Volume 92, Issue 4-6 - Stöcklin Memorial Issue

The rise and fall of hot atom chemistry (HAC) over the years from 1934 to 2004 is reviewed. Several applications are discussed, in particular to astrophysics and the interaction of energetic ions and atoms in space. Epithermal chemistry (ETC) is proposed to substitute the old name, since it better fits the energy range as well as the non-thermal and non-equilibrium character of the reactions. ETC also avoids the strong connexion of HAC to nuclear chemistry and stands for the opening of the field to physical chemistry and astrophysics.

Excitation functions of the 78 Kr(d,α) 76 Br, 78 Kr(d,n) 79 Rb and 78 Kr(d,x) 79 Kr reactions were measured for the first time in the energy range up to 13 MeV using the stacked gas cell technique and activation method. Highly enriched 78 Kr was used as target material. The maximum cross section of the 78 Kr(d,α) 76 Br reaction at 13 MeV amounts to 21 mb and the calculated yield of 76 Br over the energy range E d =13→4 MeV to only 59 kBq/μA h. Due to the very low expected yield of 76 Br and the high cost of the target gas, this route is not suitable for production of 76 Br compared with the other well investigated production routes.

Copper-61 (T 1/2 =3.41 h) produced via the 59 Co(α,2n) 61 Cu nuclear reaction using natural Co target was isolated from the irradiated target by two methods developed here and applied for preparation of ( 61 Cu-ATSM) ( 61 Cu-diacetyl-bis(N 4 -methylthiosemicarbazone)), known as an imaging agent of hypoxic tissue. A commercially available cobalt disk (thickness: 125 μm) was irradiated with 40 MeV (37.9 MeV on target) α particles, then treated with conc. HNO 3 , and the 61 Cu was separated by two different methods, i.e. a two column method using a cation and an anion exchange column; and a one column method using a column packed with chelating resin, Chelex 100. Both separation methods gave satisfactory results, though the latter method was superior because of the simplicity of the apparatus, the separation procedure and somewhat shorter processing time. Around 1.1 GBq of 61 Cu 2+ were obtained with >95% yield (decay corrected) from Co target at 10 μA for 1 h irradiation, and with the radionuclidic purity of >98% (EOS). The only radionuclidic impurity in the isolated 61 Cu 2+ solution was identified to be 60 Cu at EOS but no radionuclidic impurity was observed after 50 hours. The solution of 61 Cu-ATSM was prepared in >85% radiochemical yield with >95% radiochemical purity.

Proton and deuteron induced nuclear reactions for generation of the 103 Pd parent 103 Ag were investigated using the stacked-foil activation technique on natural palladium targets up to E p =37.3 MeV and E d =20.5 MeV, respectively. Excitation functions are reported for the first time for the reactions nat Pd(p,xn) 103 Ag and nat Pd(d,xn) 103 Ag.

The lanthanide isotope 165 Er decays by electron capture without any accompanying gamma radiation, which makes it an ideal radionuclide for Auger electron therapy. The chemical properties of erbium with regard to labelling of bio-conjugates are virtually identical to those of radio-yttrium. We measured the excitation function of the 165 Ho(p,n) 165 Er reaction and obtained a maximum cross section of 166±20 mb at 11.1±0.5 MeV proton energy. Our findings indicate that 165 Er can be produced at any small-sized cyclotron in quantities suitable for biomedical applications. The thick target yield at E p =15 MeV is 55 MBq/μA h. A mass separated sample of the nuclide pair 160 Er/ 160 Ho was used as model to demonstrate that the separation of the 165 Er from the target matrix material Ho can be achieved by cation-exchange chromatography using Aminex A5 resin and α-HIBA as eluent in about 1 hour.

The possible production of the therapeutic radioisotopes 198 Au and 199 Au using charged particle reactions at cyclotrons was investigated. For the first time, excitation functions for the 198 Pt(p,n) 198g Au, 198 Pt(d,2n) 198m,g Au and 198 Pt(d,x) 199 Au nuclear reactions were measured up to 40 MeV proton and 20 MeV deuteron energies. The results were compared with calculations performed with the computer code ALICE-IPPE. Acceptable overall agreement was obtained. Production and product quality parameters are discussed on the basis of the measured cross sections and from the deduced integral yields.

