16,011 research outputs found
First preclinical evaluation of [<sup>225</sup>Ac]Ac-DOTA-JR11 and comparison with [<sup>177</sup>Lu]Lu-DOTA-JR11, alpha versus beta radionuclide therapy of NETs
No full textBackground: The [177Lu]Lu-DOTA-TATE mediated peptide receptor radionuclide therapy (PRRT) of neuroendocrine tumors (NETs) is sometimes leading to treatment resistance and disease recurrence. An interesting alternative could be the somatostatin antagonist, [177Lu]Lu-DOTA-JR11, that demonstrated better biodistribution profile and higher tumor uptake than [177Lu]Lu-DOTA-TATE. Furthermore, treatment with alpha emitters showed improvement of the therapeutic index of PRRT due to the high LET offered by the alpha particles compared to beta emitters. Therefore, [225Ac]Ac-DOTA-JR11 can be a potential candidate to improve the treatment of NETs (Graphical abstract). DOTA-JR11 was radiolabeled with [225Ac]Ac(NO3)3 and [177Lu]LuCl3. Stability studies were performed in phosphate buffered saline (PBS) and mouse serum. In vitro competitive binding assay has been carried out in U2OS-SSTR2 + cells for natLa-DOTA-JR11, natLu-DOTA-JR11 and DOTA-JR11. Ex vivo biodistribution studies were performed in mice inoculated with H69 cells at 4, 24, 48 and 72 h after injection of [225Ac]Ac-DOTA-JR11. A blocking group was included to verify uptake specificity. Dosimetry of selected organs was determined for [225Ac]Ac-DOTA-JR11 and [177Lu]Lu-DOTA-JR11. Results: [225Ac]Ac-DOTA-JR11 has been successfully prepared and obtained in high radiochemical yield (RCY; 95%) and radiochemical purity (RCP; 94%). [225Ac]Ac-DOTA-JR11 showed reasonably good stability in PBS (77% intact radiopeptide at 24 h after incubation) and in mouse serum (~ 81% intact radiopeptide 24 h after incubation). [177Lu]Lu-DOTA-JR11 demonstrated excellent stability in both media (> 93%) up to 24 h post incubation. Competitive binding assay revealed that complexation of DOTA-JR11 with natLa and natLu did not affect its binding affinity to SSTR2. Similar biodistribution profiles were observed for both radiopeptides, however, higher uptake was noticed in the kidneys, liver and bone for [225Ac]Ac-DOTA-JR11 than [177Lu]Lu-DOTA-JR11. Conclusion: [225Ac]Ac-DOTA-JR11 showed a higher absorbed dose in the kidneys compared to [177Lu]Lu-DOTA-JR11, which may limit further studies with this radiopeptide. However, several strategies can be explored to reduce nephrotoxicity and offer opportunities for future clinical investigations with [225Ac]Ac-DOTA-JR11.RST/Applied Radiation & Isotope
Influence of ac ageing on space charge dynamics in LDPE
No full textPolymeric materials have been widely used as insulation in power industry due to their excellent electrical properties. However, these properties deteriorate in time irreversibly when the material is subjected to electric stress. Although space charge is believed to play an important role in ac ageing, exact mechanisms are poorly understood due to very limited experimental data. In the present work efforts have been made to investigate the influence of ac ageing on space charge dynamics in low-density polyethylene (LDPE). LDPE films with 200mm were aged at 50 kV/mm at 50 Hz for various times at ambient temperature. Space charge dynamics in the samples prior to and after ageing were monitored using the pulsed electroacoustic (PEA) technique under dc electric stress. The results indicate that there is a significant amount of homocharge accumulation in the unaged sample due to charge injection. These injected charges are the captured by the deep traps originated from the interface between crystalline and amorphous regions in LDPE. Ageing under ac condition does not necessarily lead to an increase in amount of charge in the bulk but leads to an increase in mobility of charge carriers. Chemical analysis by infrared spectroscope (FTIR) reveals there are chemical changes taken place in the bulk of the material after ac ageing. It is believed that the chemical changes introduce shallow traps which promote the movement of charge carriers in the bulk. Consequently, the injected charges spread across the sample
First preclinical evaluation of [<sup>225</sup>Ac]Ac-DOTA-JR11 and comparison with [<sup>177</sup>Lu]Lu-DOTA-JR11, alpha versus beta radionuclide therapy of NETs
