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1.
Nucl Med Biol ; 128-129: 108878, 2024.
Article in English | MEDLINE | ID: mdl-38324923

ABSTRACT

OBJECTIVE: Diabetic patients often experience chronic inflammation and fibrosis in their cardiac tissues, highlighting the pressing need for the development of sensitive diagnostic methods for longitudinal assessment of diabetic cardiomyopathy. This study aims to evaluate the significance of an inflammatory marker known as translocator protein (TSPO) in a positron emission tomography (PET) protocol for longitudinally monitoring cardiac dysfunction in a diabetic animal model. Additionally, we compared the commonly used radiotracer, 18F-fluoro-2-deoxy-d-glucose (18F-FDG). METHODS: Fourteen 7-week-old female Sprague-Dawley rats were used in this study. Longitudinal PET experiments were conducted using 18F-N-2-(2-fluoroethoxy)benzyl)-N-(4-phenoxypyridin-3-yl)acetamide (18F-FEPPA) (n = 3), the TSPO radiotracer, and 18F-FDG (n = 3), both before and after the onset of diabetes. Histological and immunohistochemical staining assays were also conducted in both the control (n = 4) and diabetes (n = 4) groups. RESULTS: Results indicated a significant increase in cardiac tissue uptake of 18F-FEPPA after the onset of diabetes (P < 0.05), aligning with elevated TSPO levels observed in diabetic animals according to histological data. Conversely, the uptake of 18F-FDG in cardiac tissue significantly decreased after the onset of diabetes (P < 0.05). CONCLUSION: These findings suggest that 18F-FEPPA can function as a sensitive probe for detecting chronic inflammation and fibrosis in the cardiac tissues of diabetic animals.


Subject(s)
Diabetes Mellitus, Type 1 , Diabetic Cardiomyopathies , Humans , Rats , Female , Animals , Fluorodeoxyglucose F18 , Radiopharmaceuticals , Rats, Sprague-Dawley , Positron-Emission Tomography , Inflammation , Fibrosis , Receptors, GABA/metabolism
2.
Radiat Res ; 201(3): 197-205, 2024 Mar 01.
Article in English | MEDLINE | ID: mdl-38289696

ABSTRACT

Proton therapy has been widely applied on treating inaccessible and inoperable tumors, such as tumors deep within the brain or close to the critical brain stem. Nevertheless, the damaging effect of radiation for central nervous system (CNS) tumors is difficult to be confined within the irradiated region and has led to decline of neurological function in especially children with congenital CNS tumors. Currently, the involvement of n-methyl-d-aspartate (NMDA) receptors or secretary cytokines and chemokines in proton-induced bystander effects remains unclear. To understand the modulatory effects of NMDA receptor inhibition on the survival and proliferation of glioblastoma-derived cells, mesenchymal-like U373 cells were applied along with U87 neural glioblastoma cells for single doses of proton radiation at different LET in the presence or absence of pretreatment with memantine and/or collimation. Under collimation, neuronal tumor cells that are not directly irradiated (i.e., bystander cells) encounter similar biological effects potentially through cell coupling and synaptic transmission. Furthermore, whether proton LET plays a role in the mediation of bystander effect awaits to be elucidated. From this study, synaptic transmission was found to play differential roles in the proliferation of U373 and U87 cells after exposure to collimated radiation. Also, radiation-induced cell proliferation at the late stage was more correlated with bystander cell survival than early manifested γH2AX foci, suggesting that proton-induced glutamatergic synapse may act as a more important contributor than proton-induced direct effect on DNA double-stranded breaks to the late-stage responses of glioblastoma cells.


Subject(s)
Bystander Effect , Glioblastoma , Child , Humans , Bystander Effect/radiation effects , Receptors, N-Methyl-D-Aspartate , Glioblastoma/radiotherapy , Glioblastoma/pathology , Protons , Signal Transduction/radiation effects
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