Activity measurements and determination of nuclear decay data of 166Ho in the MRTDosimetry project.

Holmium-166 is a high-energy ß--emitter radionuclide (~ 1.8 MeV) with a short half-life (~26.8h) that offers great potential as an alternative to 90Y for the treatment of liver cancer based on radioembolization. The possibility of quantitative Single Photon Emission Computed Tomography (SPECT) imaging of the main γ-ray emission at 80.6 keV, in addition to strong paramagnetic properties suitable for Magnetic Resonance Imaging (MRI), complement this therapeutic potential. The present paper describes the measurements carried out in three European radionuclide metrology laboratories for primary standardization of 166Ho and new determinations of X- and γ-ray photon-emission intensities in the framework of the European EMPIR project MRTDosimetry. New half-life measurements were also performed.

A novel ratiometric fluorescent probe based on 1, 8-naphthalimide for the detection of Ho3+ and its bioimaging.

A ratiometric fluorescent probe for the detection of Ho3+ in DMSO-aqueous medium was designed and synthesized based on 1, 8-naphthalimide. The probe displayed response to Ho3+ with a fluorescence decrease at 512nm and enhancement at 480nm, accompanying with a distinct fluorescence change from bright yellow-green to cyan. Besides, the probe exhibited a lower detection limit (6×10-8M) and could be used in intracellular fluorescence imaging. To the best of the knowledge, it was the first ratiometric fluorescent probe for Ho3+ detection. This probe was expected to be a useful tool for further elucidating the roles of Ho3+ in materials, biology and environment.

Simultaneous R2*, R2, and R2' quantification by combining S0 estimation of the free induction decay with a single spin echo: A single acquisition method for R2 insensitive quantification of holmium-166-loaded microspheres.

PURPOSE: To present a new method, S0 estimation of the free induction decay combined with a single spin echo measurement (SOFIDSE), that enables simultaneous measurements of R2*, R2, and R2' in order to quantify the local concentration of holmium microspheres (Ho-MS) for radioembolization. THEORY AND METHODS: SOFIDSE estimates R2* and the signal magnitude at time point 0, S0, from a multigradient echo readout of the free induction decay and subsequently estimates R2 using S0 and a single spin echo, from which R2' is deducted. The method was evaluated by comparing SOFIDSE R2 values with values obtained from shifted spin echo (SSE) measurements on a phantom setup containing Ho-MS and from dual spin echo measurements on a healthy volunteer. RESULTS: On average, SOFIDSE showed a small overestimation of R2 values compared with SSE independent of the microsphere concentration. R2' values determined by subtraction of either SOFIDSE R2 or SSE R2 from R2* showed excellent agreement (correlation coefficient = 1; P = 9 · 10(-11)). The Ho-MS-induced R2' values obtained by SOFIDSE were insensitive to the R2 value of the tissue in which they resided. CONCLUSION: SOFIDSE enables quantification of Ho-MS, in media with spatially or temporally varying R2 values, in a single acquisition.

Holmium(III)-selective fluorimetric optode based on N,N-bis(salicylidene)-naphthylene-1,8-diamine as a neutral fluorogenic ionophore.

For the first time a highly sensitive and selective fluorimetric optode for determination of trace amounts of Ho(3+) ions was prepared. The sensing system was prepared by incorporating of N,N-bis(salicylidene)-naphthylene-1,8-diamine (L) as a neutral Ho(3+)-selective fluoroionophore, in a plasticized PVC membrane containing sodium tetraphenyl borate as a lipophilic anionic additive. The response of the sensor is based on the strong fluorescence quenching of L by Ho(3+) ions. At pH 5.4, the proposed sensor displays a calibration curve over a wide concentration range of 1.0×10(-10)-1.0×10(-3)M, with a relatively fast response time of less than 1 min. In addition to high stability, high reproducibility and a relatively long working lifetime, the sensor shows a good selectivity towards Ho(3+) ion with respect to common coexisting cations. The fluorescence optode was applied to determination of holmium ion contents of water samples.

MRI-based biodistribution assessment of holmium-166 poly(L-lactic acid) microspheres after radioembolisation.

