Novel radiochemical separation of arsenic from selenium for 72Se/72As generator

A new radiochemical separation scheme based on extraction chromatography has been proposed for isolation of arsenic from selenium. The distribution coefficients of As and Se on prepared sorbents: (selected aromatic o-diamines supported on polystyrene adsorbents) were determined in order to find the best condition for separation of both the elements. Batch experiments were verified by column studies. This work, together with earlier results from this Laboratory, enabled to elaborate a new separation scheme for selective and quantitative separation of arsenic from selenium. Proposed approach insures high selectivity and radionuclide purity of separated arsenic fraction; it is also characterized by high elution efficiency (>95%) using small volume (2 mL) of 0.9% NaCl with very low breakthrough (<0.01%) of selenium.     

An isotope generator for 72As

⁷²Se has been produced by bombarding a thick target of natural germanium with 38.4 MeV ₂⁴He ions. The target was allowed to decay for three days to remove ⁷³Se. ⁷²Se was separated as elemental selenium and mounted on a column of cationic exchange resin. When ⁷²As had grown to equilibrium the column was warmed to 60°C and eluted with distilled water. Seventy per cent of the eluted arsenic was in the first three 5 ml fractions. No impurities could be detected in the gamma spectrum. The yield of ⁷²As was at least 60%.     

Rhenium-188: availability from the (188)W/(188)Re generator and status of current applications

Rhenium-188 is one of the most readily available generator derived and useful radionuclides for therapy emitting β(-) particles (2.12 MeV, 71.1% and 1.965 MeV, 25.6%) and imageable gammas (155 keV, 15.1%). The (188)W/(188)Re generator is an ideal source for the long term (4-6 months) continuous availability of no carrier added (nca) (188)Re suitable for the preparation of radiopharmaceuticals for radionuclide therapy. The challenges associated with the double neutron capture route of production of the parent (188)W radionuclide have been a major impediment in the progress of application of (188)Re. Tungsten-188 of adequate specific activity can be prepared only in 2-3 of the high flux reactors operating in the World. Several useful technologies have been developed for the preparation of clinical grade (188)W/(188)Re generators. Since the specific activity of (188)W used in the generator is relatively low 185 GBq( < 5 Ci)/g], the eluted (188)ReO(4)(-) can have low radioactive concentration often insufficient for radiopharmaceutical preparation. However, several efficient post elution concentration techniques have been developed that yield clinically useful (188)ReO(4)(-) solutions. Rhenium-188 has been used for the preparation of therapeutic radiopharmaceuticals for the management of diseases such as bone metastasis, rheumatoid arthritis and primary cancers. Several early phase clinical studies using radiopharmaceuticals based on (188)Re-labeled phosphonates, antibodies, peptides, lipiodol and particulates have been reported. This article reviews the availability and use of (188)Re including a discussion of why broader use of (188)Re has not progressed as expected as a popular radionuclide for therapy.     

Selenium-72 formation via Br(p,x) induced by 100 MeV Protons: Steps towards a novel Se/As generator system

Selenium-72 production by the proton bombardment of a natural NaBr target has been successfully demonstrated at the Los Alamos National Laboratory Isotope Production Facility (LANL-IPF). Arsenic-72 (half life 26 h) is a medium-lived positron emitting radionuclide with the major advantage of being formed as the daughter of another “generator” radioisotope (Se-72, 8.5 d). A ⁷²Se/⁷²As generator would be the preferred mechanism for clinical utilization of ⁷²As for positron emission tomography (PET). No portable ⁷²Se/⁷²As generator system has been demonstrated for convenient, repeated ⁷²As elution (“milking”). In this work, we describe ⁷²Se production and recovery from irradiated NaBr targets using a 100 MeV proton beam. We also introduce an ⁷²As generator principle based on ⁷²Se chelation followed by liquid-liquid extraction, which will be transferred to a solid-phase sorption/elution system.     

