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Local field inhomogeneities, that extend over areas largerthan one voxel size, change the applied imaging gradient and result in an echoshift in the readout direction and phase encoding direction. In this article,the field inhomogeneities that are caused by the presence of(super)paramagnetic (SPIO) particles in the human body are discussed. Thepresence of these particles eventually causes signal loss. Positive contrastmethods are an attempt to invert the dark contrast of the field perturbingstructures. Two categories of positive contrast techniques are presented:preprocessing and postprocessing methods. Among the acquisition methods thewhite marker techniques and the inversion recovery with on-resonance watersuppression (IRON) techniques will be treated. White marker conserves signalfrom regions with field inhomogeneities while the background is cancelled. IRONmethod suppresses the water protons which frequency is in the range of thesaturation radio frequency (RF) pulse. On the other hand, susceptibilitygradient mapping (SGM) is a postprocessing technique in which the positions ofthe echo shifts in k-space are calculated to determine the susceptibilityinduced gradient. For comparison the white marker and IRON technique can besimulated by postprocessing. The choice for a positive contrast techniquedepends on the application. It is a trade-off between the advantages and disadvantagesof each technique. However, postprocessing techniques are more promising forfuture research

Local field inhomogeneities, that extend over areas largerthan one voxel size, change the applied imaging gradient and result in an echoshift in the readout direction and phase encoding direction. In this article,the field inhomogeneities that are caused by the presence of(super)paramagnetic (SPIO) particles in the human body are discussed. Thepresence of these particles eventually causes signal loss. Positive contrastmethods are an attempt to invert the dark contrast of the field perturbingstructures. Two categories of positive contrast techniques are presented:preprocessing and postprocessing methods. Among the acquisition methods thewhite marker techniques and the inversion recovery with on-resonance watersuppression (IRON) techniques will be treated. White marker conserves signalfrom regions with field inhomogeneities while the background is cancelled. IRONmethod suppresses the water protons which frequency is in the range of thesaturation radio frequency (RF) pulse. On the other hand, susceptibilitygradient mapping (SGM) is a postprocessing technique in which the positions ofthe echo shifts in k-space are calculated to determine the susceptibilityinduced gradient. For comparison the white marker and IRON technique can besimulated by postprocessing. The choice for a positive contrast techniquedepends on the application. It is a trade-off between the advantages and disadvantagesof each technique. However, postprocessing techniques are more promising forfuture research

Local field inhomogeneities, that extend over areas largerthan one voxel size, change the applied imaging gradient and result in an echoshift in the readout direction and phase encoding direction. In this article,the field inhomogeneities that are caused by the presence of(super)paramagnetic (SPIO) particles in the human body are discussed. Thepresence of these particles eventually causes signal loss. Positive contrastmethods are an attempt to invert the dark contrast of the field perturbingstructures. Two categories of positive contrast techniques are presented:preprocessing and postprocessing methods. Among the acquisition methods thewhite marker techniques and the inversion recovery with on-resonance watersuppression (IRON) techniques will be treated. White marker conserves signalfrom regions with field inhomogeneities while the background is cancelled. IRONmethod suppresses the water protons which frequency is in the range of thesaturation radio frequency (RF) pulse. On the other hand, susceptibilitygradient mapping (SGM) is a postprocessing technique in which the positions ofthe echo shifts in k-space are calculated to determine the susceptibilityinduced gradient. For comparison the white marker and IRON technique can besimulated by postprocessing. The choice for a positive contrast techniquedepends on the application. It is a trade-off between the advantages and disadvantagesof each technique. However, postprocessing techniques are more promising forfuture research

Purpose The clinical application of holmium acetylacetonate microspheres (HoAcAcMS) for the intratumoral radionuclide treatment of solid malignancies requires a thorough understanding of their stability. Therefore, an in vitro and an in vivo stability study with HoAcAcMS was conducted. Methods HoAcAcMS, before and after neutron irradiation, were incubated in a phosphate buffer at 37°C for 6 months. The in vitro release of holmium in this buffer after 6 months was 0.5%. Elemental analysis, scanning electron microscopy, infrared spectroscopy and time of flight secondary ion mass spectrometry were performed on the HoAcAcMS. Results After 4 days in buffer the acetylacetonate ligands were replaced by phosphate, without altering the particle size and surface morphology. HoAcAcMS before and after neutron irradiation were administered intratumorally in VX2 tumor-bearing rabbits. No holmium was detected in the faeces, urine, femur and blood. Histological examination of the tumor revealed clusters of intact microspheres amidst necrotic tissue after 30 days. Conclusion HoAcAcMS are stable both in vitro and in vivo and are suitable for intratumoral radionuclide treatment., Radiation, Radionuclides and Reactors, Applied Sciences