OBJECTIVES: To demonstrate the feasibility of MRI-based assessment of the intrahepatic Ho-PLLA-MS biodistribution after radioembolisation in order to estimate the absorbed radiation dose. METHODS: Fifteen patients were treated with holmium-166 ((166)Ho) poly(L-lactic acid)-loaded microspheres (Ho-PLLA-MS, mean 484 mg; range 408-593 mg) in a phase I study. Multi-echo gradient-echo MR images were acquired from which R (2) maps were constructed. The amount of Ho-PLLA-MS in the liver was determined by using the relaxivity r (2) of the Ho-PLLA-MS and compared with the administered amount. Quantitative single photon emission computed tomography (SPECT) was used for comparison with MRI regarding the whole liver absorbed radiation dose. RESULTS: R (2) maps visualised the deposition of Ho-PLLA-MS with great detail. The mean total amount of Ho-PLLA-MS detected in the liver based on MRI was 431 mg (range 236-666 mg) or 89 ± 19 % of the delivered amount (correlation coefficient r = 0.7; P < 0.01). A good correlation was found between the whole liver mean absorbed radiation dose as assessed by MRI and SPECT (correlation coefficient r = 0.927; P < 0.001). CONCLUSION: MRI-based dosimetry for holmium-166 radioembolisation is feasible. Biodistribution is visualised with great detail and quantitative measurements are possible.

A Ho(III) potentiometric polymeric membrane sensor based on a new four dentate neutral ion carrier.

In this research, we report a new Ho(3+)-PVC membrane electrode based on N-(4,5-dimethyl-2-(picolinamido)phenyl)picolinamide (H(2)Me(2)bpb) as a suitable ion carrier. Poly vinylchloride (PVC)-based membrane composed of H(2)Me(2)bpb with oleic acid (OA) as anionic additives, and o-nitrophenyloctyl ether (NPOE) as plasticized solvent mediator. The sensor exhibits a Nernstian slope of 20.1 ± 0.2 mV decade(-1) over the concentration range of 1.0 × 10(-6) to 1.0 × 1(-2) mol L(-1), and a detection limit of 5.0 × 10(-7) mol L(-1) of Ho(3+) ions. The potentiometric response of the sensor is independent of the solution pH in the range of 3.5-9.4. It has a very short response time, in the whole concentration range (<10s), and can be used for at least eight weeks. The proposed electrode shows a good selectivity towards Ho(3+) ions over a wide variety of cations, including alkali, alkaline earth, transition and heavy metal ions. To assess its analytical applicability the proposed Ho(3+) sensor was successfully applied as an indicator electrode in the titration of Ho(3+) ion solutions in certified reference materials, alloy samples and for the determination of the fluoride ion in two mouthwash preparations.

A new measurement of the half-life of (166m)Ho.

The work presented here is a new and precise measurement of the half-life of (166m)Ho by determining the activity concentration, using an ionisation chamber calibrated for this nuclide, and measuring the number of (166m)Ho atoms using multi-collector inductively coupled plasma mass spectrometry (MC-ICP-MS). Since the isotope (166)Er interferes with the mass spectrometric measurement, Er has to be eliminated from the (166m)Ho radioactive solution. The elimination was achieved using ion-exchange chromatography with the cation exchange resin Dowex AG 50W-X8 and 2-Hydroxybutanoic acid as the mobile phase. After a first transit through the chromatographic column, the purified (166m)Ho eluate was spiked with natural Er to get a resulting Er isotopic composition close to that of natural Er at better than 99.5%, and then it underwent two further separations to eliminate the Er. The activity concentration of this Er-free radioactive (166m)Ho solution was measured in our reference ionisation chamber calibrated for this nuclide by means of the 4πß(PC)-γ and 4πß(PS)-4πγ coincidence techniques and integral counting with a well-type NaI(Tl) detector and Monte Carlo efficiencies. An aliquot of this standardized solution was sent to the Paul Scherrer Institute (PSI) for mass concentration determination using an isotope dilution MC-ICP-MS approach. The mass concentration of (166m)Ho in this solution was determined with 0.25% relative standard uncertainty. This value was corroborated by two other independent measurements. The new half-life of (166m)Ho, 1132.6(39) years (k=1), is compatible with the value determined in 1965, but is 5.6% shorter and about 43 times more precise.

Standardization of (166m)Ho and 243Am/239Np by live-timed anti-coincidence counting with extending dead time.

The National Laboratory for Metrology of Ionizing Radiation (LNMRI)/Brazil acquired (166m)Ho and (243)Am/(239)Np solutions from commercial suppliers in order to realize primary standardization and therefore reducing the associated uncertainties. The method used in the standardization was the live-timed 4πß(LS)-γ(ΝaI(Tl)) anticoincidence counting. The live-timed anticoincidence system is operated since 2006 in LNMRI and is composed of two MTR2 modules donated by Laboratoire National Henri Becquerel (LNE-LNHB)/France. The data acquisition system uses a homemade LabView program and an Excel file for calculus. These systems have been used for primary standardization at LNMRI for many radionuclides and recently took part in the (124)Sb and (177)Lu International Key Comparisons with good performance.

A novel tracer technique for the assessment of fine sediment dynamics in urban water management systems.

