Lanthanide Bearing Microparticulate Systems for Multi-Modality Imaging and Targeted Therapy of Cancer

Abstract

The rapid developments of high-resolution imaging techniques are offering unique possibilities for the guidance and follow up of recently developed sophisticated anticancer therapies. Advanced biodegradable drug delivery systems, e.g. based on liposomes and polymeric nanoparticles or microparticles, are very effective tools to carry these anticancer agents to their site of action. Elements from the group of lanthanides have very interesting physical characteristics for imaging applications and are the ideal candidates to be co-loaded either in their non-radioactive or radioactive form into these advanced drug delivery systems because of the following reasons: Firstly, they can be used both as magnetic resonance imaging (MRI) and computed tomography (CT) contrast agents and for single photon emission computed tomography (SPECT). Secondly, they can be used for radionuclide therapies which, importantly, can be monitored with SPECT, CT, and MRI. Thirdly, they have a relatively low toxicity, especially when they are complexed to ligands. This review gives a survey of the currently developed lanthanide-loaded microparticulate systems that are under investigation for cancer imaging and/or cancer therapy.

99mTc-Macroaggregated Albumin Poorly Predicts the Intrahepatic Distribution of 90Y Resin Microspheres in Hepatic Radioembolization

“…The radioisotope 166 Ho is embedded in microspheres of poly(L-lactic acid). It emits b-radiation (half-life, 26.8 h; maximum energy, 1.77 and 1.85 MeV) and g-radiation (g-energy, 80.6 keV) and is paramagnetic, because the element holmium is chemically part of the lanthanide group, like gadolinium (34)(35)(36). The microspheres can be visualized in vivo with several clinical imaging modalities, including SPECT and MR imaging (14,37,38).…”

Lanthanide-Loaded Liposomes for Multimodality Imaging and Therapy

“…All liposomes were coated with polyethylene glycol (by use of PEG-DSPE), as it has been reported that this polymer has a positive influence on the in vivo circulation time and the MRI characteristics of the liposomes. 4 Liposome batches were prepared in duplicate.…”

“…In order to compare the relaxation properties of GdAcAc-loaded liposomes with liposomes that were loaded with gadolinium by use of amphiphilic gadolinium derivates 4 (the conventional way to prepare paramagnetic liposomes), type A liposomes were also labeled with gadolinium by using the DTPA-lipid. Labeling of liposomes with gadolinium was done in the same way as described above for holmium-166, using the same molar amounts of gadoliniumchloride.…”

“…Furthermore, if multimodality imaging agents are also loaded with therapeutic agents, targeted therapy of, for example, cancer, can be subsequently visualized. 4 Specific imaging and targeted therapy can be achieved by using liposomes, which can be targeted to tumor sites by the coupling of socalled homing devices (e.g., [fragments] of antibodies, to the surface of liposomes). [5][6][7][8] These vesicles (ϳ50-500 nm) consist of an aqueous space surrounded by a lipid bilayer.…”

“…4 These liposomes were successful in the detection of lymph nodes 14 and the visualization of prostate adenocarcinoma in animal models. 15 Loading of liposomes with gadolinium can be achieved by incorporating amphiphilic gadolinium derivates into the liposomal bilayers 4 to obtain an enhanced MR contrast. This contrast generally results from the shortening of the longitudinal relaxation time (T 1 ) of the MRI signal by the local magnetic field inhomogeneities created by the loaded liposomes.…”