Preparation and characterization of inorganic radioactive holmium-166 microspheres for internal radionuclide therapy.

Microspheres with high specific activities of radionuclides are very interesting for internal radiotherapy treatments. This work focuses on the formulation and characterization of inorganic microspheres with a high content of holmium and therefore a high specific radioactivity of holmium-166. Two novel formulations of inorganic microspheres were obtained by dispersing solid holmium acetylacetonate microspheres (Ho2(AcAc)3-ms) in NaH2PO4 or NaOH solutions followed by 2 h incubation at room temperature. By exchange of acetylacetonate with phosphate or hydroxyl ions, holmium phosphate microspheres (HoPO4-ms) and holmium hydroxide microspheres (Ho(OH)3-ms) were formed respectively. The inorganic microspheres had a significantly smaller diameter (28.5 ±â€¯4.4 µm (HoPO4-ms) and 25.1 ±â€¯3.5 µm (Ho(OH)3-ms)) than those of Ho2(AcAc)3-ms (32.6 ±â€¯5.2 µm). The weight percentage of holmium-165 in the microspheres increased significantly from 47% (Ho2(AcAc)3-ms) to 55% (HoPO4-ms) and 73% (Ho(OH)3-ms). After preparation of both HoPO4-ms and Ho(OH)3-ms, the stable holmium-165 isotope was partly converted by neutron activation into radioactive holmium-166 to yield radioactive microspheres. High specific activities were achieved ranging from 21.7 to 59.9 MBq/mg (166HoPO4-ms) and from 28.8 to 79.9 MBq/mg (166Ho(OH)3-ms) depending on the neutron activation time. The structure of both microspheres was preserved up to neutron activations of 6 h in a thermal neutron flux of 4.72 × 1016 n m-2 s-1. After activation, both microspheres revealed excellent stability in administration fluids (saline and phosphate buffer) having less than 0.05% of holmium released after 72 h incubation. Finally, the hemocompatibility of these inorganic microspheres was evaluated and it was shown that the microspheres did cause neither hemolysis nor depletion or inhibition of the coagulation factors of the intrinsic blood coagulation pathway meaning that the microspheres have a good hemocompatibility. Overall, this work shows that radioactive inorganic microspheres with high specific activities of holmium-166 can be prepared which potentially can be used for internal radionuclide therapy.

Application of Classical Thermodynamics to Conductivity in Nonpolar Media: Experimental Confirmation.

We previously proposed ( Gourdin-Bertin , S. and Chassagne , C. J. Chem. Phys. 2016 , 144 ( 24) ) a simple theoretical model to account for the evolution of conductivity with dielectric permittivity in nonpolar media. In this article, we validate the theory experimentally for the case of an ionogenic species kept at a constant chemical potential (i.e., in equilibrium with a nondissolved salt, in contrast to previously published conductivity measurements carried out as a function of various fully dissolved salt concentrations). To our knowledge, it is the first time that this type of experiment has been performed explicitly.

Application of classical thermodynamics to the conductivity in non-polar media.

Electrical conductivity in non-polar media is a subject which recently regained interest. If most of experiments and theoretical developments were done more than 50 years ago, new experiments and theories have been recently published. As the electrical conductivity describes, at low field, the equilibrium state of a system, it is natural to apply theories based on equilibrium thermodynamics. In this article, well-established classical thermodynamics and solvations models are applied to recently published data. This enables to get a new insight in intriguing phenomena, such as the linear dependence of the conductivity on the concentration of ionic surfactant and the evaluation of conductivity for the mixture of two miscible fluids, such as alcohol and alcane, which have very different conductivities.

Onsager's reciprocal relations in electrolyte solutions. I. Sedimentation and electroacoustics.

In the framework of irreversible thermodynamics, we show that the sedimentation current in electrolyte solutions is mathematically equivalent to the low frequency limit of the ionic vibration current, appearing in the presence of an acoustic wave. This non-trivial result is obtained thanks to a careful choice of the reference frame used to express the mass fluxes in the context of electroacoustics. Coupled transport phenomena in electrolyte solutions can also be investigated in a mechanical framework, with a set of Newtonian equations for the dynamics of charged solutes. Both in the context of sedimentation and of electroacoustics, we show that the results obtained in the mechanical framework, in the ideal case (i.e., without interactions between ions), do satisfy the Onsager's reciprocal relations. We also derive the general relation between corrective forces accounting for ionic interactions which must be fulfilled so that the Onsager's reciprocal relations are verified. Finally, we show that no additional diffusion term needs to be taken into account in the flux of solutes (far from the walls), even if local concentration gradients exist, contrarily to what was done previously in the literature.