Scandium-44: benefits of a long-lived PET radionuclide available from the (44)Ti/(44)Sc generator system

(44)Ti/(44)Sc radionuclide generators are of interest for molecular imaging. The 3.97 hours half-life of (44)Sc and its high positron branching of 94.27% may stimulate the application of (44)Sc-labeled PET radiopharmaceuticals. This review describes the current status of (44)Ti production, (44)Ti/(44)Sc radionuclide generator development, post-processing of generator eluates towards medical application, identification of ligands adequate to Sc(III) co-ordination chemistry, proof-of-principle labeling of (44)Sc-DOTA-octreotides, investigation of in vitro and in vivo parameters, and initial applications for molecular imaging - both in small animals and humans.     

Preparation of (166)Dy/(166)Ho-EDTMP: a potential in vivo generator system for bone marrow ablation

BACKGROUND AND AIM: Bone-seeking radiopharmaceuticals have been proposed for delivering ablative radiation doses to marrow in multiple myeloma and other haematological malignancies. The aim of this research was to examine the feasibility of labelling ethylenediaminetetramethylenephosphonate (EDTMP) with Dy/Ho as an in vivo generator system and to evaluate whether the in vitro and in vivo stability of Dy-EDTMP and Ho-EDTMP complexes is maintained when the daughter Ho is formed. METHODS: Dy was obtained by neutron irradiation of enriched Dy2O3 in a TRIGA Mark III reactor. Labelling was carried out in an aqueous phosphate medium at pH 8.0 by addition of DyCl3 to EDTMP at a molar ratio 1:1.75. Dy/Ho labelled EDTMP was obtained with a 99.3+/-0.6% radiochemical purity determined by thin-layer chromatography and high-performance liquid chromatography. RESULTS: In vitro studies demonstrated that Dy/Ho-EDTMP is unstable after dilution in saline and stable in human serum and no translocation of the daughter nucleus occurring subsequent to beta decay of Dy which could produce release of Ho. Biodistribution in mice shows a fast blood clearance after administration of Dy/Ho-EDTMP with a skeletal uptake of 22.32+/-1.86% ID/g at 2 h and 20.12+/-1.94% ID/g after 10 d, a rapid renal elimination and no accumulation in other organs. Theoretical bone marrow absorbed dose calculations indicate that the Dy/Ho-EDTMP in vivo generator system would produce 7.80 times more radiation dose to marrow than that produced by Sm-EDTMP and 3.47 times more than Ho-DOTMP per unit of initial activity retained in the skeleton. CONCLUSION: The prepared radiolabelled EDTMP has adequate properties as a stable in vivo generator system for bone marrow ablation.     

A possible in vivo generator (103)Pd/(103m)Rh-Recoil considerations.

The use of Auger emitters as potential radiopharmaceuticals is increasingly investigated. One such radionuclide of interest is (103m)Rh. This can be produced from (103)Ru or from (103)Pd in an in vivo generator. A potential problem with this concept is the recoil of the (103m)Rh out of the carrier molecule and even out of the target cell. In order to determine whether this would happen in the (103)Pd/(103m)Rh case calculations were done to prove that this does not happen. From theoretical considerations it seems that the (103)Pd/(103m)Rh in vivo generator system would be possible.     

Use of (99m)Tc from a commercial (99)Mo/(99m)Tc generator as yield tracer for the determination of (99)Tc at low levels.

The concentrations of (99)Tc and impurity radionuclides in the (99m)Tc tracer solution obtained from a commercial (99)Mo/(99m)Tc generator were measured by gamma spectrometry and liquid scintillation counting. (99)Mo and (103)Ru were found in the (99m)Tc eluate. A simple separation using two extra alumina cartridges was investigated to purify the eluate to obtain a suitable (99m)Tc tracer with low (99)Tc concentration. The activity ratio of (99)Tc/(99m)Tc in the prepared (99m)Tc solution is lower than 15 x 10(-9), which is higher than the theoretical ratio of less than 10 x 10(-9). The possible reason is discussed. The (99)Tc in the 20 kBq spiked (99m)Tc tracer was found to be less than 0.3 mBq, which is lower than the detection limit of the radiometric method used for environmental samples. The purified (99m)Tc eluate is used as yield tracer for the determination of low levels of (99)Tc in environmental samples.     

