Authors:M. Kohlíčková-Koudelková, R. Konířová, and V. Jedináková-Křížová
A large group of radiopharmaceuticals includes complex radionuclide-ligand compounds which are very sensitive to the preparation conditions, as for example pH of reaction mixture, incubation time, temperature, molar ratio of reagents, etc. It is necessary to find the optimum condition for the formation of the radionuclide-ligand complex and to select the convenient analytical methods to determine the purity of the product. The preparation of radiopharmaceuticals labeled by rhenium-186 or rhenium-188 requires the addition of a reducing agent (commonly stannous chloride) to the reaction mixture in order to reduce perrhenate to a lower oxidation state which is capable of complex formation. For rhenium concentration up to approximately 10-5 mol/l, the molar excess of reduction agent over perrhenate is usually higher than 800 to reach the optimum yield of reduction and complexation (between 80-95%). Because of the potentially toxic effect of SnCl2 the reduction of perrhenate by stannous chloride was studied in detail to find the way for decreasing the concentration of reducing agent in the reaction mixture without significant lowering of the yield of perrhenate reduction. The reduction of perrhenate was determined by electromigration methods, i.e., capillary electrophoresis (CZE) and isotachophoresis (ITP), and thin-layer chromatography (TLC) with radiometric detection. The highest degree of reduction of perrhenate was obtained at pH 2 at perrhenate concentration ranging from 10-4 to 10-3 mol/l. The stability of reduced rhenium against a pH change from 2 to 5.5 (which corresponds to the pH close to physiological values) was tested as well. The influence of the presence of ascorbic acid as an antioxidant in the reaction mixture on the stability of the preparation against the pH change was determined. The stability of reduced rhenium against dilution of rhenium in the reaction mixture to the concentration suitable for the application in radiotherapy was also found out. The data acquired by capillary electrophoresis, isotachophoresis and thin-layer chromatography are comparable. Results obtained in these experiments were applied for the study of rhenium complexes with hydroxyethylidenediphosphonic acid (HEDP).
Authors:F. Macášek, P. Kováč, P. Rajec, and R. Lepej
Except the nuclear fuel reprocessing and nuclear materials safeguards, at present there are two areas of an increased responsibility
of nuclear scientists for their results: radioecology and human medicaments. At both of them, quality and trustfulness of
results is of great importance for their end-users and may have serious economical and legal consequences. The trends of implementation
of good laboratory and manufacturing practices under umbrella of international quality management standards like ISO 17025:2005
and ISO 9001:2000 in radiochemical and radiopharmaceutical laboratories are discussed as expanding to “good scientific practice”.
The case studies of the Comenius University laboratory LARCHA authorized for radiochemical analysis, and the company BIONT
producing medical radionuclides and PET radiopharmaceuticals are used as the examples.
105Rh[1,5,9,13-tetrathiacyclohexadecane-3,11-diol] is a promising drug precursor for targeted radiotherapy. Nevertheless, the
axial position of chloride ions in the complex structure and their weak binding to rhodium centre, due to HSAB concept, make
such a complex subject to modifying action of certain sulphuric ligands, like human plasma thiol antioxidants: glutathione
and cysteine. Experiments were performed with both radioactive 105Rh and inactive rhodium. The complexation of rhodium with 1,5,9,13-tetrathiacyclohexadecane-3,11-diol (16S4diol) resulted in three distinct peaks seen on UV, radiometric and MS chromatograms. The substitution of chlorides was noted
in over 80% of 105[Rh(16S4diol)Cl2]+ units after incubation with glutathione, and less than 10% of complex units after incubation with cysteine (24 h, 37 °C).
Reaction of 105[Rh(16S4diol)Cl2]+ with 1,8-octandithiol and 1,9-nonandithiol resulted in disappearance of the complex peak and occurrence of two new peaks.
Product of RhCl3 and 16S4diol reaction is a mixture of three distinct forms having different number of chlorine atoms. Our in vitro experiments suggest
that the substitution of axial chlorides with glutathione and cysteine might also occur in vivo in human plasma. Glutathione
shows higher reactivity than cysteine in replacement reaction. Axial positions in precursor might be effectively blocked by
1,8-octandithiol and 1,9-nonandithiol.
