showed that scintigraphic imaging of infection and inflammation using radiolabeled
liposomes is safe, sensitive and specific.
PET imaging with radiolabeled liposomes has only been carried out in animal
models.
18 F and
68 Ga have been used to radiolabel liposomes and to image different
types of cancers. However, the short half-life of these radionuclides (110 and
68 min, respectively) is not optimal. Radionuclides with longer half-lives, like
64 Cu
(t½ = 12.7 h) and
89 Zr (t½ = 78.4 h) are needed to image the accumulation of
liposomes in tumors at later time points. PEGylated liposomes labeled with
64 Cu
were used to evaluate PET imaging of cancer. Biodistribution studies were done
using two different molar level of PEG (5 and 10 mol%) on the surface of
PEGylated liposomes with remote loaded
64 Cu in a xenograft mouse model with
human neuroendocrine tumor cells (NCI-H727). A significantly higher liposomal
uptake (%ID/g) was observed in small tumors compared to large tumors at the 24 h
(P < 0.001) and 48 h (P < 0.001) time points.
89 Zr can track liposomes over a week after injection. To quantify in vivo
pharmacokinetics of liposomal NPs, liposome was labeled with
89 Zr efficiently
using a method based on a rapid ligand exchange reaction between the
membrane-permeable
89
Zr(8-hydroxyquinolinate)4 complex and the hydrophilic
liposomal cavity-encapsulated deferoxamine (DFO) [24]. These
89 Zr-labeled liposomal NPs showed remarkable stability in phosphate-buffered saline and serum
without leakage of radioactivity. Radiolabel retention of them in fresh rat serum at
37 °C for 24 and 48 h was 95 and 94%, respectively. In the PET images, the KB
tumor xenografts were visible at 6 h, and became clearer at 24 h, and then the
signals became weaker at 48 h due to washing out of radio-activity in the endocytosed liposomes degraded over time. The pharmacokinetic analysis from the PET
images indicated that the radioactivity, at last, was gradually and in parts washed
out from the kidney and liver, or remainders were deposited in the bone over time.
The catabolism of the liposome-encapsulated
89 Zr-DFO in the liver caused release
of
89 Zr into the circulation, leading to its accumulation in bone.
Radiolabeling of drug-loaded liposomes enables a theranostic strategy which
allows monitoring the liposomes and their contents during therapy using radionuclide imaging. The combination of chemotherapy and radionuclide therapy will also
be possible, if the liposomes are loaded with chemotherapeutic drugs and also
labeled with beta emitting radionuclides, such as
90 Y,
131 I,
166 Ho,
177 Lu, and
188 Re
or with alpha-emitters, such as
213 Bi or
225 Ac. Some radionuclides such as
131 I,
166 Ho,
177 Lu, and
188 Re, emits both beta particles and gamma photons at the same
time. Since beta ray can destroy nearby cells, and gamma ray can escape from the
body and be captured by gamma cameras, radiolabeling of liposomes with these
radionuclides will enable theranostic on their own.
188 Re is a theranostic radionuclide because it emits both gamma rays and high
energy of beta particles (2.12 meV). Since its atomic radius and gamma energy
(155 keV) is similar to
99m Tc, both radionuclides can be labeled with the same
chemical methods and are optimal for gamma camera imaging. Moreover,
188 Re
can be conveniently produced by
188 W/
188 Re generator systems.
188 Re has been
embedded in PEGylated liposomal particles via N,N-bis(2-mercaptoethyl)- N′,N′110
K. W. Kang and M. G. Song
liposomes is safe, sensitive and specific.
PET imaging with radiolabeled liposomes has only been carried out in animal
models.
18 F and
68 Ga have been used to radiolabel liposomes and to image different
types of cancers. However, the short half-life of these radionuclides (110 and
68 min, respectively) is not optimal. Radionuclides with longer half-lives, like
64 Cu
(t½ = 12.7 h) and
89 Zr (t½ = 78.4 h) are needed to image the accumulation of
liposomes in tumors at later time points. PEGylated liposomes labeled with
64 Cu
were used to evaluate PET imaging of cancer. Biodistribution studies were done
using two different molar level of PEG (5 and 10 mol%) on the surface of
PEGylated liposomes with remote loaded
64 Cu in a xenograft mouse model with
human neuroendocrine tumor cells (NCI-H727). A significantly higher liposomal
uptake (%ID/g) was observed in small tumors compared to large tumors at the 24 h
(P < 0.001) and 48 h (P < 0.001) time points.
89 Zr can track liposomes over a week after injection. To quantify in vivo
pharmacokinetics of liposomal NPs, liposome was labeled with
89 Zr efficiently
using a method based on a rapid ligand exchange reaction between the
membrane-permeable
89
Zr(8-hydroxyquinolinate)4 complex and the hydrophilic
liposomal cavity-encapsulated deferoxamine (DFO) [24]. These
89 Zr-labeled liposomal NPs showed remarkable stability in phosphate-buffered saline and serum
without leakage of radioactivity. Radiolabel retention of them in fresh rat serum at
37 °C for 24 and 48 h was 95 and 94%, respectively. In the PET images, the KB
tumor xenografts were visible at 6 h, and became clearer at 24 h, and then the
signals became weaker at 48 h due to washing out of radio-activity in the endocytosed liposomes degraded over time. The pharmacokinetic analysis from the PET
images indicated that the radioactivity, at last, was gradually and in parts washed
out from the kidney and liver, or remainders were deposited in the bone over time.
The catabolism of the liposome-encapsulated
89 Zr-DFO in the liver caused release
of
89 Zr into the circulation, leading to its accumulation in bone.
Radiolabeling of drug-loaded liposomes enables a theranostic strategy which
allows monitoring the liposomes and their contents during therapy using radionuclide imaging. The combination of chemotherapy and radionuclide therapy will also
be possible, if the liposomes are loaded with chemotherapeutic drugs and also
labeled with beta emitting radionuclides, such as
90 Y,
131 I,
166 Ho,
177 Lu, and
188 Re
or with alpha-emitters, such as
213 Bi or
225 Ac. Some radionuclides such as
131 I,
166 Ho,
177 Lu, and
188 Re, emits both beta particles and gamma photons at the same
time. Since beta ray can destroy nearby cells, and gamma ray can escape from the
body and be captured by gamma cameras, radiolabeling of liposomes with these
radionuclides will enable theranostic on their own.
188 Re is a theranostic radionuclide because it emits both gamma rays and high
energy of beta particles (2.12 meV). Since its atomic radius and gamma energy
(155 keV) is similar to
99m Tc, both radionuclides can be labeled with the same
chemical methods and are optimal for gamma camera imaging. Moreover,
188 Re
can be conveniently produced by
188 W/
188 Re generator systems.
188 Re has been
embedded in PEGylated liposomal particles via N,N-bis(2-mercaptoethyl)- N′,N′110
K. W. Kang and M. G. Song