No full textBackground: The [177Lu]Lu-DOTA-TATE mediated peptide receptor radionuclide therapy (PRRT) of neuroendocrine tumors (NETs) is sometimes leading to treatment resistance and disease recurrence. An interesting alternative could be the somatostatin antagonist, [177Lu]Lu-DOTA-JR11, that demonstrated better biodistribution profile and higher tumor uptake than [177Lu]Lu-DOTA-TATE. Furthermore, treatment with alpha emitters showed improvement of the therapeutic index of PRRT due to the high LET offered by the alpha particles compared to beta emitters. Therefore, [225Ac]Ac-DOTA-JR11 can be a potential candidate to improve the treatment of NETs (Graphical abstract). DOTA-JR11 was radiolabeled with [225Ac]Ac(NO3)3 and [177Lu]LuCl3. Stability studies were performed in phosphate buffered saline (PBS) and mouse serum. In vitro competitive binding assay has been carried out in U2OS-SSTR2 + cells for natLa-DOTA-JR11, natLu-DOTA-JR11 and DOTA-JR11. Ex vivo biodistribution studies were performed in mice inoculated with H69 cells at 4, 24, 48 and 72 h after injection of [225Ac]Ac-DOTA-JR11. A blocking group was included to verify uptake specificity. Dosimetry of selected organs was determined for [225Ac]Ac-DOTA-JR11 and [177Lu]Lu-DOTA-JR11. Results: [225Ac]Ac-DOTA-JR11 has been successfully prepared and obtained in high radiochemical yield (RCY; 95%) and radiochemical purity (RCP; 94%). [225Ac]Ac-DOTA-JR11 showed reasonably good stability in PBS (77% intact radiopeptide at 24 h after incubation) and in mouse serum (~ 81% intact radiopeptide 24 h after incubation). [177Lu]Lu-DOTA-JR11 demonstrated excellent stability in both media (> 93%) up to 24 h post incubation. Competitive binding assay revealed that complexation of DOTA-JR11 with natLa and natLu did not affect its binding affinity to SSTR2. Similar biodistribution profiles were observed for both radiopeptides, however, higher uptake was noticed in the kidneys, liver and bone for [225Ac]Ac-DOTA-JR11 than [177Lu]Lu-DOTA-JR11. Conclusion: [225Ac]Ac-DOTA-JR11 showed a higher absorbed dose in the kidneys compared to [177Lu]Lu-DOTA-JR11, which may limit further studies with this radiopeptide. However, several strategies can be explored to reduce nephrotoxicity and offer opportunities for future clinical investigations with [225Ac]Ac-DOTA-JR11.</p
A power sharing series power BJT array with isolated low voltage control for AC power control applications
No full textA technique for a continuously variable AC resistance using a series BJT array is presented. This array provides high power dissipation capability and uniform voltage and power distribution across the individual transistors. The array, controlled using a set of optoisolators to maintain the electrical isolation between the control circuits and the power stage, could be used as the basis to develop several useful techniques including a solid state AC regulator with comparable performance to the commonly used ferro-resonant systems; a linear AC electronic load suitable for testing UPS and other power conditioners; and, in other AC power control applications such as switching capacitors in AC resonant circuits
Experimental studies of influence of DC and AC electric fields on bridging in contaminated transformer oil
No full textAnalysis of real operating condition revealed that HVDC transformers experience combined effect of DC biased AC electric field. The dynamics of pressboard particle in contaminated transformer oil under the influence of DC, AC and DC biased AC electric field has been investigated in this paper. Different levels of particle concentrations are tested at different applied voltages. Optical images of the particles accumulation together with conduction current have been recorded during the experiments. A complete bridge between the electrodes of cellulose particles were observed for all the tests carried out under DC and DC biased AC electric field. Opposite to that, for AC experiments, pressboard particles accumulated on surfaces of both electrodes but did not create a full bridge between the electrodes. It is concluded that a combination of DC and AC voltages in a HVDC transformer could lead to a bridge formation within the equipment which could cause failure
Experimental High-Frequency Parameter Identification of AC Electrical Motors
No full textIn order to predict conducted electromagnetic interference in inverter-motor drive systems, high-frequency (HF) motor models are requested and the involved parameters have to be available. In previous studies, the authors have presented an accurate HF model for induction motors and they have defined the procedures to identify the model parameters. In this paper, these results are extended to several types and sizes of industrial ac motors such as induction, synchronous reluctance (without interior permanent magnets), and brushless motors. The model parameter-identification procedure has been improved, and it is based on a least-squares data fitting applied to the measured magnitude and phase-frequency-response curves of the phase-to-ground and the phase-to-neutral impedances. The aim of this paper is to provide quick indications to select the suitable values of the HF model parameters, with reference to the size and type of the ac motor, to evaluate the HF voltage and current components in inverted-fed ac motor system
In silico study on radiobiological efficacy of Ac-225 and Lu-177 for PSMA-guided radiotherapy.
