The surface chelation and stepped remote loading approaches are featuring high
radiolabeling efficiency and retention. Surface chelation uses chelators that are
incorporated into the hydrophobic membrane surface of the liposomes during their
formation. This method has high-efficiency loading of the liposomes (>90%). In
vivo stability of radionuclides labeled on the surface of liposomes is dependent on
the radionuclide–chelator binding constant. When the radionuclides are exposed to
biomolecules in the blood, it might be released from the chelator if the biding is not
tight enough. The remote loading method is active loading and concentrating of
radionuclides into the internal aqueous compartment of the liposomes. It provides
both high loading efficiencies (>90%) and high in vivo stability because the
radionuclides are located inside of liposome.
During the development of liposomal drugs,
99m
Tc and
111 In were popularly
used to monitor the fate of liposomes in vivo using tissue biodistribution studies
and scintigraphic imaging in earlier days, since their physical half-life is similar to
the biologic half time of liposomes [18–20]. Clinical studies provided insights in
the in vivo behavior of liposomes in cancer patients and guided the development of
liposomal drugs. Planar scan and SPECT imaging of PEG-coated and
111 In-labeled
liposomes succeeded in visualizing tumor lesions in different types of locally
advanced cancer [21]. Clinical studies with this companion diagnostic imaging
showed that liposomes were well tolerated in all patients and accumulated in the
tumor in 15 of 17 patients (4 of 5 breast, 5 of 5 head and neck, 3 of 4 bronchus, 2 of
2 glioma, and 1 of 1 cervix cancer). The tumor uptake of liposomes were 0.5–3.5%
of the injected dose at 72 h which was estimated from regions of interest on gamma
camera images. The highest uptake were observed in the patients with head and
neck cancers [33.0 ± 15.8%ID/kg (percentage of injected dose/kg)]. Radiolabeled
PEGylated liposomes accumulate in solid tumors and remain there according to the
imaging findings at 7 days after injection. In addition, significant localization of the
liposomes was found in the tissues of the mononuclear phagocytic system (MPS a.
k.a. RES; reticuloendothelial system) such as liver, spleen, and bone marrow. Due
to the low sensitivity (*70%) for detecting tumors, no radiolabeled liposomes were
approved for diagnostic agents by the FDA.
Since liposomes localize in inflamed tissues, gamma camera imaging with
radiolabeled liposomes was also applied to image infectious or inflammatory
lesions. PEGylated liposomal formulation was used to detect inflammatory foci in
patients.
99m
Tc-PEG liposome scintigraphy were directly compared with those of
111 In-immunoglobulin G (lgG) scintigraphy in patients with soft-tissue infection
(n = 3), septic arthritis (n = 3), autoimmune polyarthritis (n = 2), infected hip
prosthesis (n = 1), infected osteosynthesis (n = 1), spondylodiscitis (n = 1),
infected aortic prosthesis (n = 1), colitis (n = 1), abdominal abscess (n = 1), and
pneumonia (n = 1). Of the 16 proven lesions, 15 were detected by
99m Tc-PEG
liposome scan which is similar to
111 In-IgG imaging [22]. Radiolabeled liposomes
were also used to image inflamed foci in patients with rheumatoid arthritis.
99m Tc
labeled negatively charged liposomes were injected to 6 patients with rheumatoid
arthritis intravenously [23]. All clinically involved joints could be visualized on
scan 20–22 h later exception of the small interphalangeal joints. These studies
5 Organic Nanomaterials: Liposomes, Albumin, Dendrimer …
109
radiolabeling efficiency and retention. Surface chelation uses chelators that are
incorporated into the hydrophobic membrane surface of the liposomes during their
formation. This method has high-efficiency loading of the liposomes (>90%). In
vivo stability of radionuclides labeled on the surface of liposomes is dependent on
the radionuclide–chelator binding constant. When the radionuclides are exposed to
biomolecules in the blood, it might be released from the chelator if the biding is not
tight enough. The remote loading method is active loading and concentrating of
radionuclides into the internal aqueous compartment of the liposomes. It provides
both high loading efficiencies (>90%) and high in vivo stability because the
radionuclides are located inside of liposome.
During the development of liposomal drugs,
99m
Tc and
111 In were popularly
used to monitor the fate of liposomes in vivo using tissue biodistribution studies
and scintigraphic imaging in earlier days, since their physical half-life is similar to
the biologic half time of liposomes [18–20]. Clinical studies provided insights in
the in vivo behavior of liposomes in cancer patients and guided the development of
liposomal drugs. Planar scan and SPECT imaging of PEG-coated and
111 In-labeled
liposomes succeeded in visualizing tumor lesions in different types of locally
advanced cancer [21]. Clinical studies with this companion diagnostic imaging
showed that liposomes were well tolerated in all patients and accumulated in the
tumor in 15 of 17 patients (4 of 5 breast, 5 of 5 head and neck, 3 of 4 bronchus, 2 of
2 glioma, and 1 of 1 cervix cancer). The tumor uptake of liposomes were 0.5–3.5%
of the injected dose at 72 h which was estimated from regions of interest on gamma
camera images. The highest uptake were observed in the patients with head and
neck cancers [33.0 ± 15.8%ID/kg (percentage of injected dose/kg)]. Radiolabeled
PEGylated liposomes accumulate in solid tumors and remain there according to the
imaging findings at 7 days after injection. In addition, significant localization of the
liposomes was found in the tissues of the mononuclear phagocytic system (MPS a.
k.a. RES; reticuloendothelial system) such as liver, spleen, and bone marrow. Due
to the low sensitivity (*70%) for detecting tumors, no radiolabeled liposomes were
approved for diagnostic agents by the FDA.
Since liposomes localize in inflamed tissues, gamma camera imaging with
radiolabeled liposomes was also applied to image infectious or inflammatory
lesions. PEGylated liposomal formulation was used to detect inflammatory foci in
patients.
99m
Tc-PEG liposome scintigraphy were directly compared with those of
111 In-immunoglobulin G (lgG) scintigraphy in patients with soft-tissue infection
(n = 3), septic arthritis (n = 3), autoimmune polyarthritis (n = 2), infected hip
prosthesis (n = 1), infected osteosynthesis (n = 1), spondylodiscitis (n = 1),
infected aortic prosthesis (n = 1), colitis (n = 1), abdominal abscess (n = 1), and
pneumonia (n = 1). Of the 16 proven lesions, 15 were detected by
99m Tc-PEG
liposome scan which is similar to
111 In-IgG imaging [22]. Radiolabeled liposomes
were also used to image inflamed foci in patients with rheumatoid arthritis.
99m Tc
labeled negatively charged liposomes were injected to 6 patients with rheumatoid
arthritis intravenously [23]. All clinically involved joints could be visualized on
scan 20–22 h later exception of the small interphalangeal joints. These studies
5 Organic Nanomaterials: Liposomes, Albumin, Dendrimer …
109