Authors:Erik de Blois, Ho Chan, Kamalika Roy, Eric Krenning, and Wouter Breeman
PET with 68Ga from the TiO2- or SnO2- based 68Ge/68Ga generators is of increasing interest for PET imaging in nuclear medicine. In general, radionuclidic purity (68Ge vs. 68Ga activity) of the eluate of these generators varies between 0.01 and 0.001%. Liquid waste containing low amounts of 68Ge activity is produced by eluting the 68Ge/68Ga generators and residues from PET chemistry. Since clearance level of 68Ge activity in waste may not exceed 10 Bq/g, as stated by European Directive 96/29/EURATOM, our purpose was to reduce 68Ge activity in solution from >10 kBq/g to <10 Bq/g; which implies the solution can be discarded as regular waste. Most efficient
method to reduce the 68Ge activity is by sorption of TiO2 or Fe2O3 and subsequent centrifugation. The required 10 Bq per mL level of 68Ge activity in waste was reached by Fe2O3 logarithmically, whereas with TiO2 asymptotically. The procedure with Fe2O3 eliminates ≥90% of the 68Ge activity per treatment. Eventually, to simplify the processing a recirculation system was used to investigate 68Ge activity sorption on TiO2, Fe2O3 or Zeolite. Zeolite was introduced for its high sorption at low pH, therefore 68Ge activity containing waste could directly be used without further interventions. 68Ge activity containing liquid waste at different HCl concentrations (0.05–1.0 M HCl), was recirculated at 1 mL/min. With Zeolite
in the recirculation system, 68Ge activity showed highest sorption.
Authors:C. Dirks, B. Scholten, S. Happel, A. Zulauf, A. Bombard, and H. Jungclas
Cu isotopes (e.g. 64Cu) increasingly find use in radiopharmaceutical applications, accordingly fast and reliable methods for the production of
these isotopes are needed. The aim of the presented project is the characterization of a Cu selective extraction chromatographic
resin for the fast and selective separation of Cu radionuclides, e.g. from irradiated targets. The characterisation of the
resin includes the determination of weight distribution factors Dw of Cu, Ni, Zn and other potentially interfering elements and impurities for varying acids and pH values, the influence of
macro amounts of Ni and Zn on the extraction of Cu as well as the influence of other potential interferents. Based on the
obtained results, a method for the separation of Cu and its purification from irradiated Ni or Zn targets was developed and
tested on simulated Ni and Zn targets.
The biologic profiles of a hepatobiliary radiodiagnostic agent,99mTc-N/p-butylphenylcarbamoylmethyl/iminodiacetic acid,99mTc-p-butyl HIDA for short, are described in terms of its pharmacokinetics in normal rats over a 24 h period. It could be used to monitor the quality of this hepatobiliary radiopharmaceutical if prepared in an in-house hospital radiopharmacy.
Authors:Rubel Chakravarty, Meera Venkatesh, and Ashutosh Dash
A novel electrochemical process to avail clinical grade 99mTc from (n,γ)99Mo has been demonstrated. The electrochemical parameters were optimized to maximize the 99mTc yield with minimal 99Mo contamination. 99Mo/99mTc generators containing up to 29.6 GBq (800 mCi) 99Mo were developed and their performance were extensively evaluated for 10 days without changing the operating conditions.
Very high radioactive concentration of 99mTcO4− of acceptable quality, commensurate with hospital radiopharmacy requirements could be availed from the system with >90% yield.
The compatibility of the product for the formulation of 99mTc labeled radiopharmaceuticals such as 99mTc-DMSA and 99mTc-EC was found to be satisfactory in terms of high labeling yields. The proposed route represents an important step for enhancing
the scope of accessing clinical grade 99mTc from low specific activity (n, γ)99Mo.
Authors:Roman Staník, Jan Světlík, and Ivan Benkovský
Meso-2,3-dimercaptosuccinic acid (DMSA) forms stable complexes with a remarkable wide range of metal ions. This relatively small
molecule has attracted increasing attention in the field of radiopharmacy, treatment of heavy metal intoxications and nanoparticles
preparation. In this review detailed summary of all physical, chemical and biological properties of DMSA and its complex compounds
with 99mTc, 186/188Re, 166Ho, 177Lu and 90Y is provided. The clinical utilisation of DMSA complexes in the nuclear medicine and its use for treatment of heavy metal
intoxication is briefly summarised. The aspects of its application in the field of nanoparticles preparation is behind the
scope of this review, therefore it is only shortly described.