Radioisotopic purity and imaging properties of cyclotron-produced 99mTc using direct 100Mo(p,2n) reaction.

Evaluation of the radioisotopic purity of technetium-99m (99mTc) produced in GBq amounts by proton bombardment of enriched molibdenum-100 (100Mo) metallic targets at low proton energies (i.e. within 15-20 MeV) is conducted. This energy range was chosen since it is easily achievable by many conventional medical cyclotrons already available in the nuclear medicine departments of hospitals. The main motivation for such a study is in the framework of the research activities at the international level that have been conducted over the last few years to develop alternative production routes for the most widespread radioisotope used in medical imaging. The analysis of technetium isotopes and isomeric states (9xTc) present in the pertechnetate saline Na99mTcO4 solutions, obtained after the extraction/purification procedure, reveals radionuclidic purity levels basically in compliance with the limits recently issued by European Pharmacopoeia 9.3 (2018 Sodium pertechnetate (99mTc) injection 4801-3). Moreover, the impact of 9xTc contaminant nuclides on the final image quality is thoroughly evaluated, analyzing the emitted high-energy gamma rays and their influence on the image quality. The spatial resolution of images from cyclotron-produced 99mTc acquired with a mini-gamma camera was determined and compared with that obtained using technetium-99m solutions eluted from standard 99Mo/99mTc generators. The effect of the increased image background contribution due to Compton-scattered higher-energy gamma rays (E γ > 200 keV), which could cause image-contrast deterioration, was also studied. It is concluded that, due to the high radionuclidic purity of cyclotron-produced 99mTc using 100Mo(p,2n)99mTc reaction at a proton beam energy in the range 15.7-19.4 MeV, the resulting image properties are well comparable with those from the generator-eluted 99mTc.

In-house cyclotron production of high-purity Tc-99m and Tc-99m radiopharmaceuticals.

In the last years, the technology for producing the important medical radionuclide technetium-99m by cyclotrons has become sufficiently mature to justify its introduction as an alternative source of the starting precursor [99mTc][TcO4]- ubiquitously employed for the production of 99mTc-radiopharmaceuticals in hospitals. These technologies make use almost exclusively of the nuclear reaction 100Mo(p,2n)99mTc that allows direct production of Tc-99m. In this study, it is conjectured that this alternative production route will not replace the current supply chain based on the distribution of 99Mo/99mTc generators, but could become a convenient emergency source of Tc-99m only for in-house hospitals equipped with a conventional, low-energy, medical cyclotron. On this ground, an outline of the essential steps that should be implemented for setting up a hospital radiopharmacy aimed at the occasional production of Tc-99m by a small cyclotron is discussed. These include (1) target production, (2) irradiation conditions, (3) separation/purification procedures, (4) terminal sterilization, (5) quality control, and (6) Mo-100 recovery. To address these issues, a comprehensive technology for cyclotron-production of Tc-99m, developed at the Legnaro National Laboratories of the Italian National Institute of Nuclear Physics (LNL-INFN), will be used as a reference example.

Diagnostic sensitivity of Tc-99m HYNIC PSMA SPECT/CT in prostate carcinoma: A comparative analysis with Ga-68 PSMA PET/CT.

BACKGROUND: Emerging data from published studies are demonstrating the superiority of Ga-68 PSMA PET/CT imaging in prostate cancer. However, the low yield of the Ge-68/Ga-68 from which Gallium-68 is obtained and fewer installed PET/CT systems compared to the SPECT imaging systems may limit its availability. We, therefore, evaluated in a head-to-head comparison, the diagnostic sensitivity of Ga-68 PSMA PET/CT and Tc-99m PSMA SPECT/CT in patients with prostate cancer. METHODS: A total of 14 patients with histologically confirmed prostate cancer were prospectively recruited to undergo Ga-68 PSMA PET/CT and Tc-99m HYNIC PSMA SPECT/CT. The mean age of patients was 67.21 ± 8.15 years and the median PSA level was 45.18 ng/mL (range = 1.51-687 ng/mL). SUVmax of all lesions and the size of lymph nodes with PSMA avidity on Ga-68 PSMA PET/CT were determined. Proportions of these lesions detected on Tc-99m HYNIC PSMA SPECT/CT read independent of PET/CT findings were determined. RESULTS: A total of 46 lesions were seen on Ga-68 PSMA PET/CT localized to the prostate (n = 10), lymph nodes (n = 24), and bones (n = 12). Of these, Tc-99m HYNIC PSMA SPECT/CT detected 36 lesions: Prostate = 10/10 (100%), lymph nodes = 15/24 (62.5%), and bones = 11/12 (91.7%) with an overall sensitivity of 78.3%. Lesions detected on Tc-99m HYNIC PSMA SPECT/CT were bigger in size (P < 0.001) and had higher SUVmax (P < 0.001) as measured on Ga-68 PSMA PET/CT compared to those lesions that were not detected. All lymph nodes greater than 10 mm in size were detected while only 28% of nodes less than 10 mm were detected by Tc-99m HYNIC PSMA SPECT/CT. In a univariate analysis, Lymph node size (P = 0.033) and the SUVmax of all lesions (P = 0.007) were significant predictors of lesion detection on Tc-99m HYNIC PSMA SPECT/CT. CONCLUSION: Tc-99m HYNIC PSMA may be a useful in imaging of prostate cancer although with a lower sensitivity for lesion detection compared to Ga-68 PSMA PET/CT. Its use is recommended when Ga-68 PSMA is not readily available, in planning radio-guided surgery or the patient is being considered for radio-ligand therapy with Lu-177 PSMA. It performs poorly in detecting small-sized lesions hence its use is not recommended in patients with small volume disease.

