SPECT imaging, c-ray emitting radionuclides, such as
99m
Tc (t½ = 6 h) and
111 In
(t½ = 2.8 d) are used. For PET imaging,
64 Cu (t½ = 12.7 h) or
89 Zr (t½ = 3.3 d) is
preferred over
18 F (t½ = 110 min) or
68 Ga (t½ = 68 min). Some radionuclides such
as
166 Ho,
177 Lu,
131 I, and
188 Re emit both gamma and beta ray at the same time.
NPs labeled with these radionuclides can be used for simultaneous imaging and
therapy, so called radio-theranostics. Radionuclides emitting beta (
90 Y) or alpha ray
(
225 Ac or
213 Bi) can be used for targeted radionuclide therapy.
5.2 Liposomes
Liposomes are spherical vesicles organized as the phospholipid bilayer resembling
cell membranes. Ever since their discovery in 1965, liposomes have been extensively studied exploring their potential for diagnostic and therapeutic purposes [3].
The targeting property of liposomes is based on the enhanced permeability and
retention (EPR) effect, which is the increased vascular permeability found in tumors
or inflamed tissues [4]. Targeting efficacy and biodistribution are dependent on
factors such as size, composition, charge, and surface modification [5]. The size of
the liposomes is one of the key factor of affecting biodistribution. Liposomes are
primarily taken up by the liver when smaller than 70 nm, while taken up by the
spleen when larger than 200 nm [6]. Liposomes with a diameter of 100–200 nm
showed up-to fourfold higher uptake rate in the tumor compared to larger or smaller
vesicles due to increased circulation time [7]. Composition of the liposomes is
related with the in vivo stability. The addition of cholesterol to the phospholipids
results in increased rigidity and chemical stability of liposomes in physiological
conditions6. When conventional liposomes are administered intravenously, they
will be coated with plasma proteins and organized into the protein corona. The
protein corona covering liposomes acts as opsonins. Opsonins are circulating host
defense serum molecules which are attached to the surface of microbes or foreign
bodies, promoting their clearance by phagocytic pathways. Liposomes coated by
opsonins are recognized by the mononuclear phagocyte system and rapidly cleared
from the blood circulation [8]. Polyethylene glycol (PEG) can be coated on the
surface of liposomes to interfere opsonization. The first U.S. Food and Drug
Administration (FDA) approved liposomal formulation was PEGylated liposomal
doxorubicin (Doxil
® ). It was approved in 1995 [9].
Radiolabeled liposomes can be used to determine the biodistribution of liposomal drugs and provide theranostic opportunity in combination with therapeutic
and diagnostic agents [10]. Vescan
® , the first liposomal-based radiotracer formulation was developed as an imaging agent [11].
111 In-based ionophore was loaded
within the micellar structure of the liposomes. Although Vescan
® was not approved
by the FDA for commercial use, clinical trials provided a good understanding of the
patient’s liposome clearance rate and imaging in various tumors.
Various strategies have been developed for the radiolabeling of liposomes [12,
13]. The four major strategies are passive encapsulation [14], membrane labeling
5 Organic Nanomaterials: Liposomes, Albumin, Dendrimer …
107
99m
Tc (t½ = 6 h) and
111 In
(t½ = 2.8 d) are used. For PET imaging,
64 Cu (t½ = 12.7 h) or
89 Zr (t½ = 3.3 d) is
preferred over
18 F (t½ = 110 min) or
68 Ga (t½ = 68 min). Some radionuclides such
as
166 Ho,
177 Lu,
131 I, and
188 Re emit both gamma and beta ray at the same time.
NPs labeled with these radionuclides can be used for simultaneous imaging and
therapy, so called radio-theranostics. Radionuclides emitting beta (
90 Y) or alpha ray
(
225 Ac or
213 Bi) can be used for targeted radionuclide therapy.
5.2 Liposomes
Liposomes are spherical vesicles organized as the phospholipid bilayer resembling
cell membranes. Ever since their discovery in 1965, liposomes have been extensively studied exploring their potential for diagnostic and therapeutic purposes [3].
The targeting property of liposomes is based on the enhanced permeability and
retention (EPR) effect, which is the increased vascular permeability found in tumors
or inflamed tissues [4]. Targeting efficacy and biodistribution are dependent on
factors such as size, composition, charge, and surface modification [5]. The size of
the liposomes is one of the key factor of affecting biodistribution. Liposomes are
primarily taken up by the liver when smaller than 70 nm, while taken up by the
spleen when larger than 200 nm [6]. Liposomes with a diameter of 100–200 nm
showed up-to fourfold higher uptake rate in the tumor compared to larger or smaller
vesicles due to increased circulation time [7]. Composition of the liposomes is
related with the in vivo stability. The addition of cholesterol to the phospholipids
results in increased rigidity and chemical stability of liposomes in physiological
conditions6. When conventional liposomes are administered intravenously, they
will be coated with plasma proteins and organized into the protein corona. The
protein corona covering liposomes acts as opsonins. Opsonins are circulating host
defense serum molecules which are attached to the surface of microbes or foreign
bodies, promoting their clearance by phagocytic pathways. Liposomes coated by
opsonins are recognized by the mononuclear phagocyte system and rapidly cleared
from the blood circulation [8]. Polyethylene glycol (PEG) can be coated on the
surface of liposomes to interfere opsonization. The first U.S. Food and Drug
Administration (FDA) approved liposomal formulation was PEGylated liposomal
doxorubicin (Doxil
® ). It was approved in 1995 [9].
Radiolabeled liposomes can be used to determine the biodistribution of liposomal drugs and provide theranostic opportunity in combination with therapeutic
and diagnostic agents [10]. Vescan
® , the first liposomal-based radiotracer formulation was developed as an imaging agent [11].
111 In-based ionophore was loaded
within the micellar structure of the liposomes. Although Vescan
® was not approved
by the FDA for commercial use, clinical trials provided a good understanding of the
patient’s liposome clearance rate and imaging in various tumors.
Various strategies have been developed for the radiolabeling of liposomes [12,
13]. The four major strategies are passive encapsulation [14], membrane labeling
5 Organic Nanomaterials: Liposomes, Albumin, Dendrimer …
107