Onsager's reciprocal relations in electrolyte solutions. II. Effect of ionic interactions on electroacoustics.

In electrolyte solutions, an electric potential difference, called the Ionic Vibration Potential (IVP), related to the ionic vibration intensity, is generated by the application of an acoustic wave. Several theories based on a mechanical framework have been proposed over the years to predict the IVP for high ionic strengths, in the case where interactions between ions have to be accounted for. In this paper, it is demonstrated that most of these theories are not consistent with Onsager's reciprocal relations. A new expression for the IVP will be presented that does fulfill the Onsager's reciprocal relations. We obtained this expression by deriving general expressions of the corrective forces describing non-ideal effects in electrolyte solutions.

Onsager's reciprocal relations for electroacoustic and sedimentation: Application to (concentrated) colloidal suspensions.

In this article, the relations for electroacoustic phenomena, such as sedimentation potential, sedimentation intensity, colloid vibration potential, colloid vibration intensity/current, or electric sonic amplitude, are given, on the basis of irreversible thermodynamics. This formalism allows in particular to discuss the different expressions for concentrated suspensions found by various authors, which are of great practical interest. It was found that some existing expressions have to be corrected. Relations between the electrophoretic mobilities assessed by the different experiments are derived.

Reciprocal relations in electroacoustics.

In a colloidal suspension, one can generate sound waves by the application of an alternating electric field (Electrokinetic Sonic Amplitude, i.e., ESA). Another phenomenon is electrophoresis (Electrophoretic Mobility, i.e., EM) where a colloidal particle moves relative to the solvent in an electric field. Vice versa one can generate electric fields or electric currents by sound waves (Colloid Vibration Potential/Current, i.e., CVP/CVI). In 1988 and 1990, O'Brien [J. Fluid Mech. 190, 71-86 (1988) and O'Brien, J. Fluid Mech. 212, 81-93 (1990)] derived a reciprocal relation between the proportionality coefficients of the EM and CVI phenomena. In this paper, we will generalize his proof by constructing the relevant entropy production from which the linear force-flux relations follow. General relations are derived for electrolyte solutions, of which colloidal suspensions are a particular case. The relations between CVI, CVP, EM, and ESA are discussed. O'Brien's reciprocal relation then follows as an Onsager relation. The relation is valid for any applied electric field frequency, particle surface charge and particle concentration (even in the presence of particle-particle interactions) provided the system is isotropic.

Comparison between the electrokinetic properties of kaolinite and montmorillonite suspensions at different volume fractions.

We have investigated the electrokinetic responses of two different kinds of clay particles, kaolinite and montmorillonite. The dielectric permittivity of kaolinite suspensions is linearly proportional to volume fraction up to volume fractions of 20%, whereas that of montmorillonite is deviating from a linear relationship, for volume fractions below 0.5%. This indicates that the montmorillonite particles experience a particle-particle interaction at these low volume fractions. The complex dipole coefficients of both clays estimated by experimental data are, however, within experimental error in good approximation independent on volume fraction and agree with the theoretical predictions. The relaxation frequency in clay-water system at low ionic strength is almost determined by the relaxation of the double layer for both kaolinite and montmorillonite. For volume fractions larger than 0.5% for montmorillonite, we find that the zeta potential measured by electroacoustic methods starts to depend strongly on volume fraction. It is expected that for these high volume fractions, the dipole coefficients will also become volume-fraction dependent.

Dielectric and electrophoretic response of montmorillonite particles as function of ionic strength.

Montmorillonite is a sheet-like clay mineral. The surface charge of the faces is always negative, whereas the surface charges of the edges depend on pH. In this study, pH is around 6.5 implying that the edges are slightly positive; however, the overall charge of the particle appears to be negative as the surface of the faces is 50 times larger than the edges. In the presence of an applied electric field, montmorillonite particles and their double layer will polarize. This polarization affects the electrokinetic response of the particles. In this article, we investigated the effect of ionic strength on the electrokinetic response of montmorillonite particles using the dielectric spectroscopy and electrophoretic mobility. The experimental dipole coefficient found by dielectric spectroscopy was compared to the semi-analytical formula presented by Chassagne [C. Chassagne, J. Colloid Interface Sci. 326 (2008)]. The amplitude of the dipole coefficient of montmorillonite particles increased and the relaxation frequency shifted to lower frequencies with decreasing ionic strength. This tendency is in qualitative agreement with the theoretical prediction. A better agreement between the experimental and theoretical amplitudes of the dipole coefficient and between the high-frequency experimental and theoretical mobilities was obtained when a Stern layer conductivity is introduced. The same values for the zeta potential and Stern layer conductivities were used in both measurement sets. The relaxation frequencies were not changed by addition of a Stern layer. This discrepancy between experimental and theoretical relaxation frequencies are due to the limitation of the theory that is not valid at low κa, as discussed in the conclusion.

