRI scan; i.e. 3 days after VX2 tumor
implantation. ImageJ was used to quantitate tumor volume and time
course signal enhancement on DCE images. The changes of tumor size
showed that the growth of VX2 tumors was effectively inhibited for
both LipoDox-treated and Dox-treated groups. Furthermore, the tumor
volume of LipoDox-treated group was significantly lower than that of
Dox-treated group, which implies that LipoDox has better therapeutic effect than Dox. The signal intensity of LipoDox-treated group is
significantly lower than that of the other two groups, which implies
that targeted therapeutic drug remained in the tumor tissue. This study
provides a radiation-free and non-invasive MRI method for
therapeutic monitoring of targeted liposome on an animal tumor
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