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.

Monte Carlo modeling provides accurate calibration factors for radionuclide activity meters.

Accurate determination of calibration factors for radionuclide activity meters is crucial for quantitative studies and in the optimization step of radiation protection, as these detectors are widespread in radiopharmacy and nuclear medicine facilities. In this work we developed the Monte Carlo model of a widely used activity meter, using the Geant4 simulation toolkit. More precisely the "PENELOPE" EM physics models were employed. The model was validated by means of several certified sources, traceable to primary activity standards, and other sources locally standardized with spectrometry measurements, plus other experimental tests. Great care was taken in order to accurately reproduce the geometrical details of the gas chamber and the activity sources, each of which is different in shape and enclosed in a unique container. Both relative calibration factors and ionization current obtained with simulations were compared against experimental measurements; further tests were carried out, such as the comparison of the relative response of the chamber for a source placed at different positions. The results showed a satisfactory level of accuracy in the energy range of interest, with the discrepancies lower than 4% for all the tested parameters. This shows that an accurate Monte Carlo modeling of this type of detector is feasible using the low-energy physics models embedded in Geant4. The obtained Monte Carlo model establishes a powerful tool for first instance determination of new calibration factors for non-standard radionuclides, for custom containers, when a reference source is not available. Moreover, the model provides an experimental setup for further research and optimization with regards to materials and geometrical details of the measuring setup, such as the ionization chamber itself or the containers configuration.

Formulation and characterization of silk fibroin films as a scaffold for adipose-derived stem cells in skin tissue engineering.

Skin substitutes are epidermal, dermal or complete bilayered constructs, composed by natural or synthetic scaffolds and by adherent cells such as fibroblasts, keratinocytes or mesenchymal stem cells. Silk fibroin is a promising polymer to realize scaffolds, since it is biocompatible, biodegradable, and exhibits excellent mechanical properties in terms of tensile strength. Moreover, fibroin can be added of others components in order to modify the biomaterial properties for the purpose. The aim of this work is to prepare silk fibroin films for adipose-derived stem cell (ADSCs) culture as a novel feeder layer for skin tissue engineering. Pectin has been added to promote the protein conformational transition and construct strength, while glycerol as plasticizer, providing biomaterial flexibility. Eighteen formulations were prepared by casting method using fibroin, pectin (range 1-10% w/w), and glycerol (range 0-20% w/w); films were characterized by Fourier transform infrared spectroscopy and differential scanning calorimetry assay, to select the optimal composition. A stable fibroin conformation was obtained using 6% w/w pectin, and the best mechanical properties were obtained using 12% w/w glycerol. Films were sterilized, and human ADSCs were seeded and cultured for 15 days. Cells adhere to the support assuming a fibroblastic-like shape and reaching confluence. The ultrastructural analysis evidences typical active-cell features and adhesion structures that promote cell anchorage to the film, thus developing a multilayered cell structure. This construct could be advantageously employed in cutaneous wound healing or where the use of ADSCs scaffold is indicated either in human or veterinary field.

Use of 65Zn as a tracer for the assessment of purification in the 68Ga-DOTANOC synthesis.

In the last years (68)Ga has got into the focus of researchers and clinicians especially for radio-labeling of biomolecules; an important characteristic of this positron emitting isotope is its availability via the (68)Ge/(68)Ga generator system: the long-lived (68)Ge (t1/2=270.8 d) produces the short-lived (68)Ga (t1/2=67.63 min) which decays to stable (68)Zn. (68)Ge breakthrough compromises (68)Ga radionuclidic purity, while (68)Zn might affect the specific activity of the radiopharmaceutical. In this paper we investigated the weight of these impurities in (68)Ga-DOTANOC synthesis. (65)Zn (t1/2=244.26d; decay mode: EC 98.3%, ß(+) 1.7%) was used as a radiotracer of stable (68)Zn; samples of the purification columns, wastes and product were recovered and measured with a calibrated HPGe gamma-ray spectrometry system. The results showed that (68)Zn competes with (68)Ga in labeling DOTANOC with a (95±2)% labeling yield; they also proved the effectiveness of the STRATA X-C cationic post-processing of the generator eluate in lowering the amount of this impurity to less than 1%. Moreover this approach, along with the purification of the final product through a STRATA X cartridge, effectively removes (68)Ge breakthrough providing a (68)Ga-DOTANOC radionuclidic purity of (99.9999986±0.0000006)%, superior to 99.9% required by the Pharmacopoeia Monograph on (68)Ga Edotreotide injection.

Effective production of 65Zn with a PET cyclotron.

Cyclotrons dedicated to the production of PET radiopharmaceuticals for clinical use can be a resource also for research in other fields of science. In the present study we assessed the feasibility of (65)Zn production via the (65)Cu(p,n)(65)Zn reaction using a 16.5 MeV GE-PETtrace biomedical cyclotron. The radioisotope (65)Zn (t(1/2)=244.26 zd; decay mode: EC 98.3%, ß(+) 1.7%) has a wide range of applications, especially in botany and agriculture; its long half life allows storage and delivery to research centers without a cyclotron on site. Natural copper foils (thickness: 100 µm; purity: >99.9%) were irradiated in a solid target station developed in our institution. The EXFOR and IAEA cross sections databases were carefully studied to optimize the irradiation setup in order to maximize the yield of the radionuclide of interest and minimize the production of isotopic impurities. We performed production runs at 20 µA for 30 min. Activity was measured using a calibrated HPGe gamma ray detector and an ionization chamber radionuclide activity meter. These measures showed the presence of two main contaminants: (63)Zn (t(1/2)=38.47 min) and (64)Cu (t(1/2)=12.7h); we produced (65)Zn with a saturation yield of (1.06 ± 0.07) GBq/µA (E(p)=12.65→10.48 MeV). The irradiated target was dissolved in 1 ml of 6N HNO(3) at the temperature of 90°C and then purified through anion exchange chromatography with BIO RAD AG 1×8 resin. The radionuclidic purity of the final solution of (65)Zn in HCl 0.005 N, expressed in activity, resulted superior to (99.921 ± 0.003) %.