Shear-induced flocculation of a suspension of kaolinite as function of pH and salt concentration.

The relation between the electrokinetic charge of kaolinite particles and their flocculation behavior has been investigated over a wide range of pH and added salt (for MgCl(2) and NaCl salts). All flocculation experiments have been done with a mixing jar (sediment volume concentration phi=3.84x10(-5)). The electrokinetic charge of particles in different suspensions has been assessed by electrophoresis while laser diffraction has been used to measure the floc size distribution. Mixing jar experiments can be successfully used to investigate the flocculation behavior of kaolinite at shear rates higher than or equal to G=35 s(-1), which is the shear rate used in the experiments. At lower shear rates, the floc size distribution is affected by particle settling. The electrophoretic mobility of kaolinite decreases in absolute value when the pH of the suspension decreases. This is reflected in an increase of both floc size and flocculation rate: the floc size at pH 4 is three times larger than at pH 7 and the flocculation time is one order of magnitude smaller (from 1000 to 100 min). When the ionic strength of the suspension is increased, the electrophoretic mobility and the mean floc size display the same variations. On addition of NaCl (pH 9) both the electrophoretic mobility and the floc size display an optimum around 1 mM of added salt, a feature that has been observed by other authors as well. The equilibrium floc size for a suspension (A) at 1 M of added NaCl and pH 9 is the same as for a suspension (B) at pH 2 with no added salt. However, the time needed to reach the equilibrium for suspension (A) is one order of magnitude larger than for suspension (B). This is due to edge-face Coulombic attraction in suspension (B). The equilibrium floc size obtained by addition of MgCl(2) or sea salt at pH 9 is similar to the size obtained by addition of NaCl. The flocculation rate for a suspension with added MgCl(2) is higher than for suspensions with other added salts.

Electrokinetic study of kaolinite suspensions.

In this article a new formula for the electrophoretic mobility of a spheroidal colloid is given. This formula and the formula presented in Chassagne and Bedeaux [C. Chassagne, D. Bedeaux, J. Colloid Interface Sci. 326 (2008) 240-253] for the dipolar coefficient of a spheroidal colloid are intertwined. The combination of electrophoresis and complex conductivity measurements (from which the dipolar coefficient can be derived) allows to assess both the zeta potential and the Stern layer conductance. We will in particular show that the values found for the zeta potential from both techniques are similar in the case of the kaolinite suspension studied. Electrophoretic mobility data are also presented and discussed for a wide range of ionic strengths, different types of salt and various pH. This data has been used in flocculation studies on the same kaolinite samples [F. Mietta, C. Chassagne, J.C. Winterwerp, J. Colloid Interface Sci., accepted for publication, doi:10.1016/j.jcis.2009.03.044].

The dielectric response of a colloidal spheroid.

In this article, we present a theory for the dielectric behavior of a colloidal spheroid, based on an improved version of a previously published analytical theory [C. Chassagne, D. Bedeaux, G.J.M. Koper, Physica A 317 (2003) 321-344]. The theory gives the dipolar coefficient of a dielectric spheroid in an electrolyte solution subjected to an oscillating electric field. In the special case of the sphere, this theory is shown to agree rather satisfactorily with the numerical solutions obtained by a code based on DeLacey and White's [E.H.B. DeLacey, L.R. White, J. Chem. Soc. Faraday Trans. 2 77 (1981) 2007] for all zeta potentials, frequencies and kappa a1 where kappa is the inverse of the Debye length and a is the radius of the sphere. Using the form of the analytical solution for a sphere we were able to derive a formula for the dipolar coefficient of a spheroid for all zeta potentials, frequencies and kappa a1. The expression we find is simpler and has a more general validity than the analytical expression proposed by O'Brien and Ward [R.W. O'Brien, D.N. Ward, J. Colloid Interface Sci. 121 (1988) 402] which is valid for kappa a >> 1 and zero frequency.

Electrically induced anisotropy in a colloidal dispersion of nanospheres as measured by electric birefringence.