Urban storm water run off can reduce the quality of receiving waters due to high sediment load and associated sediment-bound contaminants. Consequently, urban water management systems, such as detention ponds, that both modify water quantity through storage and improve water quality through sediment retention are frequently-used best management practices. To manage such systems effectively and to improve their efficiency, there is a need to understand the dynamics (transport and settling) of sediment, and in particular the fine sediment fraction (<63 µm) and its associated contaminants within urban storm water management systems. This can be difficult to achieve, as modelling the transport behaviour of fine-grained and cohesive sediment is problematic and field-based measurements can be costly, time-consuming and unrepresentative. The aim of this study was to test the application of a novel cohesive sediment tracer and to determine fine sediment transport dynamics within a storm water detention pond. The cohesive sediment tracer used was a holmium labelled montmorillonite clay which flocculated and had similar size and settling velocity to the natural pond sediment it was intended to mimic. The tracer demonstrated that fine sediment was deposited across the entire pond, with the presence of reed beds and water depth being important factors for maximising sediment retention. The results of the sediment tracer experiment were in good agreement with those of a mathematical sediment transport model. Here, the deposited sediment tracer was sampled by collecting and analysing surface pond sediments for holmium. However, analysis and sampling of the three dimensional suspended tracer 'cloud' may provide more accurate information regarding internal pond sediment dynamics.

Preparation, characterization and photocatalytic activities of holmium-doped titanium dioxide nanoparticles.

Holmium-doped TiO2 nanoparticles with high photocatalytic activities were prepared by sol-gel method and characterized by X-ray diffraction, transmission electron microscopy, ultraviolet-visible diffuse reflectance spectroscopy, and surface area measurement by nitrogen adsorption in this study. Experimental results indicated holmium doping could increase the surface area of TiO2 nanoparticles, and inhibit the growth of crystalline size and the anatase-to-rutile phase transformation. The results of photodegrading methyl orange showed holmium doping improved the photocatalytic activity of TiO2, and the reasons could be attributed to the synergetic effects of large surface areas, small crystallite size, lattice distortion and more charge imbalance of holmium-doped TiO2. In our experiment, the optimal doped amount was 0.3mol.% for the maximum photocatalytic degradation ratio when holmium-doped TiO2 was calcined at 500 degrees C, and the optimal calcined temperature was 600 degrees C when the doped amount was 0.5mol.%.

An absorbed dose map of bone tissue treated with a radiopharmaceutical in vivo.

A beagle humerus treated with Ho-chelate radiopharmaceutical in vivo was examined by electron paramagnetic resonance (EPR) dosimetry. The bone was sectioned and the absorbed dose to each bone fragment was determined by additive re-irradiation of the bone tissue with calibrated doses of gamma radiation. The measured doses ranged from 4.3 Gy to 62 Gy. The highest doses were recorded in the predominately trabecular bone tissue and the lowest doses in the predominately cortical bone tissue. The mean absorbed dose for the entire bone was 17 Gy. The data from 50 bone fragments were combined to create an absorbed dose map of the interior bone surface.

Vibrational spectra of mono, di and trimethyl ammonium double sulphates of rare earths Pr, Nd, Ho and Eu.

Infrared and Raman spectra of four rare earth (Ho, Eu, Nd and Pr) double sulphates have been recorded and analysed based on the vibrations of methyl ammonium cations, sulphate anions and water molecules. Formation of hydrogen bonds of the type N-H...O and O-H...O are identified in all the compounds. Bifurcated hydrogen bonds are present in the compounds with dimethyl ammonium cations. The sulphate anions are distorted and occupy a lower site symmetry in the compounds. The bands obtained for (CH(3))(2)NH(2) and SO(4)(2-) ions indicate that the structural bonding of (CH(3))(2)NH(2)Eu(SO(4))(2).H(2)O and (CH(3))(2)NH(2)Ho(SO(4))(2).4H(2)O is identical. Electronic transition bands of Eu(3+) and Nd(3+) observed in the Raman spectra of these two compounds have been identified and discussed.

Simultaneous spectrophotometric calibration of wavelength and absorbance in an interlaboratory survey using holmium oxide (Ho2O3) in perchloric acid as reference, compared with p-nitrophenol and cobaltous sulphate solutions (1978-1984).

The wavelength accuracy of ten different types of spectrophotometer was tested with holmium perchlorate solutions. It was found to be good, with mean deviations from the literature values of maximally 0.3 nm. Standard deviations over the entire spectral range were within 0.75 nm. The absorbance accuracy for different types of instruments was generally within 5%, except in the 287 nm range where higher deviations were found. The sharpness of the holmium peaks, in combination with band width and sensitivity of the instruments, troubled the majority of the participants. 150 spectrophotometers were involved in the surveys. Linearity of the spectrophotometers was tested with p-nitrophenol and cobaltous sulphate and found to be satisfactory.