Nephroprotective effects of enalapril after [177Lu]-DOTATATE therapy using serial renal scintigraphies in a murine model of radiation-induced nephropathy

Background: Radiation-induced nephropathy is still dose limiting in radionuclide therapy of neuroendocrine tumors. We investigated the nephroprotective potential of the angiotensine converting enzyme inhibiting drug enalpril after [177Lu]-DOTATATE therapy in a murine model of radiation-induced nephropathy by renal scintigraphy. At first, the appropriate therapy activity to induce nephropathy was identified. Baseline scintigraphy (n = 12) entailed 12-min dynamic acquisitions after injection of 25 MBq [99mTc]-MAG3, which was followed by radionuclide therapy at four escalating activities of [177Lu]-DOTATATE: group (Gp) 1: 10 MBq;Gp 2: 20 MBq;Gp 3: 40 MBq;Gp 4: 65 MBq. Follow-up [99mTc]-MAG3 scintigraphy was carried out at days 9, 23, 44, and 65. The treatment activity for the intervention arm was selected on the basis of histological examination and declining renal function. In the second part, daily administration by gavage of 10 mg/kg/d enalapril or water (control group) was initiated on the day of radionuclide therapy. Follow-up scintigraphy was carried out at days 9, 23, 44, 65, and 86. We also created a non-therapy control group to detect therapy-independent changes of renal function over time. For all scintigraphies, mean renogram curves were analyzed and the "fractional uptake rate" (FUR;%I.D./min +/- SEM) of the tracer by the kidneys was calculated as an index of renal clearance. Results: At day 65 of follow-up, no significant change in the FUR relative to baseline (11.0 +/- 0.3) was evident in radionuclide therapy groups 1 (11.2 +/- 0.5) and 2 (10.1 +/- 0.6), but FUR was significantly reduced in groups 3 (8.93 +/- 0.6, p < 0.05) and 4 (6.0 +/- 0.8, p < 0.01);we chose 40 MBq [177Lu]-DOTATATE (Gp 3) for the intervention study. Here, at the last day of follow-up (day 86), FUR was unaltered in enalapril-treated mice (11.8 +/- 0.5) relative to the baseline group (12.4 +/- 0.3) and non-therapy group (11.9 +/- 0.8), whereas FUR in the control group had undergone a significant decline (9.3 +/- 0.5;p < 0.01). Histological examination revealed prevention of kidney damage by enalapril treatment. Conclusions: Treatment with enalapril is effective for nephroprotection during radionuclide therapy with [177Lu]-DOTATATE in mice. Although these results are only limitedly transferable to human studies, enalapril might serve as a promising drug in the mitigation of nephropathy following treatment with [177Lu]-DOTATATE

Dosimetry and optimal scan time of 18FSiTATE-PET/CT in patients with neuroendocrine tumours

PURPOSE Radiolabelled somatostatin analogues targeting somatostatin receptors (SSR) are well established for combined positron emission tomography/computer tomography (PET/CT) imaging of neuroendocrine tumours (NET). 18FSiTATE has recently been introduced showing high image quality, promising clinical performance and improved logistics compared to the clinical reference standard 68Ga-DOTA-TOC. Here we present the first dosimetry and optimal scan time analysis. METHODS Eight NET patients received a 18FSiTATE-PET/CT (250 ± 66~MBq) with repeated emission scans (10, 30, 60, 120, 180~min after injection). Biodistribution in normal organs and SSR-positive tumour uptake were assessed. Dosimetry estimates for risk organs were determined using a combined linear-monoexponential model, and by applying 18F S-values and reference target masses for the ICRP89 adult male or female (OLINDA 2.0). Tumour-to-background ratios were compared quantitatively and visually between different scan times. RESULTS After 1 h, normal organs showed similar tracer uptake with only negligible changes until 3 h post-injection. In contrast, tracer uptake by tumours increased progressively for almost all types of metastases, thus increasing tumour-to-background ratios over time. Dosimetry resulted in a total effective dose of 0.015 ± 0.004~mSv/MBq. Visual evaluation revealed no clinically relevant discrepancies between later scan times, but image quality was rated highest in 60 and 120~min images. CONCLUSION 18FSiTATE-PET/CT in NET shows overall high tumour-to-background ratios from 60 to 180~min after injection and an effective dose comparable to 68Ga-labelled alternatives. For clinical use of 18FSiTATE, the best compromise between image quality and tumour-to-background contrast is reached at 120~min, followed by 60~min after injection

THE RIGHT TO ONE'S IMAGE, AS A RIGHT OF THE HUMAN PERSONALITY JURISPRUDENCE: Received: 17th October 2023; Revised: 25th October 2023, 07th November 2023; Accepted: 19th December 2023

Through a theoretical and practical approach, the study presents the main regulations of the right to image, as a personal non-patrimonial right: the Romanian Civil Code, the Romanian Constitution, and the new legislation in the field of personal data. The study presents practical issues such as jurisprudential solutions in Romania regarding the violation of the right to image in the online environment (Facebook, Instagram), television shows, and press articles. Also, the study deals with the much-disputed issues of using the person's image in the procedures for sanctioning the employees, analyzing how the National Authority for Supervision of Personal Data Processing (N.A.S.P.D.P.) from Romania sanctioned the abuses of the employers. The case studies and the analysis of European and Romanian legislation are also useful to students, theoreticians, and legal practitioners