Electrically induced birefringence experiments were performed on dispersions consisting of sulfate latex nanospheres of two different sizes and charges dispersed in an electrolyte solution, at various ionic strengths. The induced birefringence was found to have an important contribution increasing as a quadratic power law of the volume fraction of the spheres. This shows that interparticle interactions play a role in the observed birefringence. The data were analyzed, using a theory from Hafkenscheid and Vlieger [Physica 75 (1974) 57], in terms of the changes of the interparticle separations in the directions parallel and perpendicular to the applied electric field.

Primary cardiac Burkitt lymphoma in a child.

Primary cardiac lymphoma (PCL) is a rare and usually fatal malignancy, seldom reported in children. This report describes the case of a 10-year-old boy who presented with multiple intracardiac masses which, when biopsied, proved to be small non-cleaved cell (Burkitt's) lymphoma. The first two cycles of chemotherapy according to the LMB 96 protocol were given under close cardiological supervision, with good response. The treatment was then continued with full-dose chemotherapy, without any cardiological complication. The patient who was treated by chemotherapy alone remains in complete remission 36 months after the end of treatment and can presently be considered as cured, without late cardiac effect.

Relevance of intraocular involvement in the management of primary central nervous system lymphomas.

BACKGROUND: Reported data regarding intraocular lymphoma (IOL) management are anecdotal. Cases of IOL included in an international multicentre series of 378 immunocompetent patients with primary central nervous system lymphomas (PCNSLs) were reviewed. PATIENTS AND METHODS: Staging included slit-lamp examination in 170 patients: IOL was diagnosed in 22 cases (13%). A concomitant brain lesion was detected in 21 cases. Planned treatment was chemotherapy followed by radiotherapy in 13 cases, chemotherapy alone in three and radiotherapy, followed by or not by chemotherapy in five; one patient was not treated. Chemotherapy included high-dose methotrexate in 12 cases. Ten patients received intrathecal chemotherapy. Radiotherapy consisted of whole brain irradiation, followed by or not by a tumour bed boost; ocular irradiation was planned in 15 cases. Irradiation in one patient without brain lesions was limited to the orbits only (50 Gy). RESULTS: IOL was positively correlated to systemic symptoms and meningeal disease. Fifteen patients (71%) achieved an objective response; 16 patients experienced a failure (2-year failure-free survival 34+/-10%). Failures involved the eyes in eight cases, with a 2-year time to ocular relapse of 59+/-11%. Ocular failure was less common in patients treated with chemotherapy plus ocular irradiation and was associated with a significantly shorter survival. Seven patients are alive [median follow-up 53 months, 2-year overall survival (OS): 39+/-11%] , five of whom were treated with ocular irradiation. The patient with isolated IOL is alive and disease-free at 14 months. OS of the entire series was similar to that of PCNSL patients with negative slit-lamp examination. CONCLUSIONS: IOL is usually associated with concomitant brain disease and shows a survival similar to that of the rest of PCNSLs. Chemotherapy combined with ocular irradiation resulted in better control of ocular disease, which seems to be associated with survival. In view of the potential role of ocular irradiation, the use of chemotherapy alone in phase II trials should be critically reconsidered in PCNSL patients with ocular disease.

A multicenter study of treatment of primary CNS lymphoma.

OBJECTIVE: To characterize the therapeutic variables correlated to outcome in 370 patients with primary CNS lymphoma. METHODS: Planned treatment was radiotherapy (RT) in 98 patients, chemotherapy (CHT) in 32, RT followed by CHT in 36, and CHT followed by RT in 197 patients. High-dose methotrexate (HD-MTX; 1 to 8 g/m2) was used in 169 patients and intrathecal CHT in 109. RESULTS: One hundred sixteen patients are alive (median follow-up 24 months), with a 2-year overall survival of 37%. Patients treated with CHT followed by RT had improved survival with respect to patients treated with RT alone. Patients receiving HD-MTX-based primary CHT survived longer than those treated with other drugs. HD-MTX associated with other cytostatics, in particular HD-cytarabine, produced better results than HD-MTX alone. No correlation between MTX dose and survival was found. In patients receiving HD-MTX, consolidation RT or intrathecal CHT did not improve survival. Age, performance status, lactate dehydrogenase serum level, CSF protein level, site of disease, and use of HD-MTX were all predictors of survival. CONCLUSIONS: Combination CHT-RT is superior to RT alone. Patients treated with primary CHT containing HD-MTX exhibited improved survival. In these patients, the addition of HD-cytarabine was associated with a better survival, whereas intrathecal CHT was not correlated to outcome. RT may be unnecessary in patients achieving complete remission after receiving HD-MTX-based primary CHT.

