Primary standardization and determination of gamma ray emission intensities of Ho-166.

The procedure followed by the Nuclear Metrology Laboratory (LMN) at the IPEN-CNEN/SP, in São Paulo, for the primary standardization of 166Ho is described. The activity of 166Ho was determined by the efficiency extrapolation technique applied to a 4πß(PC)-γ coincidence system using a gas flow proportional counter in 4π geometry coupled to a 76 × 76 mm NaI(Tl) crystal. The results for the γ-rays intensities at 80.57 and 1379.45 keV were 0.0651(11) and 0.00904(11), respectively.

Improvement of the WBC calibration of the Internal Dosimetry Laboratory of the CDTN/CNEN using the physical phantom BOMAB and MCNPX code.

The Laboratory of Internal Dosimetry of the Center for Development of Nuclear Technology (LDI/CDTN) is responsible for routine internal monitoring of occupationally exposed individuals. The determination of photon emitting radionuclides in the human body requires calibration of the detector in specific counting geometries. The calibration process uses physical phantoms containing certified activities of the radionuclides of interest. The objective of this work was to obtain calibration efficiency curves of the Whole Body Counter in operation at the LDI/CDTN using a BOMAB physical phantom and Monte Carlo simulations.

Fatores de correção volumétrica na medição de atividade de 99mTc e 123I em calibradores de radionuclídeos / Volume corrections factors in the measurement of 99mTc and 123I activities in radionuclide calibrators

OBJETIVO: Determinar os fatores de correção para a variação volumétrica dos radiofármacos contidos em recipientes de diferentes geometrias. Comparar a influência desses fatores na determinação da atividade de 99mTc e 123I utilizando dois tipos de calibradores: um com câmara de ionização e outro com detector Geiger-Müller (G-M). Avaliar o desempenho de calibradores de alguns serviços de medicina nuclear em medição de atividade de 99mTc e 123I. MATERIAIS E MÉTODOS: Foram utilizados oito calibradores, frascos de vidro 10R, seringas de plástico de 3 e 5 mL e soluções de 99mTc e 123I. Os fatores de correção foram determinados a partir das medições práticas da variação da leitura do calibrador com a variação do volume da solução no recipiente. O desempenho foi avaliado em relação ao critério de aceitação de ±10% de exatidão exigida pela norma brasileira. RESULTADOS: A variação da resposta do calibrador com a variação do volume do frasco foi bem maior no calibrador que utiliza G-M. Ela também foi maior para 123I do que para 99mTc. CONCLUSÃO: Os resultados confirmam que a resposta dos calibradores depende do volume contido nos recipientes. Essa dependência é mais crítica para os calibradores equipados com detector G-M e para 123I quando comparado com 99mTc.

OBJECTIVE: To determine correction factors for the variation in volume of radiopharmaceuticals in containers of different geometries, comparing the influence of such factors on the determination of 99mTc and 123I activity with two types of calibrators - one with ionization chamber and another with Geiger-Müller (G-M) detector -; and to evaluate calibrators performance in the measurement of 99mTc and 123I activities. MATERIALS AND METHODS: Eight calibrators, 10R glass vials, 3 and 5 mL plastic syringes and 99mTc and 123I solutions were utilized. The correction factors were determined with basis on practical measurements of the variation in the calibrators' response according to the volume of radionuclide solution in the glass vials. The performance was evaluated according to the acceptance criterion of ±10% accuracy required by the Brazilian standard. RESULTS: The variation of the calibrators' response according to the variation in radionuclide volume was reasonably greater in the calibrator with G-M detector. It was also greater for 123I than for 99mTc. CONCLUSION: The results confirm that the calibrators' response depends on the radionuclide volume contained in the vials. Such dependence is more critical for the calibrators equipped with G-M detector and for 123I as compared with 99mTc.

Standardization of 65Zn by sum-peak method.

A commercial solution of (65)Zn was standardized by the sum peak-method using a planar HPGe detector. The activity results were compared with measurements made with a well type 4πγ ionization chamber, which is traceable to BIPM.RI (II)-K2.Zn-65 key-comparison performed in 2002. The sum-peak value was 42.79 kBq/g and the ionization chamber value was 42.74 kBq/g both at the reference date. The uncertainty obtained in the sum peak standardization was 0.25% (k=1), and in the ionization chamber was 0.85% (k=1). The results showed that sum-peak method can be used in (65)Zn standardization and this method is easier, simpler and more practical than others methods.

Radioactivity measurements of 177Lu, 111In and 123I by different absolute methods.