A convenient source of -7 second [ 16 N]-N 2 is described, employing the deuteron irradiation of a flow-through nitrogen target, suitable for the calibration of gamma detectors to 7 MeV and beta spectrometers to 10 MeV. Its possible presence as a contaminant in 15 O-gases bears watching.

We report a new half-life value of 205 Bi. During measurements of cross sections for the production of residual radionuclides in proton-induced reactions on lead and bismuth a discrepancy was recognised between the published half-life of 205 Bi and our experimental results. In this work, the value for the half-life of 205 Bi was determined to be (14.91±0.07) days, based on measurements on 33 irradiated lead samples.

Generator nuclides constitute a convenient tool for applications in nuclear medicine. In this paper, some radiochemical aspects of generator nuclide parents regularly processed at Los Alamos are introduced. The bulk production of the parent nuclides 68 Ge, 82 Sr, 109 Cd and 88 Zr using charged particle beams is discussed. Production nuclear reactions for these radioisotopes, and chemical separation procedures are presented. Experimental processing yields correspond to 80%-98% of the theoretical thick target yield. Reaction cross sections are modeled using the code ALICE-IPPE; it is observed that the model largely disagrees with experimental values for the nuclear processes treated. Radionuclide production batches are prepared 1-6 times yearly for sales. Batch activities range from 40 MBq to 75 GBq.

Arsenic-72 is a positron emitting isotope with promising properties for syntheses of 72 As-labelled radiopharmaceuticals for future application in positron emission tomography. This work describes the radiochemical separation of no-carrier-added 72 Se from cyclotron irradiated germanium targets and the development of a 72 Se/ 72 As radionuclide generator, avoiding the addition of any selenium carrier. Using a vertical quartz tube device, no-carrier-added 72 As is nearly quantitatively released from various chloride salt solutions containing 72 Se within 10 min at a temperature of 100 °C in an HCl gas flow. The kinetics of the 72 Se/ 72 As isotope generator has been studied in relation to temperature, salt charge, and redox-stability. Under optimised conditions, 72 Se remains almost quantitatively (>99.7%) in solution.

Molybdenum-99 is an important radionuclide which is used in nuclear medicine and a new method is presented for the isolation and purification of 99 Mo from fission material. The method was developed to suit the needs of the Nuclear Energy Corporation of South Africa (NECSA) and also because most other methods had been patented and could therefore not be used at NECSA. A uranium-aluminium alloy, cladded in aluminium, served as a target and the target was irradiated in a nuclear reactor for several days. After a cooling period, in order to let the short-lived radionuclides decay, the target material was dissolved in a sodium hydroxide solution. The radioactive krypton and xenon gases were collected on activated carbon and stored until both gases had decayed. Aluminium, 99 Mo, 131 I and the radionuclides of alkali-soluble elements in the sodium hydroxide solution were separated from the uranium and radionuclides of the alkaline-insoluble elements by filtration. The radionuclides of molybdenum and iodine were separated by anion exchange chromatography, in alkaline medium, from the bulk aluminium and radionuclides of other elements, such as barium, strontium and tellurium. 99 Mo was selectively eluted with a slightly alkaline lithium sulphate solution, leaving the iodine radionuclides on the resin. The 99 Mo eluant was acidified with oxalic acid and nitric acid and 99 Mo separated from the remaining aluminium and other radionuclides by anion exchange chromatography, in acid medium. After elution of 99 Mo, again with a slightly alkaline lithium sulphate solution, the eluant was acidified with nitric acid, 99 Mo concentrated on a chelating resin column and finally eluted with ammonia and evaporated to obtain 99 MoO 3 which was then dissolved in diluted sodium hydroxide solution. The purity of the final product was within the specifications of the British and European Pharmacopoiea and no further purification steps, such as sublimation, were required.