Validation of (68)Ge/(68)Ga generator processing by chemical purification for routine clinical application of (68)Ga-DOTATOC

INTRODUCTION: Imaging of somatostatin receptor expressing tumours has been greatly enhanced by the use of (68)Ga-DOTATOC and PET/CT. METHODS: In this work, a purification method for the (68)Ge/(68)Ga generator eluate and a method to produce (68)Ga-DOTATOC suitable for clinical use were evaluated. The generator eluate was purified and concentrated on a cation-exchange cartridge in HCl/acetone media. The efficacy of this procedure in eliminating metal impurities from the (68)Ga solution was investigated by ICP-MS. The radiotracer quality was evaluated by radio-TLC, GC and gamma-ray spectrometry. RESULTS: (68)Ga-DOTATOC preparations (n=33) were carried out with a mean synthesis yield of 59.3+/-2.8% (not corrected for decay) and a batch activity ranging from 555 to 296 MBq. The radiochemical and radionuclidic purity were >98% and 99.9999%, respectively. With this purification process, >95% of the Fe(III), Zn(II) and Mn(II) were eliminated from the solution. CONCLUSIONS: (68)Ga-DOTATOC produced with this method can be efficiently used in nuclear medicine departments for PET evaluations.     

Excitation functions of natGe(p,xn)71,72,73,74 As reactions up to 100 MeV with a focus on the production of 72 As for medical and 73 As for environmental studies.

Excitation functions for the formation of the arsenic radionuclides (71)As, (72)As, (73)As and (74)As in the interaction of protons with (nat)Ge were measured from the respective threshold energy up to 100 MeV. The conventional stacked-foil technique was used and the needed thin samples were prepared by sedimentation. Irradiations were done at three cyclotrons: CV 28 and injector of COSY at Forschungszentrum Jülich, and Separate Sector Cyclotron at iThemba LABS, Somerset West. The radioactivity was measured via high-resolution gamma-ray spectrometry. The measured cross section data were compared with the literature data as well as with the nuclear model calculations. In both cases, the results generally agree but there are discrepancies in some areas, the results of nuclear model calculation and some of the literature data being somewhat higher than our data. The integral yields of the four radionuclides were calculated from the measured excitation functions. The beta(+) emitting nuclide (72)As (T(1/2)=26.01 h) can be produced with reasonable radionuclidic purity ((71)As impurity: <10%) over the energy range E(p) = 18-->8 MeV; the yield of 93 MBq/microAh is, however, low. The radionuclide (73)As (T(1/2)=80.30 d), a potentially useful indicator in environmental studies, could be produced with good radionuclidic purity ((74)As impurity: <11%) over the energy range E(p) = 30 --> 18 MeV, provided, a decay time of about 60 days is allowed. Its yield would then correspond to 2.4 MBq/microAh, and GBq amounts could be produced when using a high current target.     

Three-dimensional visualization and analysis methodologies: a current perspective.

Three-dimensional (3D) imaging was developed to provide both qualitative and quantitative information about an object or object system from images obtained with multiple modalities including digital radiography, computed tomography, magnetic resonance imaging, positron emission tomography, single photon emission computed tomography, and ultrasonography. Three-dimensional imaging operations may be classified under four basic headings: preprocessing, visualization, manipulation, and analysis. Preprocessing operations (volume of interest, filtering, interpolation, registration, segmentation) are aimed at extracting or improving the extraction of object information in given images. Visualization operations facilitate seeing and comprehending objects in their full dimensionality and may be either scene-based or object-based. Manipulation may be either rigid or deformable and allows alteration of object structures and of relationships between objects. Analysis operations, like visualization operations, may be either scene-based or object-based and deal with methods of quantifying object information. There are many challenges involving matters of precision, accuracy, and efficiency in 3D imaging. Nevertheless, 3D imaging is an exciting technology that promises to offer an expanding number and variety of applications.     

