Volume 103, Issue 11

The concentrations of the long-lived nuclear reaction products 129 I and 36 Cl have been measured in samples from the MEGAPIE liquid metal spallation target. Samples from the bulk target material (lead-bismuth eutectic, LBE), from the interface of the metal free surface with the cover gas, from LBE/steel interfaces and from noble metal absorber foils installed in the cover gas system were analysed using Accelerator Mass Spectrometry at the Laboratory of Ion beam Physics at ETH Zürich. The major part of 129 I and 36 Cl was found accumulated on the interfaces, particularly at the interface of LBE and the steel walls of the target container, while bulk LBE samples contain only a minor fraction of these nuclides. Both nuclides were also detected on the absorber foils to a certain extent (≪ 1% of the total amount). The latter number is negligible concerning the radio-hazard of the irradiated target material; however it indicates a certain affinity of the absorber foils for halogens, thus proving the principle of using noble metal foils for catching these volatile radionuclides. The total amounts of 129 I and 36 Cl in the target were estimated from the analytical data by averaging within the different groups of samples and summing up these averages over the total target. This estimation could account for about half of the amount of 129 I and 36 Cl predicted to be produced using nuclear physics modelling codes for both nuclides. The significance of the results and the associated uncertainties are discussed.

The production of non-commercially available 135 La by proton irradiation of an isotopically enriched [ 135 Ba]BaCO 3 target at a cyclotron is described. The purification of the radionuclide was performed by a La-selective resin. 135 La was separated in no-carrier-added (n.c.a) form in a nitric acid solution with a radiochemical yield of 83 ± 5% and a total activity per batch of 43 ± 3 MBq. The enriched [ 135 Ba]Ba was recycled to the carbonate form with a recovery of 90 ± 3%. On the basis of a detection limit of 1 Bq/mL, solutions of n.c.a. 135 La could be measured down to the 10 – 15  mol/L concentration range.

The oestrogen receptor (ER) is an important tumour target for molecular imaging and radionuclide therapy due to its overexpression in many malignant cells as compared to normal cells. Aiming to find new functional molecular imaging/therapeutic agents for ER positive tumours, we have synthesized a new estradiol derivative substituted at the 16- α position with a diethylene triamine tetraacetic acid (DTTA)-like chelating ligand through a four-carbon spacer. The new bioconjugate (H 4 L), was used to synthesize the corresponding indium complexes (InL/[ 111 In]L). The radioactive complex [ 111 In]L was prepared in high yield (>98%) at final concentrations of 1 · 10 – 4  M and its chemical identity was ascertained by comparing its HPLC gamma-chromatogram to the HPLC UV-vis-chromatogram of the InL analogue. [ 111 In]L is hydrophilic and kinetically stable in the presence of an excess of apo-transferrin and in human blood serum. Cellular studies in breast cancer cells (MCF-7 and MDA-MB-431) suggest that [ 111 In]L uptake may be mediated by an ER dependent mechanism. Biodistribution studies were performed in mice indicating a rapid clearance from most organs and a slow total excretion that occurs mainly by hepatobiliar pathway. High in vivo stability of [ 111 In]L was confirmed by HPLC analysis of urine and blood samples. Nevertheless, the hydrophilicity, the low ER affinity and the biodistribution of [ 111 In]L indicate that structural modifications are required to improve its behaviour for ER targeting in vivo .