The effect of subtle variations on zirconium molybdate- 99 Mo gel preparatory conditions, such as stoichiometry of reactants, pH of gel formation, conditioning of gel granules etc. , prior to elution were investigated primarily to arrive at the conditions resulting in high 99m Tc release and minimal 99 Mo breakthrough upon elution with normal saline. Zirconium molybdate- 99 Mo gels were prepared by reacting solutions of Zr and Mo in mole ratios of 0.75-1.5. Both water and normal saline were used for gel disintegration, and the release of 99m Tc and 99 Mo from gel columns into eluates was compared. Sharper elution profile of 99m Tc, but with significantly higher 99 Mo breakthrough (5-8 times), was obtained when water alone was used for disintegration and elution, in comparison to when saline was used. Gels exhibiting optimum characteristics were found to be formed at a pH of 4-5 by reacting [Zr]:[Mo] in the mole ratio of 1.25:1 and after drying, the product was dispersed into granules by disintegration with normal saline. 99m Tc elution efficiency was found to be ∼75% and 99 Mo breakthrough ∼0.05%. The elution profile was sharp when a 6 g gel column coupled to a 2 g acidic alumina column (to trap 99 Mo) was eluted with 6-9 ml normal saline. Generators containing upto 23 GBq 99 Mo were prepared, eluted extensively without changing the alumina column and found to provide pertechnetate of good quality, commensurate with hospital radiopharmacy requirements.

A novel nitridotechnetium(V) complex with a tetradentate Schiff base ligand, TcN(bzdbsalpn), was synthesized by the reaction of TcNCl 2 (PPh 3 ) 2 and N , N ´-bis(3,5-di- t -butyl-salicylidene)-2-benzyl-1,3-propanediamine (H 2 bzdbsalpn). Both the syn - and anti -isomers of TcN(bzdbsalpn) were formed in the solution, but recrystallization of a mixture of syn - and anti -TcN(bzdbsalpn) gave a single crystal only for the syn -isomer. X-ray crystallography showed that the syn -TcN(bzdbsalpn) was in a distorted octahedral structure. The planar tetradentate bzdbsalpn ligand coordinates to the technetium atom in an O-N-N-O equatorial plane and the six-membered N imine -N imine chelate ring that includes the propylene group adopts a chair conformation. The nitrido ligand (Tc≡N) is at an apical position and the Tc≡N triple bond length is 1.6 Å. Interestingly, the crystal of syn -TcN(bzdbsalpn) has a nitrido-bridged linear polymeric structure (···Tc≡N···Tc≡N···) running along the 2 1 screw axes parallel to the b axis. The intermolecular N···Tc distance in the syn -TcN(bzdbsalpn) crystal (∼2.8 Å) is fairly long compared with that reported for Cr(V) and Mn(V) nitrido complexes with analogous Schiff base ligands (∼2.5 Å).

Bifunctional ligands able to form neutral complexes with radioactive technetium and rhenium and to couple to biological relevant anchor groups play an important role in the design of new radiopharmaceuticals for diagnosis and therapy. A novel tetradentate amide thioether dithiolate ligand HS-CH 2 CH 2 -S-CH 2 CONH-CH(COOR)CH 2 SH (H 3 SNSS) with R=CH 3 , C 10 H 21 was synthesized that forms stable complexes with technetium and rhenium in oxidation state V. The molecular structures of the rhenium and technetium complexes MO(SNSS) were determined by X-ray structural analysis and show that the metal coordination number is five and the coordination polyhedron is between square-pyramidal and trigonal-bipyramidal. The pendent ester group allows coupling of the chelate unit at biologically relevant anchor groups. As a relevant representative the X-ray structural analysis of the rhenium decylester complex was carried out. The complex formation with Tc at the n.c.a. level and 186 Re at 10 -6 M level is described.