The activities of (177)Lu, (111)In and (123)I solutions have been absolutely determined using three different measurement methods. (177)Lu solution was standardized using the 4πß(PC)-γ(NaI) coincidence and 4πß(LS)-γ(NaI) live-timed anticoincidence methods. For the (111)In and (123)I solutions, besides these two mentioned methods, the coincidence sum-peak method was also applied. The measured activities results using these different methods are consistent within the evaluated experimental uncertainties demonstrating the equivalence of these methods. As an additional contribution to nuclear data, the half-lives have been determined using a well type IG12 ionization chamber.

Evaluation of the planar sources surface homogeneity used to instruments calibration.

The surface homogeneity of planar sources used to calibrate contamination detectors is important considering that their dimensions are bigger than the most kind of detectors tested and the positioning in relation to the source may vary in each measurement. Using a special pancake detector the counting efficiency of alpha and beta sources was measured in several positioning covering all area of the sources. The (14)C source showed the worse performance and the (241)Am source showed the best behavior.

Determination of radionuclides in environmental test items at CPHR: traceability and uncertainty calculation.

Information about how the laboratory of Centro de Protección e Higiene de las Radiaciones (CPHR), Cuba establishes its traceability to the International System of Units for the measurement of radionuclides in environmental test items is presented. A comparison among different methodologies of uncertainty calculation, including an analysis of the feasibility of using the Kragten-spreadsheet approach, is shown. In the specific case of the gamma spectrometric assay, the influence of each parameter, and the identification of the major contributor, in the relative difference between the methods of uncertainty calculation (Kragten and partial derivative) is described. The reliability of the uncertainty calculation results reported by the commercial software Gamma 2000 from Silena is analyzed.

Radionuclide calibrator comparisons and quality improvement in nuclear medicine.

The traceability of activity measurements performed during the development phase of the radiopharmaceutical and in its clinical application is essential for establishing the comparability of clinical results reported in the nuclear medicine field. This paper presents and discusses the evaluation over time of the quality of activity measurement results obtained in Cuban nuclear medicine, on the basis of statistical samples taken during the radionuclide calibrator comparison program. An attempt is also made to evaluate the role played by such comparisons in quality measurement improvement in nuclear medicine, on the basis of results obtained in a number of countries and published by several authors over a period of time. Specifically, improvements of the measurement performance over time assessed by such exercises were found dissimilar in magnitudes for different countries. Two phases could be distinguished in the improvement process over time. Firstly, a fast improvement can be obtained resulting from the improvement in measurement accuracy of devices. After that, the achievement of new and sustained improvements goes slowly and requires an application of quality assurance programs where the qualification upgrading of personnel become an essential point.

Implementation of the TDCR liquid scintillation method at CNEA-LMR, Argentina.

During the last two years, a triple-to-double coincidence ratio (TDCR) system was assembled and adjusted at the CNEA-LMR, Argentina. The new counting system will add complementary capabilities to the absolute measurements section of the CNEA-LMR. This work describes its implementation and validation. Several checks and a set of beta-emitting standard solutions were used in order to perform the validation experiments. In preliminary measurements, a 3H LNHB solution with reference activity concentration of (119.7+/-0.9) kBq/g on 11 November 2003 was used. The CNEA-LMR TDCR counter gave, at the same reference date, an activity concentration of (120+/-1) kBq/g. Results and improvements are presented in detail. Concerning the asymmetry of the system, the quantum efficiency of the three photomultiplier tubes was studied for different operating conditions of the focusing voltage. The counter also includes an automatic system to change the efficiency by defocusing the photomultipliers and on the other hand, it was coupled to a HPGe detector to also measure beta-gamma coincidences.

The influence of uncertainties of measurements in laboratory performance evaluation using an intercomparison program of radionuclide assays in environmental samples.

To show the influence of measurement uncertainties in performance evaluation of laboratories, data from 42 comparison runs were evaluated using two statistical criteria. The normalized standard deviation, D, used by US EPA, that mainly takes into account the accuracy, and the normalized deviation, E, that includes the individual laboratory uncertainty used for performance evaluation in the key-comparisons by BIPM. The results show that data evaluated by the different criteria give a significant deviation of laboratory performance in each radionuclide assay when we analyse a large quantity of data.

Standardization and decay data determinations of 125I, 54Mn and 203Hg.

