Radioactive liposomes

Abstract

Many methods of labeling liposomes with both diagnostic and therapeutic radionuclides have been developed since the initial discovery of liposomes 40 years ago. Diagnostic radiolabels can be used to track nanometer-sized liposomes in the body in a quantitative fashion. This article reviews the basic methods of single photon emission computed tomography (SPECT) and positron emission tomography (PET) imaging and labeling of liposomes with single photon and dual photon positron emission radionuclides. Examples of the use of these diagnostic imaging agents will be shown. The ability to track the uptake of liposomes in humans and research animals on a whole body basis is providing researchers with an excellent tool for developing liposome-based drug delivery agents. The attachment of therapeutic radionuclides to liposomes also has great promise in cancer therapy. Recent developments in the use of liposomes carrying therapeutic radionuclides for cancer therapy will also be reviewed. Many of the radiolabeling and tracking technologies developed for nanosized liposomes will also be useful for the imaging and tracking of other nanoparticles.

Liposomes with conjugates of a calix[4]arene and a Gd-DOTA derivative on the outside surface; an efficient potential contrast agent for MRI

“…The best-fit parameters (see Fig. 2 (lines) and ESIw) are in the range to be expected based on values obtained for the previously studied low-molecular weight calix [4]arene system. 10 Attempts to prepare liposomes with about equal amounts of chelate on the inner and outer membrane layer with the use of the ''classical'' preparation protocol 6,12 failed; cryo-TEM images showed that complex mixtures of aggregates with a high content of disk-like micelles (bicelles) along with vesicles that were not completely closed or multilamellar (see ESIw) were always obtained.…”

“…PET and SPECT) in their cavities. 4 A disadvantage of liposome systems with MRI CAs incorporated in the membrane is that in the systems reported to date, half of the Gd-chelate molecules are oriented inside. These Gd-chelates have poor relaxivities caused by the low water permeability (P w ) of the hydrophobic membranes.…”

“…6 Higher r 1 can be reached by the design of systems with higher P w , but these may have decreased serum stability. Here, we report the preparation and characterization of a system with very high relaxivity by inclusion of calix [4]arene 1 ( Fig. 1) into the outer layer of the membrane of DSPC/DSPE-PEG2000-OMe/cholesterol liposomes.…”

“…Ipsonitration and subsequent reduction yielded a tetra-amino-calix [4]arene that was coupled with tert-butyl-DO3A-monoacid. After deprotection of the tertbutyl functions, the ligand was complexed with Gd(III).…”

“…These were performed by means of a two-step model that considers the system as an aqueous solution of Gd-chelates in the interior of the liposome with the included water molecules being in exchange with the Gd-chelates and the bulk water outside of it. With the use of parameters estimated from those for the previously studied calix [4]arene systems 10 and assuming that 50% of the chelates are located inside the vesicles (f in = 0.5), a temperature jump in relaxivity of 5 s À1 mM À1 is expected if the residence time of water in the cavity of the liposomes decreases from 9.1 (the value corresponding to P m ) to 0.1 ms. By contrast, the relaxivity remains almost constant when f in is zero (see ESIw). From these simulations, it may be concluded that at least 80% of the Gd-chelates are oriented towards the outside of the liposomes.…”