The pentavalent rhenium-188 meso-dimercaptosuccinic acid complex 188 Re(V)-DMSA is a beta-emitting analogue of Tc99 m (V)-DMSA, an established tracer that is taken up in a variety of histological different tumors and especially in bone metastases arising from breast and prostate carcinomas. The similar general biodistribution and tumor avidity of 188 Re- and 99m Tc(V)-DMSA therefore suggests the use of the rhenium analog as an agent for therapeutic applications. No-carrier-added 188 Re(V)-DMSA is composed of a mixture of three stereoisomers arising from different orientations of the 4 carboxylate groups of the complex. For therapeutic applications it must be known whether there is a difference in the in-vivo biodistribution and kinetics of the individual stereo isomers. The aim of this study was therefore a) to characterize the chemical stability of each of the 3 stereoisomers with respect to time, temperature and pH and b) to evaluate if there are differences in the in-vivo organ distribution of the pure isomers compared to the isomeric mixture. The in-vitro results revealed for all three individual isomers of 188 Re(V)-DMSA a rather slow (with respect to half-life of Re-188) temperature and pH dependent rate of interconversion which would justify the application of pure isomers. The data obtained from urine samples of rats showed a faster interconversion rate and reached a stable isomer distribution after about six to ten hours, depending on which isomer was injected. However there was no evidence for isomer specific excretion rates. The organ biodistribution patterns of all three isomers were very similar at all times studied (10 min up to 24 hours p.i). The tumor uptake in a rat mammary carcinoma model at 1 hour p.i. did also not show any significant differences. In conclusion the preparation and administration of pure stereoisomers of 188 Re-DMSA is possible, however, in-vivo no significant differences in organ distribution and kinetics were observed which would favour the use of purified stereo isomers over the isomeric mixture of 188 Re(V)-DMSA.

High performance liquid chromatography (anion-exchange, reversed-phase ion-pair and gel permeation chromatography) and ultrafiltration have been employed to analyze 188 Re-ethylenediamine-N,N,N´,N´-tetrakis(methylenephosphonic acid) complexes ( 188 Re-EDTMP), prepared from the tin chloride reduction or sodium borohydride reduction in the presence or absence of rhenium carrier. The HPLC analysis showed that the 188 Re-EDTMP complexes were mixtures of components and the distribution of the components was dependent upon the total amount of rhenium present and the reducing agents (SnCl 2 , NaBH 4 ). The ultrafiltration analysis showed that the distribution of nominal molecular weight of 188 Re-EDTMP was dependent upon the presence of rhenium carrier and the reducing agents. In addition, it was found that the proportion of chemical species with bigger molecular weight in no-carrier-added 188 Re(SnCl 2 )-EDTMP was larger than that in carrier-added 188 Re(SnCl 2 )-EDTMP.

The PET radionuclide 76 Br (t 1/2 =16.2 h) can be easily produced utilizing the nuclear reaction As( 3 He,2n) 76 Br. We use high-purity arsenic targets and isolate radioactive bromide by chromic acid oxidation followed by simple distillation of [ 76 Br] hydrogen bromide using a semi-remote apparatus. Use of reagents with little or no carrier bromine yields high specific activity radiobrominated pharmaceuticals prepared from the distilled [ 76 Br] hydrogen bromide.

Metomidate [(R)-1-(1-phenylethyl)-1 H -imidazole-5-carboxylic acid methyl ester] (MTO, 1, Fig. 1) is a potent and selective inhibitor of the cytochrome P-450 enzyme system in the adrenal cortex. Labelled in the 4-position with radioiodine, (R)-4-[ 131 I]iodometomidate, 2, [ 131 I]IMTO has been evaluated by in-vitro studies and also ex-vivo in rats. [ 131 I]IMTO was synthesized by oxidative radioiododestannylation using a suitable precursor which was prepared by a new stereoselective synthesis. Optimization of the labelling reaction was performed by systematic variation of the most important reaction parameters. Under optimum reaction conditions, a labelling yield of 95% was obtained. In-vitro -stability of the tracer was studied over 8 days, indicating slow deiodination (0.27%/h). Displacement studies using [ 131 I]IMTO and rat adrenal membranes revealed the structural requirements for high affinity binding, namely an intact ester group and (R)-configuration of the radioligand. Pharmacokinetic studies in rats showed fast accumulation of [ 131 I]IMTO in the adrenals (approx. 10% ID/g tissue) with an activity plateau for 2 hours. Metabolic degradation was indicated by a steady increase of renal activity up to 4 hours post injection. Based on target to non-target ratios the highest contrast for imaging of the adrenals was observed between 30 and 60 min post injection of [ 131 I]IMTO. We conclude that SPECT using [ 123 I]IMTO will be a promising method for the characterization of adrenal incidentalomas.

