PSMA based nuclear imaging has significantly impacted our way of handling patients with prostate cancer. Its preliminary performance in different clinical scenarios and ability to detect lesions even in low PSA values seems fairly promising and deserves to be supplemented with further clinical studies.
IntroductionCoronaviruses belonging to the family Coronaviridae from the members of the order Nidovirales are spherical, enveloped, and single-stranded positive RNA viruses within the diameter range of 60-220 nm, which have rodshaped glycoprotein extensions in their outer surfaces and carry a genome size of 26-32 kb (King et al., 2011;Shereen et al., 2020). Among the coronaviruses, which are classified into four subgroups: alpha (α), beta (β), gamma (γ), and delta (δ) (Kin et al., 2015), the strains that currently infect humans are seven; HCoV229E, HCoV-OC43, SARS-CoV, HCoV-NL63, HCoV-HKU1, MERS-CoV, and SARS-CoV-2 (severe acute respiratory syndrome coronavirus) (Nomura et al., 2004).Following the severe acute respiratory syndrome (SARS-CoV) that occurred in China in 2002, MERS-CoV caused endemic in the Middle East countries in 2013 (Brian and Baric, 2005), while SARS-CoV-2 created pandemics in 2020 1 . The SARS-1 WHO has declared COVID-19 as a pandemic. [online] Website: https://www.who.int/dg/speeches/detail/who-director-general-s-opening-remarks-at-the-media-briefing-on-covid-19---11-march-2020 [accessed date 25.05.2020]CoV-2, which caused the COVID-19 pandemic, belongs to the group of betacoronavirus and its clinical manifestations are evaluated in three different stages: i) mild; weakness, fever, dry cough, fatigue, and upper respiratory tract infections, ii) moderate; shortness of breath, severe cough, diarrhea, iii) severe; severe pneumonia, acute lung injury (ALI), and acute respiratory distress syndrome (ARDS), sepsis and septic shock (Cascella et al., 2020). Currently, there is no specific antiviral therapy developed against SARS-CoV-2.Based on previous experiences in SARS-CoV and MERS-CoV outbreaks, some treatment strategies have been developed (Cascella et al., 2020;Mehta et al., 2020;. These strategies include antiviral treatments or combinations of these that have been known to be safe for humans and used in previous viral outbreaks,
Coronavirus disease 2019 (COVID-19) is today's most serious epidemic disease threatening the human race. The initial therapeutic approach of SARS-CoV-2 disease is based upon the binding the receptor-binding site of the spike protein to the host cell's ACE-2 receptor on the plasma membrane. In this study, it is aimed to develop a biocompatible and biodegradable polymeric drug delivery system that is targeted to the relevant receptor binding site and provides controlled drug release. Oseltamivir phosphate (OP) is an orally administered antiviral prodrug for primary therapy of the disease in biochemically activated carboxylate form (oseltamivir carboxylate OC). In the presented study, model drug OP loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) targeted with spike-binding peptide 1 (SBP1) of SARS-CoV-2 were designed to be used as an efficient and prolonged released antiviral drug delivery system. RY, EE, and DL values of the OP-loaded NPs produced by the solvent evaporation method were calculated to be 59.3%, 61.4%, and 26.9%, respectively. The particle size of OP-loaded NPs and OP-loaded NPs targeted with SBP1 peptide were 162.0±11.0 and 226.9±21.4 nm, respectively. While the zeta potential of the produced OP-loaded NPs was achieved negatively −23.9±1.21 mV), the result of the modification with SBP1 peptide this value approached zero as −4.59±0.728 mV. Morphological features of the OP-loaded NPs were evaluated using FEG-SEM. The further characterization and surface modification of the NPs were analyzed by FT-IR. In-vitro release studies of NPs showed that sustained release of OP occurred for two months that fitting the Higuchi kinetic model. By evaluating these outputs, it was reported that surface modification of OP-loaded NPs was significantly effective on characteristics such as size, zeta potential values, surface functionality, and release behavior. The therapeutic model drug-loaded polymeric formulation targeted with a specific peptide may serve as an alternative to more effective and controlled release pharmaceuticals in the treatment of COVID-19 upon an extensive investigation.
Purpose 177Lu-PSMA inhibitor peptide receptor radioligand therapy (RLT) is playing an increasing role in metastatic castration-resistant prostate cancer. We aimed to estimate the absorbed radiation doses for critical organs (eg, kidneys, parotid glands, submandibular glands, and lacrimal glands) of patients treated with 4 to 6 cycles by 177Lu-PSMA inhibitor RLT, retrospectively, and to evaluate the findings extensively in order to determine the critical organ radiation-absorbed limitations and the number of prospective RLT. Materials and Methods A total of 51 cycles 177Lu-PSMA inhibitor RLT in 10 patients was analyzed. Therapies have been applied in 4 to 6 cycles with 8 to 10 weeks' intervals. Dosimetric estimates of kidneys, parotid glands, submandibular glands, and lacrimal glands have been calculated based on MIRD scheme pamphlet no. 16. Regions of interest were drawn with GE Xeleris Functional Imaging Workstation. OLINDA/EXM 1.1 simulation software was used to calculate radiation-absorbed doses. Results Mean radiation-absorbed doses were 0.70 ± 0.24 Gy/GBq for kidneys, 1.34 ± 0.78 Gy/GBq for parotid glands, 0.94 ± 0.45 Gy/GBq for submandibular glands, and 2.28 ± 1.29 Gy/GBq for lacrimal glands. Conclusions Due to the critical target organ risks and the optimal therapy doses, patient-specific dosimetry is a deterministic factor in radionuclide therapy. Even when the absorbed kidney doses were above the ICRP critical dose limits in patients who had 4 to 6 cycles of therapy, mortality due to nephrotoxicity has not been observed. Mild increased tolerated radiation dose is acceptable for the patient groups with very low survival rate.
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