The absolute 4pi-betagamma coincidence counting has been used to measure the activity concentrations of 54Mn and 203Hg, and the Sum-Peak method was used for 125I. 54Mn and 125I radionuclides have been part of international key-comparisons coordinated by the Bureau International des Poids et Measures (BIPM) in 2003/2004, while 203Hg is part of the traceability programme of the National Laboratory for Ionizing Radiation Metrology (LNMRI)/Brazil. Three different detectors were used for the Sum-Peak method: 3''x3'' NaI(Tl) and 5''x5'' well NaI(Tl) scintillation detectors and a planar germanium detector. Direct measurements were made of the photon emission probabilities of the 35.5-, 834.8- and 279.2-keV gamma-rays of 125I, 54Mn and 203Hg to give values of (0.0667+/-0.0014), (0.9997+/-0.0055) and (0.8161+/-0.0005), respectively. The half-lives of 203Hg and 54Mn were also determined by means of a 4pigamma ionization chamber (203Hg) and by the reference source method using a HPGe detector (54Mn) to give values of (46.639+/-0.023) days and (312.1+/-0.9) days, respectively.

Implementation of a national metrology network of radionuclides used in nuclear medicine.

The Nuclear Medicine Services (NMS) in Brazil routinely use dose calibrators to measure the activity of solutions containing radiopharmaceuticals. These solutions are administered to patients with the intention to diagnose or treat illnesses. However, for optimal results, the activity of these radiopharmaceuticals must be determined as accurately as possible. The National Laboratory for Ionizing Radiation Metrology (LNMRI) led, since 1998, a comparison program for activity measurements of radiopharmaceuticals administered to patients in the NMS with the purpose promoting quality control. This program has been carried out successfully in Rio de Janeiro, but there is a need to implement it around the country. This can be resolved through the implementation of a network of regional laboratories at various locations throughout the national territory. Currently, such a network is active at a second site, located in Brasília, covering the needs of the Center-West Region, and at a third site, located in Porto Alegre, in the South Region. This work presents the results of comparisons for the radiopharmaceuticals nuclides 131I and 99Tcm and proves that the implementation of a radionuclide metrology network is feasible and viable.

Developing 152Eu into a standard for detector efficiency calibration.

A gamma-gamma coincidence experiment was performed to check the 152Eu 13-year decay scheme and the placement of the observed gamma-ray transitions. The multi-detector array for residual activity measurement of the Linear Accelerator Laboratory was used. The source activity was 1 MBq, and about 10(9) coincidence events were observed. About 30 gamma's were placed in the decay scheme and four 152Sm levels were added to the previously known set of levels fed in 152Eu 13-year decay.

Comparisons of activity measurements with radionuclide calibrators.

The correct administration to a patient of the prescribed activity of a radiopharmaceutical is an important factor to ensure the confidence in the diagnosis or the therapeutic efficiency, while at the same time keeping the unnecessary human exposure as low as possible. Comparisons of activity measurements for 131I, 201Tl and 99mTc with radionuclide calibrators were organized the first time in Cuba during 2002 with the aim of obtaining information about the quality of administration of radiopharmaceuticals. Ten Cuban nuclear medicine departments and the laboratories involved in the production of these kinds of compounds participated in the comparison runs. The results presented in this paper facilitated the identification of several problems and initiated corrective actions. In addition, they indicate the necessity of establishing Quality Systems in nuclear medicine in Cuba.

Intravascular brachytherapy to prevent restenosis: dosimetric considerations.

Acute myocardial infarction is often the result of occlusion of one or more coronary arteries. Occlusion and restenosis (re-closing of the vessel) are principal reasons that percutaneous transluminal coronary angioplasty (PTCA) may fail to provide long-term benefit. PTCA has been a popular treatment, which is less invasive than surgeries involving revascularization of the myocardium, promising a better quality of life for patients. Unfortunately, the rate of restenosis after balloon angioplasty is high (approximately 30-50% in the first year after treatment). Recent data suggest that intraluminal irradiation of coronary arteries in conjunction with balloon angioplasty and/or stent implantation reduces the proliferation of smooth muscle cells and neointima formation, thereby inhibiting restenosis. In order to study radiation dosimetry in the patient and for this therapy, dose distributions for electrons and photons, with discrete energies, were simulated for blood vessels of diameter 1.5, 3 and 4.5 mm irradiated with balloon and wire sources. Electron and photon transport was performed in a simple model representing the system used for irradiation using the MCNP 4B code (Monte Carlo N-Particles). Specific calculations for balloon and wire sources were also carried out for a few radionuclides. In this work, strengths and drawbacks conceming the use of each radionuclide simulated, as well as source geometries are discussed. The dosimetry performed in this study will improve understanding of the benefit-to-risk ratio in intracoronary brachytherapy.