Purpose The clinical application of holmium acetylacetonate microspheres (HoAcAcMS) for the intratumoral radionuclide treatment of solid malignancies requires a thorough understanding of their stability. Therefore, an in vitro and an in vivo stability study with HoAcAcMS was conducted. Methods HoAcAcMS, before and after neutron irradiation, were incubated in a phosphate buffer at 37°C for 6 months. The in vitro release of holmium in this buffer after 6 months was 0.5%. Elemental analysis, scanning electron microscopy, infrared spectroscopy and time of flight secondary ion mass spectrometry were performed on the HoAcAcMS. Results After 4 days in buffer the acetylacetonate ligands were replaced by phosphate, without altering the particle size and surface morphology. HoAcAcMS before and after neutron irradiation were administered intratumorally in VX2 tumor-bearing rabbits. No holmium was detected in the faeces, urine, femur and blood. Histological examination of the tumor revealed clusters of intact microspheres amidst necrotic tissue after 30 days. Conclusion HoAcAcMS are stable both in vitro and in vivo and are suitable for intratumoral radionuclide treatment., Radiation, Radionuclides and Reactors, Applied Sciences

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. 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). 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. 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.

Radiation, Radionuclides and Reactors, Applied Sciences

Radiation, Radionuclides and Reactors, Applied Sciences

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 therapeutic agents to treat diseases such as cancer. In this study, nanosized liposomes were designed and labeled with the radionuclides, holmium-166 (both a beta- and gamma-emitter and also highly paramagnetic) or technetium-99m, and coloaded with paramagnetic gadolinium allowing multimodality SPECT and MR imaging and radionuclide therapy with one single agent. Methods: Diethylenetriaminepentaacetic acid bisoctadecylamide (an amphiphilic molecule with a chelating group suitable for labeling with radionuclides) and gadoliniumacetylacetonate (GdAcAc) (a small lipophilic paramagnetic molecule) were incorporated in liposomes. The liposomes were characterized by measuring their mean size and size distribution, gadolinium content, and radiochemical stability after incubation in human serum at 37°C. The MRI properties (in vitro) were determined by use of relaxivity measurements at 1.5 and 3.0 Tesla in order to evaluate their potency as imaging agents. Results: The liposomes were successfully labeled with holmium-166, resulting in a high labeling efficiency (95% ± 1%) and radiochemical stability (> 98% after 48 hours of incubation), and coloaded with GdAcAc. Labeling of liposomes with technetium-99m was somewhat less efficient (85% ± 2%), although their radiochemical stability was sufficient (95% ± 1% after 6 hours of incubation). MRI measurements showed that the incorporation of GdAcAc had a strong effect on the MRI relaxivity. Conclusions: The synthesized liposomes allow for multimodality imaging and therapy, which makes these new agents highly attractive for future applications, Radiation, Radionuclides and Reactors, Applied Sciences

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 therapeutic agents to treat diseases such as cancer. In this study, nanosized liposomes were designed and labeled with the radionuclides, holmium-166 (both a beta- and gamma-emitter and also highly paramagnetic) or technetium-99m, and coloaded with paramagnetic gadolinium allowing multimodality SPECT and MR imaging and radionuclide therapy with one single agent. Methods: Diethylenetriaminepentaacetic acid bisoctadecylamide (an amphiphilic molecule with a chelating group suitable for labeling with radionuclides) and gadoliniumacetylacetonate (GdAcAc) (a small lipophilic paramagnetic molecule) were incorporated in liposomes. The liposomes were characterized by measuring their mean size and size distribution, gadolinium content, and radiochemical stability after incubation in human serum at 37°C. The MRI properties (in vitro) were determined by use of relaxivity measurements at 1.5 and 3.0 Tesla in order to evaluate their potency as imaging agents. Results: The liposomes were successfully labeled with holmium-166, resulting in a high labeling efficiency (95% ± 1%) and radiochemical stability (> 98% after 48 hours of incubation), and coloaded with GdAcAc. Labeling of liposomes with technetium-99m was somewhat less efficient (85% ± 2%), although their radiochemical stability was sufficient (95% ± 1% after 6 hours of incubation). MRI measurements showed that the incorporation of GdAcAc had a strong effect on the MRI relaxivity. Conclusions: The synthesized liposomes allow for multimodality imaging and therapy, which makes these new agents highly attractive for future applications, Radiation, Radionuclides and Reactors, Applied Sciences

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., Radiation, Radionuclides and Reactors, Applied Sciences

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., Radiation, Radionuclides and Reactors, Applied Sciences