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Abstract: Therapeutic peptides are highly potent and specific in their functions, but difficulties in their administration require parallel development of viable delivery systems to improve their bioavailability. In this study the potential of a novel lipid-based colloidal delivery system for improving the absorption of nasally and intestinally administered salmon calcitonin (sCT) was investigated. Two types of delivery vehicles based on Pheroid™ technology was prepared and characterized. Liposome-like bilayer vesicles had a mean diameter of 1.0μm and microsponges were 1.6μm. Doses of 10IU/kg and 500IU/kg bodyweight sCT were administered intranasally and intestinally to rats, respectively. The obtained absorption enhancement with Pheroid™ vesicles and Pheroid™ microsponges were also compared with the absorption enhancement obtained with N-trimethyl chitosan chloride (TMC). With the inclusion of 0.5% (w/v) TMC the maximum plasma concentration (C max) of sCT increased from 72.6±6.1pg/ml to 478.5±6.1pg/ml after nasal administration. Pheroid™ vesicles and Pheroid™ microsponges increased the C max values of sCT to 262.64±17.1pg/ml and 202.66±28.6pg/ml, respectively. The time to reach the maximum concentration (T max) was also significantly decreased from 35min to approximately 14min. Intestinal administration of Pheroid™ formulations increased the C max of sCT from 249.1±21.5pg/ml to 386.2±45.5 and 432.1±18.9pg/ml, respectively for Pheroid™ vesicles and Pheroid™ microsponges. TMC increased the C max of sCT to 738.9±277.1pg/ml. TMC and Pheroid™ technology could offer the potential to significantly improve intranasal and intestinal absorption of sCT and reduce the variability in absorption. [Copyright &y& Elsevier]

At the National Metrology Institute of South Africa (NMISA) absolute activity measurements of γ-emitting radionuclides are maintained for longevity on a secondary standard ionization chamber. Because the ionization chamber has lower gas pressure than that normally produced by the manufacturer, this paper focuses attention on explaining a normalization scheme devised to allow NMISA to make use of the manufacturer's supplied radionuclide calibration factors when necessary. The applicability of the procedure is justified through analysis of some results from a comprehensive simulation of the chamber undertaken in an independent study. Comparisons of the derived normalized calibration factors against those obtained through measurement at NMISA are made for a variety of radionuclides. • The NMISA secondary standard ionization chamber calibration process is described. • An explanation of a normalization scheme applied to manufacturer's radionuclide calibration factors is provided. • The effect of reduced current output due to depleted gas within the chamber is analyzed using simulated data. • Comparisons of the derived normalized calibration factors against those obtained through measurement for a variety of radionuclides. • Most secondary standards produced are of radionuclides for dissemination to the nuclear medicine community. [ABSTRACT FROM AUTHOR]

Introduction The short-lived radionuclides Tc-99m and F-18 are used in nuclear medicine for imaging purposes. Hospitals must accurately measure the activity of radiopharmaceuticals administered to patients with a radionuclide activity calibrator which is traceable to a national metrology institute via calibration sources. The International Reference System Transfer Instrument (SIRTI) was recently used by the International Bureau of Weights and Measures (BIPM) to measure the activity of Tc-99m and F-18 sources prepared at the National Metrology Institute of South Africa (NMISA). These on-site measurements were compared with those made with the calibrated NMISA ionisation chamber (IC). Through comparisons such as these, equivalence to international metrology institutes and quality of measurements are demonstrated. This presentation describes the comparison process. Materials and methods The SIRTI is a portable NaI(Tl) well counter used for on-site measurements of short-lived radionuclides at metrology institutes. In preparation for these comparisons, Tc-99m and F-18 were standardized by NMISA via the 4 π β γ liquid scintillation coincidence counting method. The results from the primary standardizations were transferred to the NMISA IC via primary standardized liquid sources. The current produced by gamma radiation emitted from these sources was used to determine calibration factors for Tc-99m and F-18. For the SIRTI comparisons, master solutions of Tc-99m and F-18 were prepared from new batches of material. From each master solution, one source was made for measurement with the NMISA IC and three for measurement with the SIRTI. The NMISA IC and calibrated balances were used to determine the activity concentration of each master solution. Using these values, the activities of the SIRTI sources were calculated and compared to the actual SIRTI measured activities. Results Comparison results for NMISA show agreement, within uncertainties, with the international reference values previously established for Tc-99m and F-18. Conclusion Good results from both comparisons ensure the quality of measurements and services provided via the NMISA IC for Tc-99m and F-18. [ABSTRACT FROM AUTHOR]

