In internal radiation therapy of unresectable liver tumors, microspheres containing a radionuclide are injected in the hepatic artery to achieve a preferential deposition of microspheres in the lesions. In this study, MR imaging techniques for qualitative and quantitative assessment of the biodistribution of holmiumloaded microspheres (HoMS) were investigated for their use in selective internal radiation therapy of liver tumors. To achieve this goal, the relaxivity of HoMS was first investigated in gel experiments. The resultant calibration curve was subsequently employed to quantify the biodistribution of HoMS administered to 13 excised rabbit livers and to the livers of 3 live rabbits with an implanted tumor. Finally, the feasibility of MR imaging of the biodistribution during treatment of a large animal was investigated by MR imaging of hepatic administration of HoMS to a live pig. Overall, the study showed that MRI can clearly depict the biodistribution of HoMS, but that quantification by means of the gel calibration curve yields an underestimation that increases for higher amounts of HoMS For the treatment of unresectable liver cancer selective internal radiation therapy has been proposed (1). In this therapy, radioactive microspheres are injected intra-arterially. Because tumor growth demands highly oxygenated blood, tumors and metastases often develop new vessels, branching off the hepatic artery. Injection of properly sized microspheres in the hepatic artery will result in a preferential deposition of the spheres in the lesions, based on the difference in demand of hepatic blood flow between tumors and normal liver tissue (2).Recently, holmium-loaded poly (L-lactic acid) microspheres (HoMS) have been developed (3). Before administration of the microspheres, a small fraction of 165 Ho (about 7 ppm) is activated by irradiation with neutrons in a high flux reactor. This activation produces the 166 Ho radionuclide (with a half-life T 1/2 of 26.8 hr), resulting in emission of ␤ particles (E max ϭ 1.84 MeV) and also photons (81 keV). The latter allow imaging of the distribution of the activated microspheres with scintigraphic cameras (4). Unfortunately, scintigraphic cameras only image microspheres and so give no information on the surrounding anatomy, e.g., the targeted tumor. However, due to the paramagnetic nature of holmium (being a lanthanide like gadolinium), both activated and nonactivated microspheres can be detected with MRI techniques.Compared to conventional nuclear imaging, the use of MRI in internal radiation therapy is expected to have some distinct advantages: First, because of the adjustable softtissue contrast, higher resolution, and dynamic imaging capabilities of MRI, detection of tumors and metastases and guidance and follow-up of therapy is facilitated. Second, unlike nuclear imaging, MRI does not rely on activation, but measures the biodistribution of activated and nonactivated HoMS with equal sensitivity. This means that a nonradioactive tracer dose (typically a few percent of a therapeu...

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Many advanced molecular imaging agents are currently being investigated preclinically. Especially, liposomes, have proven to be very promising carrier systems for diagnostic agents for use in single-photon emission computed tomography (SPECT) or magnetic resonance imaging (MRI), as well as for ther

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.