The pyridazines 3-acetamidomethyl-6-chloro-2-(4´-iodophenyl)imidazo[1,2-b]pyridazine 1 (IC 50 =1.6 nM) and 3-benzamidomethyl-6-iodo-2-(4´-t-butylphenyl)imidazo[1,2-b] pyridazine 2 (IC 50 =4.2 nM), are high affinity and selective ligands for the Peripheral Benzodiazepine Receptors (PBR) compared to the Central Benzodiazepine counterparts. The [ 123 I] 1 and [ 123 I] 2 labelled analogues of these compounds were subsequently synthesised for the potential study of the PBR in vivo using SPECT. Radioiodination of [ 123 I] 1 was achieved by iododestannylation of the corresponding tributyl tin precursor with Na[ 123 I] in the presence of peracetic acid or chloramine-T and the product isolated by C-18 RP HPLC. Radioiodination of [ 123 I] 2 was achieved by copper assisted bromine [ 123 I]iodine exchange of the corresponding bromo precursor in the presence of acetic acid and sodium bisulfate as reducing agent at 200 °C. Purification of the crude products were achieved by semi-preparative C-18 RP HPLC to give the products in radiochemical yields >90%. The products were obtained in >97% chemical and radiochemical purity and with specific activities >180 GBq/μmol.

The aim of this study was to investigate the use of electrophilic radioiodination in the labelling of closo -monocarborane(-1). Ammonio- closo -monocarborane (ACMC, 1NH 3 1CB 11 H 11 ) was labelled with 125 I using Chloramine-T as an oxidant. Radio-TLC was used for analysis. Influence of substrate amount, oxidant concentration, and pH of the reaction media on the labelling yield was studied. A labelling yield of 80%-90% was obtained. The results of the study indicate feasibility to use derivatives of closo -monocarborane(-1) as a pendant group for indirect radioiodination of proteins, and for studying pharmacokinetics of boron-rich compounds for BNCT.

As part of our ongoing efforts in the development of new 18 F-labeled peptides for clinical PET imaging, a new two-step 18 F-labeling methodology based on the chemoselective oxime formation between an unprotected aminooxy-functionalized peptide and a 18 F-labeled aldehyde was investigated and optimized. 4-[ 18 F]Fluorobenzaldehyde ([ 18 F]FB-CHO) was prepared by direct n.c.a. fluorination of 4-formyl-N,N,N-trimethylanilinium triflate and purified by radio-HPLC or a strong-cation-exchange/reverse phase cartridge system. The aminooxyacetic acid (Aoa) modified model peptide LEF-NH 2 (Leu-Glu-Phe-NH 2 ) and monomeric, dimeric and tetrameric RGD-containing cyclopeptides were synthesized by solid phase peptide synthesis. Radiochemical yields of N-(4-[ 18 F]fluorobenzylidene)-oxime-formation ([ 18 F]FBOA) with the Aoa-modified unprotected peptides were investigated. Optimized reaction conditions (60 °C, 0.5 mM peptide, 15 min, aqueous solution, pH 2.5) resulted in 70%-90% conjugation yields for all unprotected peptides studied. Chemoselectivity was demonstrated in competition experiments with amino acid mixtures. Biodistribution in M21 melanoma bearing mice showed improved tumor uptake and excretion behaviour in the series c(RGDfE)HEG-Dpr-[ 18 F]FBOA < (c(RGDfE)HEG) 2 K-Dpr-[ 18 F]FBOA < ((c(RGDfE)HEG) 2 K) 2 K-Dpr-[ 18 F]FBOA. Two hours p.i. the fraction of intact c(RGDfE)HEG-K-Dpr-[ 18 F]FBOA in blood, liver, kidney and tumor was >90%, indicating high in vivo stability of the oxime linkage. Initial PET studies with ((c(RGDfE)HEG) 2 -K) 2 -K-Dpr-[ 18 F]FBOA showed excellent imaging of M21-melanomas in mice. In conclusion, the new two-step chemoselective 18 F-labeling fulfills all requirements for large scale syntheses of peptides in clinical routine. This methodology is also adaptable to other radioisotopes ( e.g. radiohalogenation in general) and will thus offer a broad field of application.

