succimer and Glioblastoma

N,N'-bis(2-mercaptoethyl)isophthalamide (NBMI) is a novel lipophilic heavy metal chelator and thiol redox antioxidant. This study was designed to investigate the neuroprotective activity of NBMI in U-87 MG cells exposed to lead acetate (PbAc). Cells were pretreated with NBMI for 24 h prior to a 48 h exposure to PbAc. Cell death (55%, p < 0.0001) and reduction of intracellular GSH levels (0.70-fold, p < 0.005) induced by 250 µM Pb were successfully attenuated by NBMI pretreatment at concentrations as low as 10 µM. A similar pretreatment with the FDA-approved Pb chelator dimercaptosuccinic acid (DMSA) proved ineffective, indicating a superior PKPD profile for NBMI. Pretreatment with NBMI successfully counteracted Pb-induced neuroinflammation by reducing IL-1β (0.59-fold, p < 0.05) and GFAP expression levels. NBMI alone was also found to significantly increase ferroportin expression (1.97-fold, p < 0.05) thereby enhancing cellular ability to efflux heavy metals. While no response was observed on the apoptotic pathway, this study demonstrated for the first time that necrotic cell death induced by Pb in U-87 MG cells is successfully attenuated by NBMI. Collectively these data demonstrate NBMI to be a promising neuroprotective compound in the realm of Pb poisoning.

Topics: Benzene Derivatives; Cation Transport Proteins; Cell Death; Cell Line, Tumor; Chelating Agents; Glioblastoma; Humans; Neuroinflammatory Diseases; Neuroprotective Agents; Organometallic Compounds; Succimer; Sulfhydryl Compounds

This study assessed pentavalent 99mTc-DMSA uptake in primary brain tumors and evaluated the relationship between retention and histologic malignancy.. SPECT images of the brain were obtained at 30 min and 3 hr after intravenous administration of approximately 555 MBq 99mTc(V)-DMSA in patients with brain tumors. Sixty studies were performed in 57 patients and 63 lesions were demonstrated: 11 glioblastomas, 13 anaplastic astrocytomas (Grade 3), 11 astrocytomas (Grade 2), 18 meningiomas and 10 schwannomas. Uptake ratios, retention ratio and retention index were calculated and compared with tumor histology and malignancy grade.. Approximately 95% of both benign and malignant primary brain tumors were demonstrated by 99mTc(V)-DMSA SPECT images. False negative was noted in three cases. The early uptake ratios were closely related to the tumor vascularity but had no statistically significant difference in the tumor histology or histologic malignancy. The delayed uptake ratio, retention ratio and retention index were higher in the malignant tumors than the benign tumors.. Technetium-99m(V)-DMSA washout from the tumor was highly dependent upon its histology and histologic malignancy. The delayed uptake ratio considerably reflected tumor histology and differentiated benign tumors from malignant tumors. The retention ratio and retention index significantly reflected tumor histology and histologic grade of primary brain tumors and clearly distinguished between benign and malignant tumors with statistically significant difference (p < 0.05). These results could suggest the clinical utility of 99mTc(V)-DMSA in imaging primary brain tumors and differentiating their histological malignancy grade noninvasively.

Topics: Adolescent; Adult; Aged; Astrocytoma; Brain Neoplasms; Child; Female; Glioblastoma; Glioma; Humans; Male; Meningeal Neoplasms; Meningioma; Middle Aged; Neurilemmoma; Oligodendroglioma; Organotechnetium Compounds; Radionuclide Imaging; Succimer; Technetium Tc 99m Dimercaptosuccinic Acid