Cladribine, a purine analogue antimetabolite, was radioiodinated with 125 I via direct electrophilic substitution reaction. The maximum radiochemical yield (92.5 ± 0.8%) was obtained when the reaction was done at ambient temperature for 30 min using 100 μg of Cladribine and 10 μg N-chlorosuccinamide (NCS) in 150 μL of 0.2 M phosphate buffer, pH 7. In vitro stability studies of HPLC purified 125 I-Cladribine sample dissolved in 0.5 ml of 0.2 M phosphate buffer pH 7 at ambient temperature showed that 125 I-Cladribine is stable up to 12 h post labeling. Biodistribution results revealed excretion of 125 I-Cladribine mainly by kidneys. The uptake of 125 I-Cladribine in the induced Ehrlich Ascites Carcinoma was 2.8 ± 0.4 %ID/g at 1 h post injection with maximum tumor/muscle ratio of 5.5. The good uptake of 125 I-Cladribine confirms the molecular docking studies results which indicate that iodinated Cladribine binds with polymerase enzyme with a good –CDOCKER energy. As a result, radioiodinated Cladribine may be used as a valuable agent for tumor diagnosis and therapy.

In this study, production, quality control and biodistribution studies of 166 Ho-alendronate have been presented and followed by dosimetric evaluation for human based on biodistribution data in wild-type rats. 166 Ho chloride was obtained by thermal neutron irradiation of natural 165 Ho(NO 3 ) 3 samples. 166 Ho-alendronate complex was prepared by adding the desired amount of alkaline alendronate solution (0.2 mL, 150 mg/mL) to 3–5 mCi of the 166 HoCl 3 solution. Radiochemical purity of the complex was monitored by instant thin layer chromatography (ITLC). 166 Ho-alendronate complex was prepared in high radiochemical purity (> 99%, ITLC) and specific activity of 4.4 GBq/mmol. Stability studies of the complex in the final preparation and in the presence of human serum were performed up to 48 h. The major accumulation of the radio-complex was in the bone tissues followed by absorbed dose evaluation of each human organ by RADAR software used for modelling the radiation dose delivered. The final preparation was administered to wild-type rats and biodistribution of the complex was performed 2–48 h post injection showing major accumulation of the complex in the bone tissue. The highest absorbed dose for 166 Ho-alendronate is observed in bone surface and red marrow with 2.670 and 1.880 mSv/MBq; respectively. These findings suggest that 166 Ho-alendronate has considerable characteristics compared to 166 Ho-DOTMP and can be a possible candidate for bone marrow ablation in patients with multiple myeloma.

Boron neutron capture therapy (BNCT) employs 10 B-pharmaceuticals administered for the treatment of malignancies, and subsequently irradiated with thermal neutrons. So far, clinical established pharmaceuticals like boron phenylalanine (BPA) or sodium boron mercaptate (BSH) use imperfect (BPA) or passive (BSH) targeting for accumulation at target sites. Due to the need of a selective transportation of boron drugs into cancer cells and sparing healthy tissues, we combined the BNCT approach with the specific and effective folate receptor (FR) targeting concept. The FR is overexpressed on many human carcinomas and provides a selective and specific target for molecular imaging as well as for tumor therapy. We synthesized and characterized a carborane-folate as well as a BSH-folate to study their in vitro characteristics and their potential as new boron-carriers for BNCT. Uptake studies were carried out using human KB cells showing a significant increase of the boron content in cells and demonstrating the successful combination of active FR-targeting and BNCT.

Livers, kidneys and muscles of large herbivorous animals: roe deer, red deer and fallow deer, collected in Northern Poland, were the subject of the investigation. The concentration of 241 Pu ranged widely between 1.31 ± 0.28 and 214.5 ± 25.8 mBq kg – 1  ww and decreased in the order kidney > liver > muscle. The average values of the activity concentrations of 241 Pu were 11.5 ± 1.8 mBq kg – 1  ww in muscles, 14.0 ± 2.25 mBq kg – 1  ww in liver and 85.5 ± 9.7 mBq kg – 1  ww in kidneys. As statistically checked the sampling location, sex, age and species of animals did not influence on plutonium concentrations of the analyzed samples. Only the organ type significantly influenced 241 Pu content. The values of 241 Pu/ 29+240 Pu activity ratio in analyzed samples ranged from 7.12 ± 2.15 to 99.3 ± 16.4 and the results showed the main source of plutonium in analyzed organs could be the Chernobyl accident.