To study the track structure of light ions, a measuring device has been developed at the Legnaro National Laboratory of INFN, which can be used to investigate separately the penumbra region of particle tracks and the trackcore region, which is a few nanometres in diameter. The device is based on single-electron counting techniques by means of a gas detector; it simulates a 'nanometre-sized' biological volume of about 20 nm in diameter that can be moved with respect to a narrow particle beam to measure the ionizationcluster-size distributions caused within the target volume by the passage of single primary particles, as a function of the impact parameter. To investigate the ionization-cluster-size formation caused by primary particles of medical interest when they penetrate through or pass by the target volume at a specified impact parameter, measurements and Monte Carlo simulations were performed for 20 MeV protons, 16 MeV deuterons, 48 MeV 6 Li-ions, 26.7 MeV 7 Li-ions and 96 MeV 12 C-ions. The detailed analysis of the resulting distributions showed that in the track-core region their shape is mainly determined by the mean free ionization path length of the primary particles, whereas in the penumbra region the shape of the distributions is almost independent of the impact parameter, and also of the particle type and velocity.
A mini-tissue-equivalent proportional-counter (TEPC) has been constructed to study the possibility to manufacture mini-counters without field-shaping tubes for radiation therapy. The mini-TEPC can be assembled with and without field-shaping tubes. It can be equipped with a mini-alpha source for a precise lineal energy calibration. After the positive conclusions of this study, a slim TEPC has been designed and constructed. The slim TEPC has an external diameter of only 2.7 mm. It has been tested with therapeutic proton beams and gamma ray sources.
Evaluation of the radioisotopic purity of technetium-99m (Tc) produced in GBq amounts by proton bombardment of enriched molibdenum-100 (Mo) 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 (Tc) present in the pertechnetate saline NaTcO 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 (Tc) injection 4801-3). Moreover, the impact of Tc 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-producedTc acquired with a mini-gamma camera was determined and compared with that obtained using technetium-99m solutions eluted from standard Mo/Tc generators. The effect of the increased image background contribution due to Compton-scattered higher-energy gamma rays (E > 200 keV), which could cause image-contrast deterioration, was also studied. It is concluded that, due to the high radionuclidic purity of cyclotron-produced Tc usingMo(p,2n)Tc 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 Tc.
The clinical translation of theranostic 177 Lu-radiopharmaceuticals based on inhibitors of the prostatespecific membrane antigen (PSMA) has demonstrated positive clinical responses in patients with advanced prostate cancer (PCa). However, challenges still remain, particularly regarding their pharmacokinetic and dosimetric properties. We developed a potential PSMA-immunotheranostic agent by conjugation of a single-chain variable fragment of the IgGD2B antibody (scFvD2B) to DOTA, to obtain a 177 Lu-labelled agent with a better pharmacokinetic profile than those previously reported. The labelled conjugated 177 Lu-scFvD2B was obtained in high yield and stability. In vitro, 177 Lu-scFvD2B disclosed a higher binding and internalization in LNCaP (PSMA-positive) compared to PC3 (negative control) human PCa cells. In vivo studies in healthy nude mice revealed that 177 Lu-scFvD2B present a favorable biokinetic profile, characterized by a rapid clearance from non-target tissues and minimal liver accumulation, but a slow wash-out from kidneys. Micro-SPECT/CT imaging of mice bearing pulmonary microtumors evidenced a slow uptake by LNCaP tumors, which steadily rose up to a maximum value of 3.6 SUV at 192 h. This high and prolonged tumor uptake suggests that 177 Lu-scFvD2B has great potential in delivering ablative radiation doses to PSMA-expressing tumors, and warrants further studies to evaluate its preclinical therapeutic efficacy. Background. Prostate cancer (PCa) is the second leading cause of cancer deaths for adult men in the Western world. Although radical prostatectomy and local radiotherapy are largely successful for patients with localized cancer, available treatments for metastatic PCa have demonstrated weak curative efficacy 1. Consequently, new tools to improve the detection of recurrent PCa, and particularly to identify and treat distant metastases, are imperatively needed. The prostate-specific membrane antigen (PSMA) is one of the most promising targets for the development of PCa theranostic agents. PSMA is overexpressed in 95% of prostate cancers and its expression levels progressively increase in high-grade tumors and in metastatic disease, up to 1,000 times more than in normal cells 2. Among the several PSMA-targeting molecules that have been developed, the radiolabeled Glu-ureido-based PSMA inhibitors are gaining much interest due to their high uptake by PSMA-positive cancer cells, and low background and excellent contrast in cancer imaging, even in small metastases 3,4. Theranostic agents such as 177 Lu-PSMA-617,
47Sc is one of the most promising theranostic radionuclides, thanks to its low energy γ-ray emission (159 keV), suitable for single photon emission computed tomography imaging and its intense β − emission, useful for tumour treatment. Despite promising preclinical results, the translation of 47Sc-therapeutic agents to the clinic is hampered by its limited availability. Among different 47Sc-production routes currently being investigated, the natV(p,x)47Sc reaction has proved to be of particular interest, thanks to the low-cost and easy availability on the market of natV material and the diffusion of medium energy proton cyclotrons. However, the cross section of this specific nuclear reaction is quite low and small amounts of Sc-contaminants are co-produced at energies E P ≤ 45 MeV, namely 48Sc and 46Sc. The main concern with these Sc-contaminants is their contribution to the patient absorbed dose. For such a reason, the absorbed dose contributions to healthy organs and the effective dose contributions by the three radioisotopes, 48Sc, 47Sc and 46Sc, were evaluated using DOTA-folate conjugate (cm10) as an example of radiopharmaceutical product. Considering as acceptable the limits of 99% for the radionuclidic purity and 10% for the contribution of radioactive Sc-contaminants to the total effective dose after 47Sc-cm10 injection, it was obtained that proton beam energies below 35 MeV must be used to produce 47Sc through irradiation of a natV target.
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