diethylethylenediamine (BMEDA) chelator for the treatment of human non–small
cell lung cancer cells (NCI-H292) in a xenograft tumor model [25]. The pharmacokinetics and the dosimetry of
188 Re-BMEDA and
188 Re-PEG-liposome were
revealed by SPECT/CT imaging and the concurrent biodistribution analysis.
Compared with
188 Re-BMEDA,
188 Re-PEG-liposome showed a longer mean residence time, larger maximal concentration, and a slower pace of clearance. The
accumulation of
188 Re-PEG-liposome at the tumor site remained detectable up to
48 h. The maximal absorbed dose to the liver, spleen and subcutaneous tumor
(300 mm3) was estimated at 4 Sv, 17 Sv, and 70 Gy, respectively. When the tumor
growth was monitored up to 21 d, only
188 Re-PEG-liposome suppressed tumor
growth and extended life span of tumor bearing mice.
The high killing efficacy of alpha particles arises from the high linear energy
transfer (LET). LET is the amount of energy deposited per unit distance traveled.
Due to high LET, alpha particles therapy is independent of the cellular oxygenation
or cell cycle. The range of alpha particles in the tissues is short as 50–100 lm. So
their irradiation are well localized to the target cells, while surrounding healthy
tissues are minimally exposed. Immuno-liposomes labeled with alpha emitters,
213 Bi (t½ = 46 min) were injected in mice with breast cancer metastases induced by
intra-cardiac injection of rat HER-2/neu expressing syngeneic tumor cells [26].
213 Bi and the rat HER2/neu antibody was conjugated to a 100 nm diameter liposome. Median survival times were similar to those obtained with antibody conjugated with
213 Bi.
5.3 Albumin
Albumin is the most abundant plasma protein which is synthesized in the liver and
constitutes approximately 60% of total plasma protein. Its distribution is primarily
intravascular and its plasma half-life is 19 days [27]. Its molecular weight is
66.5 kDa and small enough to filter out through glomerulus in the kidney. Like
antibodies, albumin binds to the neonatal Fc receptor (FcRn) which is expressed in
proximal tubular cells, and is reabsorbed [28]. Albumin is a carrier protein for
steroids, thyroid hormone, retinoid, other lipophilic hormones, and lipophilic drugs
(Fig. 5.2).
When Evans blue-albumin complex was injected into tumor bearing mice via a
tail vein, it gradually accumulated in the tumor [29]. When Evans blue-albumin
complex was injected into the solid tumor, it was retained in the tumor for a long
period. This phenomenon is now called the EPR effect on the tumor. Many
nano-drug delivery systems, including liposome, use this strategy for the passive
targeting of tumors. Abraxane
® is a NP albumin-bound paclitaxel (PTX) and
became the first albumin based antineoplastic agent approved by the FDA.
Radiolabeled human serum albumin (HSA) was used for the detection of protein
losing enteropathy [30].
99m Tc-HSA scan showed blood pool imaging reflecting its
intravascular distribution. In patients with protein losing enteropathy, radioactivity
5 Organic Nanomaterials: Liposomes, Albumin, Dendrimer …
111
cell lung cancer cells (NCI-H292) in a xenograft tumor model [25]. The pharmacokinetics and the dosimetry of
188 Re-BMEDA and
188 Re-PEG-liposome were
revealed by SPECT/CT imaging and the concurrent biodistribution analysis.
Compared with
188 Re-BMEDA,
188 Re-PEG-liposome showed a longer mean residence time, larger maximal concentration, and a slower pace of clearance. The
accumulation of
188 Re-PEG-liposome at the tumor site remained detectable up to
48 h. The maximal absorbed dose to the liver, spleen and subcutaneous tumor
(300 mm3) was estimated at 4 Sv, 17 Sv, and 70 Gy, respectively. When the tumor
growth was monitored up to 21 d, only
188 Re-PEG-liposome suppressed tumor
growth and extended life span of tumor bearing mice.
The high killing efficacy of alpha particles arises from the high linear energy
transfer (LET). LET is the amount of energy deposited per unit distance traveled.
Due to high LET, alpha particles therapy is independent of the cellular oxygenation
or cell cycle. The range of alpha particles in the tissues is short as 50–100 lm. So
their irradiation are well localized to the target cells, while surrounding healthy
tissues are minimally exposed. Immuno-liposomes labeled with alpha emitters,
213 Bi (t½ = 46 min) were injected in mice with breast cancer metastases induced by
intra-cardiac injection of rat HER-2/neu expressing syngeneic tumor cells [26].
213 Bi and the rat HER2/neu antibody was conjugated to a 100 nm diameter liposome. Median survival times were similar to those obtained with antibody conjugated with
213 Bi.
5.3 Albumin
Albumin is the most abundant plasma protein which is synthesized in the liver and
constitutes approximately 60% of total plasma protein. Its distribution is primarily
intravascular and its plasma half-life is 19 days [27]. Its molecular weight is
66.5 kDa and small enough to filter out through glomerulus in the kidney. Like
antibodies, albumin binds to the neonatal Fc receptor (FcRn) which is expressed in
proximal tubular cells, and is reabsorbed [28]. Albumin is a carrier protein for
steroids, thyroid hormone, retinoid, other lipophilic hormones, and lipophilic drugs
(Fig. 5.2).
When Evans blue-albumin complex was injected into tumor bearing mice via a
tail vein, it gradually accumulated in the tumor [29]. When Evans blue-albumin
complex was injected into the solid tumor, it was retained in the tumor for a long
period. This phenomenon is now called the EPR effect on the tumor. Many
nano-drug delivery systems, including liposome, use this strategy for the passive
targeting of tumors. Abraxane
® is a NP albumin-bound paclitaxel (PTX) and
became the first albumin based antineoplastic agent approved by the FDA.
Radiolabeled human serum albumin (HSA) was used for the detection of protein
losing enteropathy [30].
99m Tc-HSA scan showed blood pool imaging reflecting its
intravascular distribution. In patients with protein losing enteropathy, radioactivity
5 Organic Nanomaterials: Liposomes, Albumin, Dendrimer …
111