| 1. |
- Busslinger, Sarah D., et al.
(författare)
-
Comparison of the tolerability of 161Tb- and 177Lu-labeled somatostatin analogues in the preclinical setting
- 2024
-
Ingår i: EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING. - 1619-7070 .- 1619-7089.
-
Tidskriftsartikel (refereegranskat)abstract
- Purpose [Lu-177]Lu-DOTATATE is an established somatostatin receptor (SSTR) agonist for the treatment of metastasized neuroendocrine neoplasms, while the SSTR antagonist [Lu-177]Lu-DOTA-LM3 has only scarcely been employed in clinics. Impressive preclinical data obtained with [Tb-161]Tb-DOTA-LM3 in tumor-bearing mice indicated the potential of terbium-161 as an alternative to lutetium-177. The aim of the present study was to compare the tolerability of Tb-161- and Lu-177-based DOTA-LM3 and DOTATATE in immunocompetent mice. Methods Dosimetry calculations were performed based on biodistribution data of the radiopeptides in immunocompetent mice. Treatment-related effects on blood cell counts were assessed on Days 10, 28 and 56 after application of [Tb-161]Tb-DOTA-LM3 or [Tb-161]Tb-DOTATATE at 20 MBq per mouse. These radiopeptides were also applied at 100 MBq per mouse and the effects compared to those observed after application of the Lu-177-labeled counterparts. Bone marrow smears, blood plasma parameters and organ histology were assessed at the end of the study. Results The absorbed organ dose was commonly higher for the SSTR antagonist than for the SSTR agonist and for terbium-161 over lutetium-177. Application of a therapeutic activity level of 20 MBq [Tb-161]Tb-DOTA-LM3 or [Tb-161]Tb-DOTATATE was well tolerated without major hematological changes. The injection of 100 MBq of the Tb-161- and Lu-177-based somatostatin analogues affected the blood cell counts, however. The lymphocytes were 40-50% lower in treated mice compared to the untreated controls on Day 10 irrespective of the radionuclide employed. At the same timepoint, thrombocyte and erythrocyte counts were 30-50% and 6-12% lower, respectively, after administration of the SSTR antagonist (p < 0.05) while changes were less pronounced in mice injected with the SSTR agonist. All blood cell counts were in the normal range on Day 56. Histological analyses revealed minimal abnormalities in the kidneys, liver and spleen of treated mice. No correlation was observed between the organ dose and frequency of the occurrence of abnormalities. Conclusion Hematologic changes were more pronounced in mice treated with the SSTR antagonist than in those treated with the SSTR agonist. Despite the increased absorbed dose delivered by terbium-161 over lutetium-177, [Tb-161]Tb-DOTA-LM3 and [Tb-161]Tb-DOTATATE should be safe at activity levels that are recommended for their respective Lu-177-based analogues.
|
|
| 2. |
|
|
| 3. |
- Roskam, Isabelle, et al.
(författare)
-
Three reasons why parental burnout is more prevalent in individualistic countries : a mediation study in 36 countries
- 2024
-
Ingår i: Social Psychiatry and Psychiatric Epidemiology. - : Springer Nature. - 0933-7954 .- 1433-9285. ; 59, s. 681-694
-
Tidskriftsartikel (refereegranskat)abstract
- PurposeThe prevalence of parental burnout, a condition that has severe consequences for both parents and children, varies dramatically across countries and is highest in Western countries characterized by high individualism.MethodIn this study, we examined the mediators of the relationship between individualism measured at the country level and parental burnout measured at the individual level in 36 countries (16,059 parents).ResultsThe results revealed three mediating mechanisms, that is, self-discrepancies between socially prescribed and actual parental selves, high agency and self-directed socialization goals, and low parental task sharing, by which individualism leads to an increased risk of burnout among parents.ConclusionThe results confrm that the three mediators under consideration are all involved, and that mediation was higher for self-discrepancies between socially prescribed and actual parental selves, then parental task sharing, and lastly selfdi-rected socialization goals. The results provide some important indications of how to prevent parental burnout at the societal level in Western countries.
|
|
