Johan Rajander

Environmental monitoring of trace elements in bark of Scots pine by thick-target PIXE

Bark samples were taken from Scots pines (Pinus sylvestris L.) from a polluted area near a metal plant and from a relatively non-polluted site. Thick-target particle-induced X-ray emission (PIXE) was used for the analyses after different types of prepreparation of the samples. The bark samples were analysed directly by radially scanning from inner to outer bark in order to study the variability of elemental concentrations in different layers. Some clear differences were found in the chemical composition of the inner and outer bark. The lowest detection limits for the analyses of heavy metal ions were obtained by combining dry ashing at 550 °C with the PIXE method. More than 100 times higher concentrations were found for the heavy metal ions Fe, Ni, Cu, Zn, Ga, As and Pb in the bark samples from a polluted area in comparison to samples from a non-polluted area. The work demonstrated that external-beam thick-target PIXE is a sensitive and reliable method for quantitative determination of heavy metals in tree bark samples.

64Cu- and 68Ga-labelled [Nle(14),Lys(40)(Ahx-NODAGA)NH2]-exendin-4 for pancreatic beta cell imaging in rats.

PURPOSE Glucagon-like peptide-1 receptor (GLP-1R) is a molecular target for imaging of pancreatic beta cells. We compared the ability of [Nle(14),Lys(40)(Ahx-NODAGA-(64)Cu)NH2]-exendin-4 ([(64)Cu]NODAGA-exendin-4) and [Nle(14),Lys(40)(Ahx-NODAGA-(68)Ga)NH2]-exendin-4 ([(68)Ga]NODAGA-exendin-4) to detect native pancreatic islets in rodents. PROCEDURES The stability, lipophilicity and affinity of the radiotracers to the GLP-1R were determined in vitro. The biodistribution of the tracers was assessed using autoradiography, ex vivo biodistribution and PET imaging. Estimates for human radiation dosimetry were calculated. RESULTS We found GLP-1R-specific labelling of pancreatic islets. However, the pancreas could not be visualised in PET images. The highest uptake of the tracers was observed in the kidneys. Effective dose estimates for [(64)Cu]NODAGA-exendin-4 and [(68)Ga]NODAGA-exendin-4 were 0.144 and 0.012 mSv/MBq, respectively. CONCLUSION [(64)Cu]NODAGA-exendin-4 might be more effective for labelling islets than [(68)Ga]NODAGA-exendin-4. This is probably due to the lower specific radioactivity of [(68)Ga]NODAGA-exendin-4 compared to [(64)Cu]NODAGA-exendin-4. The radiation dose in the kidneys may limit the use of [(64)Cu]NODAGA-exendin-4 as a clinical tracer.

Synthesis and preclinical characterization of [64Cu]NODAGA-MAL-exendin-4 with a Nε-maleoyl-l-lysyl-glycine linkage

INTRODUCTION Renal localization of high radioactivity levels during targeted imaging compromises tissue visualization in the kidney region and limits diagnostic accuracy. Radioiodinated antibody fragments with a renal enzyme-cleavable N(ε)-maleoyl-L-lysyl-glycine (MAL) linkage demonstrated low renal radioactivity levels in mice, from early postinjection times. This study tested the hypothesis whether a (64)Cu-labeled NODAGA-exendin-4 peptide with a MAL linkage ([(64)Cu]NODAGA-MAL-exendin-4) could decrease kidney radioactivity levels in rats, compared to a [(64)Cu]NODAGA-exendin-4 reference, without impairing the radioactivity levels in the target tissue. METHODS NODAGA-MAL-exendin-4 was synthesized in a two-phase approach using solid support to prepare maleoyl-derivatized NODAGA followed by Michael addition to cysteine-derivatized exendin-4 in solution. Radiolabeling was performed in buffered aqua with [(64)Cu]CuCl2, which was produced via the (64)Ni(p,n)(64)Cu nuclear reaction. The in vitro and in vivo stability, lipophilicity, and distribution kinetics in major rat organs for [(64)Cu]NODAGA-MAL-exendin-4 were studied and compared to [(64)Cu]NODAGA-exendin-4. Labeling of pancreatic islets was assessed using autoradiography. RESULTS NODAGA-MAL-exendin-4 was synthesized, with an overall yield of 9%, and radiolabeled with (64)Cu with high specific radioactivity. Serum incubation studies showed high stability for [(64)Cu]NODAGA-MAL-exendin-4. Similar tissue distribution kinetics was observed for [(64)Cu]NODAGA-MAL-exendin-4 and [(64)Cu]NODAGA-exendin-4, with high kidney radioactivity levels. CONCLUSIONS The incorporated MAL linkage in [(64)Cu]NODAGA-MAL-exendin-4 was unable to reduce kidney radioactivity levels, compared to [(64)Cu]NODAGA-exendin-4. The applicability of metabolizable linkages in the design of kidney-saving exendin-4 analogs requires further investigation.

