Microspheres with Ultrahigh Holmium Content for Radioablation of Malignancies

Abstract

Purpose. The aim of this study was to develop microspheres with an ultra high holmium content which can be neutron activated for radioablation of malignancies. These microspheres are proposed to be delivered selectively through either intratumoral injections into solid tumors or administered via an intravascularly placed catheter. Methods. Microspheres were prepared by solvent evaporation, using holmium acetylacetonate (HoAcAc) crystals as the sole ingredient. Microspheres were characterized using light and scanning electron microscopy, coulter counter, titrimetry, infrared and Raman spectroscopy, differential scanning calorimetry, X-ray powder diffraction, magnetic resonance imaging (MRI), and X-ray computed tomography (CT). Results. Microspheres, thus prepared displayed a smooth surface. The holmium content of the HoAcAc microspheres (44% (w/w)) was higher than the holmium content of the starting material, HoAcAc crystals (33% (w/w)). This was attributed to the loss of acetylacetonate from the HoAcAc complex, during rearrangement of acetylacetonate around the holmium ion. The increase of the holmium content allows for the detection of (sub)microgram amounts of microspheres using MRI and CT. Conclusions. HoAcAc microspheres with an ultra-high holmium content were prepared. These microspheres are suitable for radioablation of tumors by intratumoral injections or treatment of liver tumors through transcatheter administration.

Radioactive Holmium Acetylacetonate Microspheres for Interstitial Microbrachytherapy: An In Vitro and In Vivo Stability Study

“…The microspheres had a holmium load of 45 ± 1%, and a size of 15 μm (97% of the microspheres between 10 and 20 μm) after sieving. As previously observed, no differences in size distribution were observed before and after neutron irradiation, irrespective of irradiation time (12). …”

“…Microsphere characteristics of the HoAcAcMS used in these experiments were in accordance with previous work (12). The microspheres had a holmium load of 45 ± 1%, and a size of 15 μm (97% of the microspheres between 10 and 20 μm) after sieving.…”

“…HoAcAcMS with a size of 15 μm were prepared by a solvent evaporation process previously described (12). The HoAcAcMS (300 or 600 mg) were weighed in high density polyethylene vials (Type A, Posthumus plastics, Beverwijk, the Netherlands).…”

“…Chitosan as a delivery device for 166 Ho however is not ideal due to leakage of 166 Ho from the complex, causing haematologic side effects. To further optimize the intratumoral application of 166 Ho, holmium microspheres with an ultra high holmium load were proposed as a radioablation device for solid malignancies (12). These microspheres were suitable to deliver sufficient radiation after intratumoral administration, and their efficacy was tested in a renal cell carcinoma tumor-bearing mouse model (13).…”

Chemoradiotherapeutic wrinkled mesoporous silica nanoparticles for use in cancer therapy

“…Holmium acetylacetonate encapsulated in PLLA nanoparticles were irradiated in a neutron flux of 1.1 × 10 13 neutrons/cm 2 s for 1 h, yielding a specific activity of approximately 74.85 µCi/mg which was suitable for intratumoral administration by the targeted multitherapy (TMT) technique. 56 Bult et al reported holmium acetylacetonate nanoparticles for solid malignancies with a radioactivity of 324 µCi/mg after activation in a neutron flux of approximately 5 × 10 12 neutrons/cm 2 s for 1 h. 18 The radioactivities obtained here for the 166 Ho-MS nanoparticles are comparable to that of the previously reported nanoparticles; thus, a therapeutic level can be achieved.…”