[ 11 C]Formic acid can be produced from no-carrier-added [ 11 C]carbon dioxide reliably and instantaneously in almost quantitative radiochemical yield using lithium triethylborohydride in THF. It can react, either on a solid support or as its non-hydrolysed LiEt 3 B-adduct, with a complex formed from hexachloroacetone and triphenylphosphine in THF at room temperature to give, again almost quantitatively, [ 11 C]formyl chloride. The latter decomposes instantaneously to give [ 11 C]carbon monoxide, providing an interesting alternative for current methods of [ 11 C]carbon monoxide production in radiopharmaceutical chemistry. [ 11 C]Formyl chloride has also potential in low-temperature N-formylation.

A procedure for the reliable production of the novel PET D2 receptor ligand (N-[ 11 C]methyl)benperidol ([ 11 C]NMB) is described. The method is based on N-methylation of benperidol using [ 11 C]methyl iodide from the PETtrace MeI MicroLab, with product purification via normal-phase HPLC. Batch yields of 2.5±0.9 GBq (68±25 mCi) of [ 11 C]NMB are routinely (n=16) obtained, with a radiochemical purity >98% and an average specific activity of over 40.7 TBq (1100 Ci)/mmol. The overall radiosynthesis, purification, and pre-release quality control testing is accomplished within 50 minutes. The procedure described herein produces a radiopharmaceutical product that is suitable for D2 receptor studies using PET or microPET imaging.

The synthesis of [ 11 C]DASB is known to be performed by reacting the demethyl-DASB precursor with [ 11 C]methyl iodide but the necessary reaction parameters had hitherto not been determined. In this work the dependence of the labelling yield on reaction temperature, reaction time, precursor concentration and type of solvent was investigated. Best results were found when methylation was carried out at 100 °C within 2 min using 4 mg/ml demethyl precursor in DMSO. With respect to [ 11 C]methyl iodide a radiochemical yield of 74%±3% [ 11 C]DASB was achieved. In addition, the synthesis was transferred to a remotely controlled module. A carbon-11 production for 1 h at 50 μA resulted in 3800-4300 MBq [ 11 C]DASB with a specific activity of 152-211 GBq/μmol (4.1-5.7 Ci/μmol) (EOS) and a radiochemical purity of >95% in a sterile solution ready for injection. The total synthesis time was 45 min after EOB.

In vivo labelling of serotonergic receptors (5HT) could be a useful tool for understanding the physiological and pathophysiological role of neurodegenerative disorders. 1-[2,5-Dimethoxy-4-iodophenyl]-2-aminopropane (DOI), a well known agonist with high affinity to 5HT 2 receptors, was labelled with C-11 for PET. Here we report the evaluation of the mono-methylated and dimethylated analogs of DOI for PET. The syntheses of [N- 11 C-methyl]-DOI ([ 11 C]MDOI) and [N- 11 C-dimethyl]-DOI ([ 11 C]DMDOI) were optimized resulting in radiochemical yields of up to 43%, allowing efficient production for clinical use. High affinities for the 5HT 2A and 5HT 2C receptors with a slight preference for 5HT 2A were found for MDOI, similar to the highly potent hallucinogen DOI.