Isomerism of [64Cu-NOTA-Bn]-Labeled Radiotracers: Separation of Two Complex Isomers and Determination of Their Interconversion Energy Barrier Using Ion Pair Chromatography

The model complex [(64)Cu((S)-p-NH(2)-Bn-NOTA)](-) ([(64)Cu]1) was used to study the isomerism of [(64)Cu-NOTA-Bn]-labeled radiotracers. Two complex isomers [(64)Cu]1a and [(64)Cu]1b, which were formed at a ratio of 1:9 during the complexation of [(64)Cu]Cu(2+) with (S)-p-NH(2)-Bn-NOTA, were separated using ion pair chromatography. To study the interconversion, the nonradioactive complex isomers Cu1a and Cu1b were separated and thermally treated at 90 °C in both ammonium acetate solution and deionized water. A faster interconversion rate was observed for both isomers with lower concentrations of ammonium ions. At the end of reaction, the thermodynamic Cu1a to Cu1b equilibrium ratio was 6:94. The particular energy barriers of the interconversion for Cu1a and Cu1b were 130 kJ mol(-1) and 140 kJ mol(-1). Spectrophotometric measurements with Cu1a and Cu1b revealed two isomers adopting different geometrical configurations.

High specific activity 61Cu via 64Zn(p,α)61Cu reaction at low proton energies

The PET radionuclide (61)Cu is accessible through several nuclear reactions. Besides the common production route via (61)Ni(p,n)(61)Cu the (64)Zn(p,α)(61)Cu reaction offers some advantages. Especially the comparatively cheap enriched (64)Zn makes this process economical. For fast product purification and recycling of target material an ion exchange cascade was developed. In addition a separation technique with a copper selective resin was tested. (61)Cu with specific activities up to 1000 GBq/μmol was produced with these methods.

Automation of 64Cu production at Turku PET Centre

At Turku PET Centre automation for handling solid targets for the production of (64)Cu has been built. The system consists of a module for moving the target from the irradiation position into a lead transport shield and a robotic-arm assisted setup for moving the target within radiochemistry laboratory. The main motivation for designing automation arises from radiation hygiene.

Monitoring of chromium, copper and arsenic in contaminated soils using thick-target PIXE

Abstract Soil contamination by toxic metal ions is one of the most serious environmental problems today. In this work soil samples from an area where a wood preservation plant has been active were studied. Chromium, copper and arsenic (CCA) are the main metal ions used in preservation of lumber. For the monitoring of these metal ions and of other elements in soil, thick-target PIXE (TTPIXE) has been proved to be a successful method. About 20 elements were quantitatively determined in the soil samples from the contaminated area and from a reference area. The reliability of the results was evaluated by analysing geochemical certified reference materials (CRMs) of chemical compositions similar to the soil samples.

Thick-Target PIXE Analysis of Trace Elements in Wood Incoming to a Pulp Mill

Summary Trunk-wood samples of wood raw material incoming to a pulp mill were analysed by thick-target particle induced X-ray emission (PIXE). The tree species studied were pine and spruce from Finland, birch from Finland and Poland and eucalyptus from Uruguay. The wood samples were dry ashed to 550 °C prior to the analysis in order to increase the sensitivity of the method. The method was calibrated and validated using some wood based certified reference materials. The elements determined with the method were P, S, K, Ca, Ti, Mn, Fe, Ni, Cu, Zn, Pb, Sr, Rb, Ba and F. The concentrations of the main elements P, S, K, Ca and Mn exceeded 50 ppm in most wood samples. The concentrations of heavy metal ions like Cu, Ni and Pb in the samples studied were below or close to 1 ppm. The ash content of birch, pine and spruce wood were in the range 0.2–0.4% and that of eucalyptus ca 0.5%.

Thick-target PIXE analysis of chromium, copper and arsenic impregnated lumber

Chromium, copper and arsenic (CCA) have for decades been used for wood preservation. Of these elements especially arsenic is very toxic. As CCA impregnated wood is still today used for many construction purposes, a monitoring of these metal ions is of great environmental importance. Thick-target PIXE is a powerful method for the determination of trace metals in wood. The TTPIXE method enabled study of variations of the elemental concentrations in lumber treated with CCA impregnation solution. Distribution patterns were obtained for both naturally occurring elements and elements introduced in the treatment process. During the impregnation process a desorption of e.g. alkali metal ions takes place from the wood. The sensitivity of the method is improved by dry ashing of the samples prior to PIXE analysis. The TTPIXE method was calibrated and validated using international certified reference materials (CRM) based on wood material. ” 1999 Published by Elsevier Science B.V. All rights reserved.

Solid-Supported Porphyrins Useful for the Synthesis of Conjugates with Oligomeric Biomolecules.

meso-Tris(pyridin-4-yl)(4-carboxyphenyl)porphyrin and 2-(1-hexyloxyethyl)-2-devinyl pyropheophorbide-a (Photochlor, HPPH) were amide-coupled to 1R,2S,3R,4R-2,3-dihydroxy-4-(hydromethyl)-1-aminocyclopentane and immobilized via an ester linkage to long chain alkyl amine-derivatized controlled pore glass (LCAA-CPG). The applicability of these supports (5 and 6) for the synthesis of porphyrin conjugates with oligomeric biomolecules was demonstrated using an automated phosphoramidite coupling chemistry. Cleavage from the support with concentrated ammonia gave the products, viz., porphyrin conjugates of oligonucleotides (7-9) and dendritic glycoclusters (10-13) and a cyclooctyne derivative (14) in 23-58% yield. In addition, the synthesized cyclooctyne derivative of meso-tris(pyridin-4-yl)(4-carboxyphenyl)porphyrin (14) was conjugated with an azidopropyl-modified hyaluronic acid (19). The hyaluronic acid-porphyrin conjugate (15) was radiolabeled with (64)Cu and its (15[(64)Cu]) receptor binding affinity to CD44-expressing tumor cells was evaluated.