Introduction Radionuclide activity meters (commonly known as dose calibrators) are used to accurately measure the activity of radionuclide solutions used in nuclear medicine. Medical physicists are required to frequently check the accuracy of hospital dose calibrators by measuring calibration sources, the results of which must be within 10% accuracy to be deemed acceptable. Administering inappropriate amounts of radioactivity to a patient can result in ineffective treatment. Materials and methods The National Metrology Institute of South Africa (NMISA) is offering training to honours and fourth year medical physics students through a project on dose calibrator measurements. The objective is to identify and calculate the activity and corresponding uncertainties of a mixture of three unknown gamma emitting radionuclides contained in a solution. The student will be required to identify each radionuclide after measuring a spectrum with a high purity germanium (HPGe) detector. Using the NMISA ionisation chamber and electrometer, the student will be required to measure the current produced by gamma radiation emitted from a standard source of each of the identified radionuclides and calculate the corresponding calibration factors, with uncertainties. The student will be required to measure the total current produced by the three radionuclides over a period of one to two months and extract the activity of each radionuclide by deconvolution and using the calibration factors determined. An uncertainty budget will be compiled for each radionuclide. Results The project feasibility has been demonstrated through simulation of the current produced by a mixture of Ga-67, I-131 and Fe-59 over a period of one month. Statistical variation was included by altering the simulated total current appropriately, and an uncertainty on each data point was added, both procedures following a Gaussian distribution between 0 and 0.5%. The extracted activities showed agreement within 3 standard deviations, with 3% discrepancy from the expected values. Conclusion Students will receive relevant hands-on training, a requirement to become a medical physicist. [ABSTRACT FROM AUTHOR]

This paper reports on absolute activity measurements of iron-59 made at the National Metrology Institute of South Africa (NMISA) via 4π(LS)β–γ coincidence counting. The exercise formed part of an Asia Pacific Metrology Program (APMP) regional key comparison. Source data were analysed by the extrapolation technique for a number of gamma-ray window settings. In addition, a feasibility study was undertaken on a second technique; a non-extrapolation method based on a detection efficiency analysis. The reported activity concentration of the 59 Fe solution was determined with a relative uncertainty of 0.28% ( k =1), the uncertainty being due mainly to the rate vs. efficiency fitting process. The result from the non-extrapolation method was lower than that given by extrapolation by 0.33%, within two standard deviations. Possible reasons for the small discrepancy are discussed. [ABSTRACT FROM AUTHOR]

Abstract: The NMISA participated in the international key comparison of the pure beta-emitter Technetium-99, CCRI(II)-K2.Tc-99. The comparison solution was standardized using three methods, namely the TDCR efficiency calculation method, the CIEMAT/NIST efficiency tracing method and the 4π(LS)β–γ coincidence tracing method with Co-60 as tracer. Excellent agreement between results obtained with the three methods confirmed the applicability of the beta spectral shape given by the latest (2011) DDEP evaluation of Tc-99 decay data, rather than the earlier (2004) evaluation. [Copyright &y& Elsevier]