XRD Investigation of Some Thermal Degraded Starch Based Materials

The thermal degradation of some starch based materials was investigated using XRD method. The samples were obtained by thermal extrusion of mixtures of different proportions of starch, glycerol, and water. Such materials are suitable for the manufacturing of low pollutant packaging. Thermal degradation is one of the simplest ways to destroy such materials and this process is followed by structural modification of the local ordering of samples, water evaporation, crystallization, oxidation, or destruction of the chemical bonds. These modifications need to be studied in order to reduce to the minimum production of pollutant residues by burning process. XRD measurements show modification of the local ordering of the starch molecules depending on the temperature and initial composition of the samples. The molecular ordering perturbation is more pronounced in samples with low content of starch

Positron emission tomography in the assessment of left ventricular function in healthy rats: A comparison of four imaging methods

Objective To measure left ventricular (LV) function parameters in heart of healthy rats by three different positron emission tomography (PET) imaging techniques and by magnetic resonance imaging (MRI). Methods ECG-gated microPET examinations were obtained in seven healthy rats with 2-deoxy-2-[18F]fluoro-d-glucose (FDG) for calculation of LV-function from the blood-pool phase of the dynamic recording (FDGBP), and also from the later myocardial uptake (FDGMyo). On subsequent days, we re-measured LV-function using the novel blood-pool tracer 68Ga-albumin (AlbBP) and again by FDG (FDGMyo2) in one setting. Cine-MRI examination provided the reference standard measurement. Results The mean LV ejection fractions (LVEF) were 56 ± 3 (FDGBP), 55 ± 3 (FDGMyo), 56 ± 3 (FDGMyo2), 57 ± 3 (AlbBP), and 57 ± 2 (MRI). There were good to excellent correlations found between the LVEF-values as compared to MRI reference standard for FDGBP (r = 0.71), FDGMyo (r = 0.86) and AlbBP (r = 0.88). Both of the blood-pool methods significantly overestimated the magnitudes of end-diastolic-volume and end-systolic-volume, whereas FDGMyo matched closely to the MRI reference standard. There was no significant bias for both blood-pool methods and a minor negative bias for FDGMyo regarding the LV ejection fraction (LVEF) when compared to cine-MRI results. There was no significant difference between the means of FDGMyo and FDGMyo2 (P = .50). Conclusions Relative to reference standard MRI measurements of LVEF, there was excellent agreement between PET-based measurements, notably for the novel blood-pool tracer 68Ga-albumin

In Vivo Monitoring of Parathyroid Hormone Treatment after Myocardial Infarction in Mice with [68Ga]Annexin A5 and [18F]Fluorodeoxyglucose Positron Emission Tomography

[68Ga]Annexin A5 positron emission tomography (PET) reveals the externalization of phosphatidylserine as a surrogate marker for apoptosis. We tested this technique for therapy monitoring in a murine model of myocardial infarction (MI) including parathyroid hormone (PTH) treatment. MI was induced in mice, and they were assigned to the saline or the PTH group. On day 2, they received [68Ga]annexin A5 PET or histofluorescence TUNEL staining. Mice had 2-deoxy-2-[18F]fluoro-D-glucose (FDG)-PET examinations on days 6 and 30 for calculation of the left ventricular ejection fraction and infarct area. [68Ga]Annexin A5 uptake was 7.4 ± 1.3 %ID/g within the infarction for the controls and 4.5 ± 1.9 %ID/g for the PTH group (p = .013). TUNEL staining revealed significantly more apoptotic cells in the infarct area on day 2 in the controls (64 ± 9%) compared to the treatment group (52 ± 4%; p = .045). FDG-PET revealed a significant decrease in infarct size in the treatment group and an increase in the controls. Examinations of left ventricular ejection fraction on days 6 and 30 did not reveal treatment effects. [68Ga]Annexin A5 PET can detect the effects of PTH treatment as a marker of apoptosis 2 days after MI; ex vivo examination confirmed significant rescue of myocardiocytes. FDG-PET showed a small but significant reduction in infarct size but no functional improvement

Temporal changes in phosphatidylserine expression and glucose metabolism after myocardial infarction: An in vivo imaging study in mice

Positron emission tomography (PET) for in vivo monitoring of phosphatidylserine externalization and glucose metabolism can potentially provide early predictors of outcome of cardioprotective therapies after myocardial infarction. We performed serial [68Ga]annexin A5 PET (annexin-PET) and [18F]fluorodeoxyglucose PET (FDG-PET) after myocardial infarction to determine the time of peak phosphatidylserine externalization in relation to impaired glucose metabolism in infracted tissue. Annexin- and FDG-PET recordings were obtained in female (C57BL6/N) mice on days 1 to 4 after ligation of the left anterior descending (LAD) artery. [68Ga]annexin A5 uptake (%ID/g) in the LAD artery territory increased from 1.7 ± 1.1 on day 1 to 5.0 ± 3.3 on day 2 and then declined to 2.0 ± 1.4 on day 3 (p = .047 vs day 2) and 1.6 ± 1.4 on day 4 (p = .014 vs day 2). These results matched apoptosis rates as estimated by autoradiography and fluorescein staining. FDG uptake (%ID/g) declined from 28 ± 14 on day 1 to 14 ± 3.5 on day 4 (p < .0001 vs day 1). Whereas FDG-PET revealed continuous loss of cell viability after permanent LAD artery occlusion, annexin-PET indicated peak phosphatidylserine expression at day 2, which might be the optimal time point for therapy monitoring