Lipid-Based Pharmaceutical Nanocarriers for Imaging Applications - Nanotechnology for Biomedical Imaging and Diagnostics - page 50

tissue attenuation, they also require different levels of the corresponding diagnostic
label to be delivered in the target region.
A large variety of techniques have been developed to load liposomes and lipid-
polymer micelles with different reporter labels. With the exception of gas-loaded
vesicles intended for ultrasound imaging, the following criteria were established
to be the main characteristics of a successful lipid nanovesicle labeling method:
(i) sufficient shelf stability of the formulation to be labeled; (ii) high labeling
efficiency; (iii) convenient and efficient labeling at room temperature; (iv) use of
readily available isotopes and metals that have good physical imaging characteris-
tics, dosimetry, and half-life; (v) reasonable in vitro and in vivo stability of label
association with the carriers; and (vi) universal applicability to all types of liposomes
and micelles, regardless of size, surface charge, or lipid composition [20, 21].
A number of general approaches developed for the labeling of liposomes—suc-
cessfully applied for lipid-polymer micelles also—are summarized here in order of
complexity and development from the poorer to higher in vivo stability [21].

3.2.1 Label encapsulation during Nanocarrier preparation

Lipid-based nanocarriers can be labeled by the incorporation of the gamma-imaging
agent into the lipid phase [22] or encapsulation in the aqueous interior of the vesicle
during formulation [23, 24]. This method has many disadvantages including low
encapsulation efficiency, high radiation exposure, difficulty in maintaining nanocar-
rier sterility, and the necessity of making nanocarriers within a very short period of
the intended clinical use, due to the overall instability of the formulation [20]. This is
particularly true with radioisotopes with half-lives under 24 h, which includes 99m Tc
and 18 f. The only method reported to date for labeling nanocarriers with a pET radio-
nuclide is the encapsulation of 18 f-fluorodeoxyglucose ( 18 f-fdg) (110 min half-life)
within vesicles during liposome and micelle manufacture [25]. The development of
methods to label nanocarriers with pET radionuclides after their manufacture will be
very valuable. A better approach is the labeling of nanocarriers after their manufac-
ture and just prior to use [26].

3.2.2 surface Labeling after Nanocarrier preparation

Nanocarriers can be labeled by attaching the radioisotope to the surface of pre-
formed phospholipid vesicles. This method in fact offers an improvement over the
encapsulation method as the preformed nanocarriers can be made in a different loca-
tion than the labeling site, where the labeling process can occur just prior to the
clinical use. This surface labeling employs the basic electrostatic interactions bet-
ween the charged isotope and the nanocarrier surface. Labeling using this method
has the problems of inconsistent labeling efficiencies and insufficient in vivo sta-
bility due to exposure of the external surface of nanocarriers to plasma proteins in
the circulation [20].
initial methods described for labeling postmanufactured liposomes with 99m Tc
relied on the labeling of the lipid membrane with reduced 99m Tc. This method proved