Vein of Galen aneurysms: a review and current perspective.

Our approach to treating a patient with a vein of Galen aneurysm is, of course, influenced greatly by the age of the patient, the clinical symptoms, and the angiographic architecture of the malformation. Therapeutic options are primarily based on whether a true AVM is present or if the malformation represents an arteriovenous fistula involving the vein of Galen. Arterial endovascular approaches, microneurosurgery, and/or radiosurgery are preferred for management of the former; the transvenous endovascular approach has become the cornerstone of treatment in the latter. The most critical group, however, is the neonates in extreme cardiovascular distress. In this case our therapeutic intervention is initially endovascular from the venous side, either transfemoral or transtorcular. The immediate goal is to increase resistance to right ventricular output. Advantages of this approach over a transarterial approach include a shorter anesthesia time, minimal fluid and/or contrast administration, and creation of a wire "basket" or "bird''s nest" on the venous side that helps prevent emboli that may be deposited on the arterial side in subsequent embolizations from passing through the malformation. The transvenous approach can be easily repeated multiple times and may be supplemented by transarterial embolizations. Endovascular coils have been the mainstay for such venous embolizations. The end point of treatment is not complete occlusion of the fistula but improvement in cardiac function. Often, more than one stage is required to reach our goal. The results in recent years have been encouraging and are to a large degree attributable to the advances in endovascular approaches. With future improved tools for diagnosis and treatment, perhaps the prognosis for this difficult malady also will continue to improve.     

Physiology of handcycling: A current sports perspective

Handcycling is a mode of mobility, and sport format within Para‐cycling, for those with a lower limb impairment. The exercise modality has been researched extensively in the rehabilitation setting. However, there is an emerging body of evidence detailing the physiological responses to handcycling in the competitive sport domain. Competitive handcyclists utilize equipment that is vastly disparate to that used for rehabilitation or recreation. Furthermore, the transferability of findings from early handcycling research to current international athletes regarding physiological profiles is severely limited. This narrative review aims to map the landscape within handcycling research and document the growing interest at the elite end of the exercise spectrum. From 58 experimental/case studies and four doctoral theses, we provide accounts of the aerobic capacity of handcyclists and the influence training status plays; present research regarding the physiological responses to handcycling performance, including tests of sprint performance; and discuss the finite information on handcyclists’ training habits and efficacy of bespoke interventions. Furthermore, given the wide variety of protocols employed and participants recruited previously, we present considerations for the interpretation of existing research and recommendations for future work, all with a focus on competitive sport. The majority of studies (n = 21) reported aerobic capacity, detailing peak rates of oxygen uptake and power output, with values >3.0 L min^?1 and 240 W shown in trained, male H3‐H4 classification athletes. Knowledge, though, is lacking for other classifications and female athletes. Similarly, little research is available concerning sprint performance with only one from eight studies recruiting athletes with an impairment.     

(68)Ga-BPAMD: PET-imaging of bone metastases with a generator based positron emitter