Abstract: The NMISA Radioactivity Standards Laboratory participated in the CCRI(II)-S9 inter-comparison of the measurement of the activity concentration of 137Cs and 40K in rice material, piloted by the KRISS. The paper describes the equipment used, the measurement set-up and data analysis. The efficiency of the detector for 137Cs and 40K was determined by comparison against a spiked standard solution, and Monte Carlo simulations performed to estimate the difference in γ-ray escape probability between the solution standard and starch (as an approximation for milled rice) due to attenuation disparities. The uncertainty budget was estimated rather conservatively, since these were the first low-level measurements performed by the NMISA using an HPGe detector. [Copyright &y& Elsevier]

Abstract: This paper reports on absolute measurements made at the NMISA by the 4π[LS]β–γ coincidence extrapolation technique, which formed part of a key comparison of activity measurements of the radionuclide lutetium-177, a beta–gamma emitter. A detection efficiency analysis based on the decay scheme indicated that the coincidence extrapolation method is feasible for extracting the source disintegration rate of 177Lu. A simulation was undertaken utilizing the efficiency equations to give an indication of the expected variation of the source count rate with efficiency for different gamma-ray windows. Both the simulation and experiment indicated that the window giving the highest counting efficiency was centered about the 208.4keV photopeak, with the data showing linear variation in the upper efficiency range. The extracted activity concentration of the 177Lu solution proved to be highly accurate, being higher than the proposed comparison reference value by 0.15%, well within one standard uncertainty (σ=0.26%) as specified by the NMISA. [Copyright &y& Elsevier]

Abstract: Twenty years ago South Africa''s Radioactivity Standards Laboratory (now operated by the NMISA) was the first to measure the activity of 55Fe by combining the triple-to-double coincidence ratio (TDCR) liquid scintillation method with theoretical efficiency formulae. The extracted activity was however found to be consistently low by about 6%. Due to improvements in both the counting system and analysis technique, it was decided to re-examine the method as applied at the NMISA. The latest results are presented and discussed, particularly with regard to a quantitative study into which vial type is better suited to obtaining accurate 55Fe activity measurements. [Copyright &y& Elsevier]

The radionuclides 99m Tc and 57 Co were standardized via absolute liquid scintillation counting techniques. We provide the first technical report on the absolute standardization of 99m Tc using 4 π (LS) e - γ coincidence counting. The low detection efficiency of low-energy conversion electrons translates into a large efficiency extrapolation range. A simulation indicated that the γ -ray interacting with the liquid scintillator introduces curvature to the count rate vs. efficiency relationship, the approximation of the functional form used for extrapolation providing the main measurement uncertainty for 99m Tc. A detection efficiency analysis for both radionuclides is presented. Results from the standardizations, and SIRTI and SIR comparison exercises are reported. [ABSTRACT FROM AUTHOR]

Abstract: The NMISA participated in the 2010 international key comparison of 241Pu, standardizing the inter-comparison solution by the TDCR efficiency calculation technique. Special attention was paid to ensure accurate efficiency calculation for this low-energy, pure beta-emitter: in particular the effect of low-energy stopping powers on the calculation of ionization quenching was assessed and an optimal value for the quench parameter, kB, was determined. In addition, phototube efficiency mismatch was accounted for by a software minimization technique. The effect of the beta spectral shape on the activity extracted from data analysis was assessed and found to be significant. Based on the results of this work we propose a new value for the average beta-particle energy. [Copyright &y& Elsevier]

The absolute activity of 18F was determined using 4 πβ − γ liquid scintillation coincidence counting using beta-efficiency extrapolation. An ionization chamber factor was determined for use during a SIRTI comparison, for which results are presented. A non-extrapolation method based on a detection efficiency analysis was also employed using an adaptation of the double-phototube coincidence efficiency for a threshold above the second monopeak. Results and uncertainty budgets for the two methods are presented and discussed. • Absolute standardization of F-18 using beta-efficiency extrapolation and-non extrapolation methods. • Liquid scintillation coincidence counting. • Double-tube efficiency adapted for threshold above second monopeak for non-extrapolation method. • Excellent agreement between the methods. [ABSTRACT FROM AUTHOR]