The concept of minimum detectable activity of radionuclide activity meters and their suitability for routine quality control of radiopharmaceuticals. An experimental study.

Radionuclide activity meters ("dose calibrators") are ionization chambers designed to measure relatively high amount of activities which are normally contained in radiopharmaceuticals. However, in the current radiopharmacy practice, these radiation detectors have been proposed to be used in measurements of samples with lower activity, such as in routine quality control (QC) tests. To check the feasibility of such measurements, in this work we assessed the performance of four different devices in the lower range of detectability, by means of experimental measurements of a radioactive sample. Accuracy and precision of each device was evaluated as a function of the activity contained in the sample in order to estimate a threshold value, or minimum detectable activity (MDA), which, according to our operational definition, may be used to express the concept of Limit of Quantification (LoQ). Moreover, a generalized procedure for the estimation of the MDA was established, which, being device- and radionuclide-independent, it may be adopted by every laboratory. Our results showed a significant variability in the MDA achieved by different activity meters. Hence a single QC test may result feasible with one specific instrument, and not with another one. Moreover, feasibility depends also on the confidence level required for each test. For these reasons, each activity meter should be qualified for its MDA or LoQ by each laboratory according to a procedure such as that described in this paper.

Renewing the radiopharmaceutical accuracy check service for Canadian radionuclide calibrators.

From 1986 to 2000, a fraction of the Canadian nuclear medicine community participated in a service offered by the National Research Council (NRC) of Canada to check the accuracy of administered doses of radiopharmaceuticals. The NRC renewed this service in recent years with a revalidation and reviving of the Secondary Standard Ionizing Radiation Chamber System (SSIRCS). The NRC conducted mock services for (99m)Tc, in varying geometries (syringes and serum vials), on two NRC commercial radionuclide calibrators, and at a nuclear medicine department in Canada. These tests showed the measured doses to be within 10% of the prepared standard but in some cases were sufficiently different from unity to warrant specific geometry factors to be derived.

Preparation of proton rich radionuclides in support of radiochemical analysis.

The production of proton rich radionuclides supports a wide range of radiochemical analyses via radioactive yield tracers ((95m)Tc and (236)Pu). In recent years, NPL and the University of Birmingham cyclotron have collaborated to produce these, and other, radionuclides.

Standardization of (99m)Tc by means of a software coincidence system.

The procedure followed by the Nuclear Metrology Laboratory, at IPEN, for the primary standardization of (99m)Tc is described. The primary standardization has been accomplished by the coincidence method. The beta channel efficiency was varied by electronic discrimination using a software coincidence counting system. Two windows were selected for the gamma channel: one at 140 keV gamma-ray and the other at 20 keV X-ray total absorption peaks. The experimental extrapolation curves were compared with Monte Carlo simulations by means of code ESQUEMA.

Comparison of (99m)Tc activity measurements at the KRISS using the new SIRTI of the BIPM.

In 2010, a comparison of activity measurements of (99m)Tc was carried out at the KRISS using the BIPM's Transfer Instrument of the International Reference System (SIRTI). The transfer instrument and the KRISS coincidence measurement method are briefly described. The degrees of equivalence with the key comparison reference value and between the present KRISS result and the earlier participants in the SIRTI and SIR comparisons have been evaluated. World-wide consistency of activity measurements of (99m)Tc is demonstrated.