No full textThe good efficacy of radioligand therapy (RLT) targeting prostate specific-membrane antigen (PSMA) for the treatment of metastatic castration-resistant prostate cancer (mCRPC) has been recently demonstrated in several clinical studies. However, the treatment effect of 177Lu-PSMA-ligands is still suboptimal for a significant fraction of patients. In contrast to external beam radiotherapy, the radiation dose distribution itself is strongly influenced by the heterogeneous tumour microenvironment. Although microdosimetry is critical for RLT treatment outcome, it is difficult to clinically or experimentally establish the quantitative relation. We propose an in silico approach to quantitatively investigate the microdosimetry and its influence on treatment outcome for PSMA-directed RLT of two different radioisotopes 177Lu and 225 Ac. The ultimate goal is optimize the combined 177 Lu and 225 Ac-PSMA therapy and maximize the anti-tumour effect, while minimizing irradiation of off-target tissues.Clinical relevance- With the proposed hybrid model we show that 177Lu-PSMA-ligands treatment assures a more homogeneously distributed dose and a lower dependency of the treatment outcome on the domain vascularisation. On the other hand, the 225Ac-PSMA-ligands treatment shows a much stronger efficacy in killing tumor cells with an equivalent mean dose distribution even in an hypoxic environment
Safety and efficacy of Ac-225-PSMA-617 in mCRPC after failure of Lu-177-PSMA
No full textDespite the approval of several new agents metastatic castration resistant prostate cancer is still a major medical challenge. The beta-emitting Lu-177-PSMA radioligand therapy (RLT) is a new option but its antitumor effect can decrease over time. The aim of this retrospective analysis was to investigate safety and efficacy of the alpha emitting Ac-225-PSMA-617 RLT in mCRPC after Lu-177-PSMA failure.JRC.G.I.5 - Advanced Nuclear Knowledg
Safety and efficacy of Ac-225-PSMA-617 in mCRPC after failure of Lu-177-PSMA
No full textDespite the approval of several new agents metastatic castration resistant prostate cancer is still a major medical challenge. The beta-emitting Lu-177-PSMA radioligand therapy (RLT) is a new option but its antitumor effect can decrease over time. The aim of this retrospective analysis was to investigate safety and efficacy of the alpha emitting Ac-225-PSMA-617 RLT in mCRPC after Lu-177-PSMA failure.JRC.G.I.5 - Advanced Nuclear Knowledg
Safety and efficacy of Ac-225-PSMA-617 in mCRPC after failure of Lu-177-PSMA
No full textDespite the approval of several new agents metastatic castration resistant prostate cancer is still a major medical challenge. The beta-emitting Lu-177-PSMA radioligand therapy (RLT) is a new option but its antitumor effect can decrease over time. The aim of this retrospective analysis was to investigate safety and efficacy of the alpha emitting Ac-225-PSMA-617 RLT in mCRPC after Lu-177-PSMA failure.JRC.G.I.5 - Advanced Nuclear Knowledg
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