The interpretation of dielectric spectroscopy measurements on silica and hematite sols.

Experimental data on the dielectric response of silica and hematite sols from the literature are interpreted using an analytical theory developed previously (Chassagne, C., Bedeaux, D., and Koper, G. J. M., J. Phys. Chem B105, 11,743 (2001), and Physica A, to be published). The theory is found to correctly predict both the relaxation frequency and the dielectric permittivity enhancement at low frequencies with only one free parameter. This parameter can be the zeta potential or the Stern layer conductance, in the case that the zeta potential is fixed to agree with the electrophoretic mobility measurements.

Non-Hodgkin's lymphoma of the testis: a retrospective study of 84 patients treated in the French anticancer centres.

Primary non-Hodgkin's lymphoma of the testicle is rare. We analysed cases treated in French anticancer centres from 1969 to 1995. All cases were reviewed and classified according to the R.E.A.L. Classification. Eighty-four cases were included in this study. The median age was 67 years (17-85). Disease was classified as stages I in 42 cases, stages II in 19 and stages III-IV in 23. Diffuse large B-cell lymphoma was diagnosed in 75% of cases. Treatment included orchidectomy and radiotherapy and/or chemotherapy. A complete response was obtained in 72.6% of the patient population and in 100%, 68% and 33% of stage I, II and III-IV disease respectively. Recurrence occurred in 32 cases and the most frequent site was the central nervous system: six of these patients presented stage I disease. Median overall survival was 32 months for the entire population, 52 months for stage I, 32 months for stage II, and 12 months for stage III-IV cases (P < 0.0001). Among patients presenting stage I disease, no difference was found between those treated with combined surgery and chemotherapy or surgery followed or not followed by radiotherapy. This study confirms that non-Hodgkin's lymphoma of the testicle carries a poor prognosis. Systemic adjuvant chemotherapy should be discussed because of the high recurrence rate. Inclusion of these cases in large co-operative prospective studies is recommended.

Lymphatic mapping and sentinel node biopsy of operable breast cancer.

The aim of this study was to evaluate the reliability and accuracy of sentinel node biopsy for invasive breast cancer and the predictability of axillary node status. Between January 1996 and June 1997 a total of 73 patients underwent patent blue dye lymphatic mapping and sentinel node biopsy followed by standard (level I and II) axillary node dissection (one bilateral procedure). The sentinel node was identified in 82.4% (61/74) of the cases and was predictive of axillary status in 96.7% (59/61). The false-negative rate of the procedure was 8.0% (2/25). The sentinel node was involved in 37.7% (23/61) and was the only one invaded in 30.4% (7/23). The sensitivity of the procedure was 92% (CI95% 74-99%) and its specificity 100%. It is currently considered to be an attractive new procedure undergoing evaluation in prospective controlled trials. This study confirmed the reliability and reproducibility of intraoperative lymphatic mapping and sentinel node biopsy. This is the first step toward a new era of minimally invasive axillary surgery for breast cancer.

Effect of pressure overload on angiotensin receptor expression in the rat heart during early postnatal life.

The development of cardiac hypertrophy during neonatal life and in adults implies different processes. The angiotensin II (Ang II) system is involved in the development of cardiac hypertrophy in adults, but its role in neonates remains unclear. The aim of this study was to estimate the influence of increased hemodynamic load on the developmental pattern of the AT1/AT2 receptor expression in the heart. Two-day-old rats submitted to abdominal aortic constriction (AC) or sham operation were sacrificed 2 h, and 1, 3, and 8 days after surgery. Ang II was evaluated in sera and immunohistology was performed to define the cardiac hypertrophy process. The Ang II receptor subtypes 1 and 2 were quantified at the receptor and mRNA levels by(125)I-Ang II binding and RT-PCR, respectively. Ang II content in sera increased transiently 2 h after surgery in the AC group. In sham-operated, AT1 and AT2 decreased throughout the period studied at both mRNA and receptor levels. However, the AT1 mRNA level decrease was more pronounced than that of AT2 (by 57% and 27%, respectively). AC not only prevented the postnatal decrease in AT mRNA level but resulted in an increase in AT1 mRNA 8 days after surgery (P<0.05). Besides in the AC groups, AT2 mRNA levels but not those of AT1 mRNA were linearly correlated with the left ventricular mass. At the receptor level, a significant transient (1 day after surgery) increase in both AT1 and AT2 was observed. In conclusion, our data demonstrated that imposition of pressure overload soon after birth altered the pattern of AT receptor expression.