Comparison of activity measurements in nuclear medicine services in Pernambuco

Intercomparison is an important tool for quality assessment, because equipment performance and procedures are evaluated and compared. In nuclear medicine, this tool is wide utilized to evaluate the ability of the services to measure activities of radiopharmaceuticals which will be administered to the patients in diagnostic or therapeutic procedures. In this work, a comparison program of activity measurements of the 99mTc, 131I, 67Ga and 201Tl radionuclides was established in Pernambuco State, at the Brazilian Northeast, with the aim of evaluating the quality of routine measurements carried out in the NMS. The results in each NMS are sent to the Standard laboratory, which compares these results with the acceptance limits recommended by national regulations. All NMS participants complied with the limit established for the accuracy of measurement (+/-10 percent) and showed that their radionuclide calibrators are adequate for measurement of the activities of radiopharmaceuticals.

A intercomparação é uma importante ferramenta para avaliação da qualidade da medição da atividade de radiofármaco, porque não apenas o desempenho do equipamento é verificado, mas também todo procedimento de medição. Na medicina nuclear, esta ferramenta é amplamente utilizada para avaliar a habilidade dos serviços de medicina nuclear (SMN) na medição da atividade dos radiofármacos que serão administrados aos pacientes para diagnósticos ou procedimentos terapêuticos. Neste trabalho, um programa de intercomparação de medidas de atividades de radiofármacos, utilizando as fontes de 99mTc, 131I, 67Ga e 201Tl, foi estabelecido no estado de Pernambuco, região nordeste do Brasil, com o objetivo de avaliar a qualidade das medições realizadas nos SMN. Os resultados obtidos em cada SMN são enviados ao laboratório padrão, que os compara com os valores de referência recomendados pela norma nacional, verificando o desempenho destes instrumentos. Todos os SMN participantes respeitaram os limites estabelecidos para a exatidão das medidas (+/-10 por cento), demonstrando que os calibradores de radionuclídeos estão adequados/apropriados para a medição de atividades de radiofármacos.

Standardization of 99mTc and 99Mo by the use of a 4pibeta-4pigamma counter.

Technetium-99m is widely used for many diagnostic investigations in nuclear medicine, thus the standardization of this nuclide is important. In classical 4pibeta-gamma coincidence counting of (99m)Tc, the steep slope of the efficiency function and the large extrapolation range may cause a large measurement uncertainty. In order to overcome these difficulties, we apply the 4pibeta+4pigamma sum counting technique for the standardization. Furthermore, we adopt both the 4pibeta-4pigamma coincidence counting method and the 4pibeta+4pigamma sum counting technique for the standardization of its parent nuclide (99)Mo. High efficiencies for both nuclides were easily achieved by the use of our 4pibeta-4pigamma counter. All the results were consistent with the reference value obtained by the conventional method obtained by NMIJ.

Investigation into the standardization of 99Tc.

The standardization of (99)Tc by several primary methods was investigated. This was performed to support a new (99)Tc transfer standard that has been developed and will be disseminated by the National Institute of Standards and Technology (NIST) as Standard Reference Material SRM 4288B. The standardization for the (99)Tc content of the solution was based on 4pibeta liquid scintillation (LS) measurements with (3)H-standard efficiency tracing (CIEMAT/NIST method). Confirmatory determinations were performed by 4pibeta(LS)-gamma(NaI) live-timed anti-coincidence (LTAC) counting and an LS-based 4pibeta triple-to-double coincidence ratio (TDCR) method.

Comparison for quality assurance of (99m)Tc activity measurements with radionuclide calibrators.

In 2005, the Physikalisch-Technische Bundesanstalt (PTB) and the QSA Global GmbH (QSA) organised a national comparison of (99m)Tc solution measurements. The purpose of this comparison was to gain information on the quality of routine activity measurements carried out in the field of nuclear medicine in Germany. In addition to this, an ampoule containing a calibrated (99m)Tc solution was sent from PTB to the Bureau International des Poids et Mesures (BIPM) to have the activity result entered into the database of the International Reference System (SIR), and thus demonstrating traceability of the measurements to the SI. In the following, we will report on the activity standardisation carried out at the PTB, and on the way in which the national comparison had been organised, and we will provide information on the analysis as well as on its results.

Experimental determination of the radionuclide calibrator setting for Technesium-99m, by using a primary standardisation method.

BACKGROUND: A new 99mTc national standard has been developed at the Italian National Metrology Institute for Ionizing Radiation quantities of ENEA (ENEA-INMRI). METHODS: The stock radioactive solution was prepared at the Ospedale Pediatrico Bambino Gesù (OPBG) and standardized at the ENEA-INMRI by using the 4pigamma absolute measurement method. The new standard was used to calibrate the dose calibrator of the OPBG Nuclear Medicine Unit (NMU) and the ENEA-INMRI portable ionization chamber which was employed as the secondary standard measurement system to calibrate the dose calibrator of another Italian nuclear medicine unit. RESULTS AND CONCLUSION: Remarkable improvement of measurement accuracy was achieved. The importance of traceable calibrations is underlined. Specific comments are made about quality control performance and measurement accuracy for the instrumentation used in nuclear medicine units of paediatric hospitals.