The one-step radiosynthesis of 4-([ 18 F]fluoromethyl)-2-chlorophenylisothiocyanate 18 F-7 as a novel bifunctional 18 F-labelling agent is described. Optimised reaction conditions in a remotely controlled synthesis module gave isothiocyanate 18 F-7 in radiochemical yields of 45% (decay-corrected) within 40 min and high radiochemical purity of >95% after solid-phase-extraction. Coupling of compound 18 F-7 with the primary amine benzylamine as a model reaction afforded the corresponding ((4-[ 18 F]fluoromethyl)-2-chloro-phenyl)-benzyl thiourea 18 F-8 in a high radiochemical yield of >90%. Stability studies of thiourea 18 F-8 in terms of radiodefluorination showed appreciable buffer stability at pH 7.4, whereas significant radiodefluorination was observed when 18 F-8 was incubated in buffers at pH 3.6 and pH 9.4. Preliminary dynamic PET studies with thiourea 18 F-8 in male Wistar rats showed high bone accumulation, indicative of high in vivo radiodefluorination.

Rare earth elements (REE), a group of elements with atomic numbers from 57 to 71, have been widely applied in recent years not only in industry but also in agriculture, forestry, animal husbandry and medicine. Numerous anthropogenic activities make REE to easily enter the environment and finally the human body via the food chain. Therefore, detailed studies on chemical behavior of these metals in environmental and biological systems are imperative. Isotopic tracer method is especially suited to such studies and has played an important role in assessing the environmental effects of REE. In this paper, some recent progress in the study of chemical behavior of REE in environmental and biological sciences made by the isotopic tracer method is outlined.

A new method of radiolabelling of humic substances (HS) in the aqueous phase has been developed. Radiolabelling with the short-lived positron-emitter 18 F was carried out via diazonium coupling to electron-rich aromatic residues of the humic substances. Labelling yields of up to 75% were obtained after optimization of the synthetic procedure. Introductory experimental steps were performed for testing the labelling stability of the humic substances with ultrafiltration, electrophoretic and chromatographic methods.

Instrumental neutron activation analysis has been used for the analysis of seven varieties of medicinal herbs generally used by the people of South Asian region. Twenty-one trace elements (essential, toxic and non-essential) were determined. This data should not only be helpful in establishing the base-line values in these medicinal herbs but also in correlating their role as therapeutic agents. A comparison of our data with literature values shows variation in trace element contents of same species of different origin which can be attributed to ecological and geographical variations to some extent; however an exact interpretation demands further extensive investigations.

Extensive work is under way using High Resolution-ICP-MS for 90 Sr, 234 U, 235 U, 238 U, 239 Pu, 240 Pu, and 241 Am detection. Sample preparation procedures based on liquid-liquid extraction and ion exchange chromatography were developed. Sr, U, Pu, and Am were separated from their matrix and concentrated to improve the power of detection in the mass spectrometer. A microconcentric nebulizer with a desolvation introduction system (Ardius) is used. Instrumental limits of detection using Sr and U standard solutions are 0.01 ppt and 0.006 ppt for Sr and U, respectively. A study is presented on the mass interferences for the specified radionuclides. In the environmental samples investigated the 90 Sr/ 86 Sr isotope ratio is 6.02×10 -9 and for 240 Pu/ 239 Pu the isotope ratio is 0.17.

The ionizing radiation dose from building materials containing fly ash (FA) has been studied. Ceramic products, plates, bricks and blocks containing fly ash have been studied and compared to other construction materials for both natural radionuclides content (NORM), radon exhalation rate and gamma radiation dose .The total radiation dose due to walls built from ceramic blocks containing FA (45% fly ash), was found to be lower than radiation doses due to walls of other construction materials, Assuming two walls (the exterior ones) built of this ceramic material the doses are 0.09-0.13 mSv/y for ceramic materials densities of 800 and 1200 kg/m 3 , respectively.