Performance of dose calibrators in Brazilian hospitals for activity measurements.

In order to obtain information on the accuracy of activity measurements in Brazilian hospitals, several intercomparison exercises have been organized since 1998. The first exercise consisted of two intercomparison runs of 131I and 99mTc and had the participation of 21 hospitals localized in Rio de Janeiro city and surroundings. The second, with 131I (47 hospitals) and 123I (12 hospitals), had the participation of hospitals localized in the whole country. The results were analyzed under the statistical point of view and conformity to the norms of Regulatory Authority. These results have shown that such exercises are necessary to improve the quality of the measurements and to identify those instruments that are producing incorrect values.

Metrological capability of the Brazilian laboratories of analyses of radionuclides in environmental samples.

The metrological capability of 24 Brazilian laboratories of radionuclide determinations in environmental samples was analysed for purposes to establish requirements for accreditation of laboratory for each radionuclide. For each type of analysis, the range of activity per unit mass or volume, the range of the reference value and its correspondent uncertainty were described. The accuracy was established using the statistical criteria of USE.P.A. for the laboratory performance classification. The precision of the analyses, expressed by its variation coefficient of the laboratory determinations, was classified in intervals of 5%. The data base was constituted by 3013 results of analyses obtained in 28 intercomparison runs performed from 1991 to 2000, for K, Th, Unat, gross alpha, gross beta, and other 27 radionuclides, in matrices of water, soil, vegetation, air filter and milk. The quality criteria established were the variation coefficient less than 5% and good performance in intercomparison runs. Results included from 5% to 10% are also considered, for special types of matrices and radionuclides.

Labeling and quality control of 188Re-lanreotide.

Lanreotide was labelled with 188Re obtained from 188W/188Re generator, using stannous ion as reducing agent, ascorbic acid as stabilizers and hydroxy ethylidene bisphosphonate (HEDP) as intermediary ligand at different molar ratios, pH and incubation times. Best yields (>95%) were obtained using molar ratios SnF2/lanreotide, ascorbic/lanreotide and HEDP/lanreotide of 40, 12 and 260, respectively, pH 1-2 with an incubation at 100 degrees C for 30 min. Quality control evaluation and stability of the radiolabel compound was done by the following selected methods: chromatography in Whatman 3 MM with MEK and NaCl 0.15 M as solvents, ITLC-SG with ethanol-HCl 0.01N (90:10); reverse phase extraction cartridge (Sep-pak C18, Waters Associated) and RP-HPLC with radiometric and UV detection (220 nm) using MCH-5 n-capp column with linear gradient from 90% H2O (TFA 0.1%): 10% ACN (TFA 0.1%) up to 10% H2O (TFA 0.1%):90% ACN (TFA 0.1%) in 30 min, at flow 1 ml/min. Biodistribution in normal mice showed that 188Re-lanreotide is excreted mainly through the hepatobiliary system: more than 70% I.D. is present in gallbladder and intestines at 2 hr post injection. The stability of the 188Re-peptide bond by cysteine challenge test at 37 degrees C, during 2 and 24 hr of incubation time, reveals that approximately 300 and 100 molar ratio cys/peptide is required to displace 50% of the 188Re from the complex. In vitro stability of 188Re-lanreotide at room temperature (Rt) was demonstrated during 24 hr Future works must be done in order to investigate its binding capacity to somatostatin receptors.

Direct radiolabeling of monoclonal antibodies with rhenium-188 for radioimmunotherapy of solid tumors--a review of radiolabeling characteristics, quality control and in vitro stability studies.

188Re is one of the radioisotopes expected to emerge as useful for therapy. Development of new radiopharmaceuticals based on 188Re depends on the radiolabeling methods used, which would give stable complexes having predefined radiochemical properties and in vitro and in vivo stability. This paper has attempted to provide a perspective of 188Re-labeled monoclonal antibodies, their radiolabeling characteristics, methods for quality control of radioimmunoconjugates and in vitro stability for radioimmunotherapy of solid tumors. The direct method of 188Re radiolabeling of antibodies by reductive attachment of 188Re in which free sulfhydryl groups have been generated by reduction of the intramolecular S-S disulfide bonds has been shown to be a promising approach in particular. Moreover, excellent methods have been developed to test the radionuclide, radiochemical purity and stability of 188Re-radioimmunoconjugates using high performance liquid chromatography (HPLC) and paper chromatography.