Biomedical Engineering Reference
In-Depth Information
and spleen (minor), targeting Kupffer cells as well as parenchymal cells. a few years
later (1974), this contrast agent was applied to cancer patients [24] to monitor the
deposition of a liposome carrying radiopharmaceutical to the area of treatment. It
was, in fact, the first time liposomes were administered into humans.
realizing the potential of radiolabeled liposomes in imaging, groups of v. caride
from Yale and v. richardson from University of london in the middle of 1970s
developed a
99m
Tc-labeled liposome for tumor detection [25, 26]. By that time, the
medical community recognized
99m
Tc as an excellent radioisotope for diagnostics
because of its short half-life of approximately 6 h allowing for the complete clearance
of radioactivity after 24 h and, also, readily detectable 140 kev γ-rays by conven-
tional X-ray diagnostic equipment.
99m
Tc labels were attached to a variety of pre-
formed liposomes made from phosphatidylcholine and cholesterol via a so-called tin
chloride method shown in figure 1.7. This method allowed
99m
Tc originally gener-
ated in the form of highly hydrophilic pertechnetate anion TcO
4
−
, to be reduced into
more hydrophobic Tc
3+
compound and be integrated into organic environments.
Upon administration of this radiolabeled liposome to mice, a significant increase of
the clearance rate of radioactivity was achieved compared to free pertechnetate.
More importantly, the preferential uptake of the contrast agent by tumors was
observed. However, the liposomes with Tc
3+
had low stability
in vivo
resulting in the
dissociation of the radionuclide from the liposome. Hence, the tin chloride reduction
method was later enhanced by the addition of
99m
Tc-specific chelators.
around the same time in the 1970s, the group of J. Baldeschwieler from Stanford
University came up with the visualization of liposomes from another angle. The
original intention of the group was to develop a technique for monitoring the release
of a therapeutic cargo from the liposomes. certain isotopes, such as
111
In known well
today, sequentially emit two gamma-rays of different energy. These two sequential
emissions can be measured by a technique known as gamma-ray perturbed angular
correlation (Pac) coincidence spectroscopy. The result of the measurement is a
parameter that is related to the rotational correlation time of the label. Molecules
trapped inside the liposomes rotate faster than the released ones and bound by high-
molecular-weight serum proteins. Hence, the change of the environment affects
(perturbs) the angular correlation and alters its rotational time. In the series of pub-
lications from 1972 to 1980, the group refined this technique, synthesized a variety
of
111
In carrying liposomes, measured the liposomes' structural integrity
in vivo
, and
99m
TcO
4
SnCl
2
SnCl
4
99m
Tc
3+
99m
TcO
4
99m
Tc
3+
99m
TcO
4
figure 1.7
formation of
99m
Tc liposomes via tin chloride method. (Based on ref. [25].)
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