PurposeBone metastases are a serious aggravation for patients suffering from cancer. Therefore, early recognition of bone metastases is of great interest for further treatment of patients. Bisphosphonates are widely used for scintigraphy of bone lesions with ^99mTc. Using the ⁶⁸Ge/⁶⁸Ga generator together with a macroyclic bisphosphonate a comparable PET-tracer comes into focus.ProceduresThe bisphosphonate DOTA-conjugated ligand BPAMD was labelled with ⁶⁸Ga. [⁶⁸Ga]BPAMD was evaluated in vitro concerning binding to hydroxyapatite and stability. The tracer's in vivo accumulation was determined on healthy rats and bone metastases bearing animals by μ-PET.ResultsBPAMD was labelled efficiently with ⁶⁸Ga after 10 min at 100 °C. [⁶⁸Ga]BPAMD showed high in vitro stability within 3 h and high binding to hydroxyapatite. Consequently, μ-PET experiments revealed high accumulation of [⁶⁸Ga]BPAMD in regions of pronounced remodelling activity like bone metastases.Conclusions⁶⁸Ga BPAMD reveals great potential for diagnosis of bone metastases via PET/CT. The straight forward ⁶⁸Ga-labelling could be transferred to a kit-preparation of a cyclotron-independent PET tracer instantaneously available in many clinical sites using the ⁶⁸Ge/⁶⁸Ga generator.     

Validation of a new portable ergospirometric device (Oxycon Mobile) during exercise

The purpose of this study was to test the accuracy of a new portable spirometric-telemetric device (Oxycon Mobile) over a wide range of exercise intensities against an accurate stationary apparatus (Oxycon Pro). Therefore, fifteen endurance-trained subjects (VO2peak: 58.8 +/- 5.2 ml x min(-1) x kg(-1)) performed an incremental as well as an endurance exercise test on two different occasions. Gas exchange variables were measured by the two ergospirometric devices simultaneously. For this purpose, a special face mask was designed which allowed respiratory gas sampling with both devices at exactly the same time. Compared to the Oxycon Pro as an accurate reference system, the Oxycon Mobile showed significantly lower values for VO2 at 200 and 250 W during the incremental exercise test. For VCO2 no significant differences were found although the Oxycon Mobile seemed to systematically measure higher values. With regard to RER the Oxycon Mobile showed significantly higher values at all workloads tested. We therefore dissuade from comparing gas exchange variables collected by the Oxycon Mobile with data measured under laboratory conditions by an accurate reference system like the Oxycon Pro. Furthermore, the extrapolation of information about substrate utilization during different exercise durations and intensities from data measured by the Oxycon Mobile seems inappropriate.     

A methodology to assess the accuracy of a portable metabolic system (VmaxST)

PURPOSE: Validity of a portable metabolic system (VmaxST) was investigated during gas exchanges simulations by a mechanical system (GESS) and during human exercise. METHODS: Three tests were conducted while gas exchanges were measured continuously by VmaxST. Test 1 was composed of six simulations of gas exchanges during steady-state exercise (20 min at [OV0312]E = 80 L.min-1). Test 2 was composed of seven simulations of gas exchanges during incremental exercise ([OV0312]O(2) from 300 to 5600 mL.min-1). In the human trial, 11 subjects performed an incremental running exercise on a treadmill while gas exchanges were measured at the end of each stage with the Douglas bag method (DBM). RESULTS: Test 1 showed that the VmaxST measurements were stable, despite inaccurate measurements of gas concentrations at the start of the test. During test 2, the mean error (difference between measured and predicted value) and the upper and lower limits of agreement were -8.0%, -12.6%, and -3.4% for [OV0312]O(2); -4.6%, -12.0%, and +2.8% for [OV0312]CO(2); and -0.7%, -4.7%, and +3.3% for [OV0312]E. During the human trial, no significant difference was shown between [OV0312]O(2) measured by VmaxST and by DBM at any stage of exercise. The mean difference and the upper and lower limits of agreement between the VmaxST and the DBM measurements were -0.5%, -14.3%, and +13.3% for [OV0312]O(2); -6.3%, -20.9%, and +8.3% for [OV0312]CO(2); and -9.9%, -25.5%, and +5.7% for [OV0312]E. CONCLUSIONS: The use of GESS showed that measurements of [OV0312]O(2) by VmaxST could be biased in a standardized condition. In more realistic condition of use, this bias was lower but the accuracy of measurements was impaired.