Half-life measurement of 95mTc--refinement in the uncertainty value.

Measurements at Isotope Products Laboratories (IPL) carried out with a hyper-pure germanium (HPGe) spectrometer have sought to improve upon the accepted half-life value for 95mTc. The uncertainty associated with the currently accepted value of (61+/-2) days allows for potentially significant improvement. Through a series of 65 measurements over the course of nearly 2 years, using multiple source-to-detector counting distances and multiple reference photopeaks, the authors have determined a half-life that agrees with the current value while reducing the uncertainty of the value by 25-fold.

Standardization of 99mTc.

The radioactivity of 99mTc was standardized by the 4piPC-gamma coincidence method with two different modes. One is using coincidences between (119.5-142.6)keV conversion electrons and K X-rays, and the other is coincidences between the 2.13 keV conversion electrons and 140.5 keVgamma-rays. The background of the K X-ray peak and the sensitivity of the proportional counter (PC) to 140 keV gamma-rays were the main sources of uncertainties in the first case and low detection efficiency for conversion electrons in the second case. General coincidence equations were written, with specific forms, for the three measurement variants, including literature variant. Comparison with the ionization chamber calibration is reported.

Quality control validation for exogenous natural surfactant labeled with 99mTc.

OBJECTIVE: Exogenous natural surfactant (ENS) labeled with 99mTc shows an elevated lung specificity allowing the acquisition of high-quality images for ventilation scintigraphy. METHODS: The methods for 99mTc-ENS quality control (physical properties, pH determination, radiochemical studies, and biologic studies) were evaluated and validated. RESULTS: The physical properties of the nonradioactive precursor and of the radiopharmaceutical were analyzed as general descriptors of the product. The pH of the radiopharmaceutical was determined by using pH test papers, a method described and validated in the United States Pharmacopeia. Chromatographic studies performed using the acetone/Whatman-1 paper system were validated as a method to evaluate the radiochemical purity of the 99mTc-ENS. Biodistribution studies on rats after intratracheal administration were validated as a method to estimate the radiopharmaceutical biodistribution in humans. CONCLUSION: The proposed method for 99mTc-ENS quality control studies and stability studies was evaluated and validated following international standards.

The use of molecular sieves to produce point sources of radioactivity.

We have used commercially available molecular sieves (zeolites) to adsorb radioactivity onto small (approximately 2.1 mm diameter) beads for use in various applications in nuclear medicine. Soaking the beads in [99mTc]-NaTcO4 solution of approximately 3 GBq ml(-1) for 1-2 min can produce point sources containing 3-6 MBq total. Radioactive uptake was strongly dependent on bead size. We have employed the sources for gamma camera uniformity and as point source markers for interactive identification of anatomical landmarks. Due to their small size (<< system spatial resolution), relatively high uptake and negligible scattering contribution they provide excellent devices with which to measure spatial resolution, detector uniformity and energy resolution. The molecular sieves are inexpensive and readily usable with both single photon and positron emitting radionuclides.

Calculation of 18F, 99mTc, 111In and 123I calibration factor using the penelope ionization chamber simulation method.

A new method using the Monte Carlo code PENELOPE for ionization chamber simulation has already been successfully used for calculating calibration factors needed for the measurements of radionuclides with photon emission (2003, Appl. Radiat. Isot., to be published). This work has been continued at (Laboratoire National Henri Becquerel) in order to calculate the calibration factors for radionuclides with short half-lives used in medical services. Activity measurements of 18F, 99mTc,111In and 123I using the calculated calibration factors were obtained with standard uncertainties equal to 0.6% for 18F, 99mTc and 1.5% for 111In and 123I.

Secondary standardisation of 95mTc.

The radionuclide 95mTc, which has a half-life of 61(2)days and emits a number of gamma-rays, may be used in radiochemical analysis as a yield tracer for the long-lived fission product 99Tc. In this work, we present (i) the production of 95mTc via an (alpha, 2n) reaction with stable 93Nb (a method which does not result in the production of any 97mTc, 98Tc or 99Tc), (ii) the chemical separation of 95mTc from niobium via coprecipitation, liquid-liquid extraction and liquid chromatography, and (iii) the secondary standardisation of 95mTc with high-resolution gamma-ray spectrometry and an ionisation chamber system.