Background/Objectives: Haloperidol is a typical antipsychotic drug widely used for acute confusional state, psychotic disorders, agitation, delirium, and aggressive behavior. Methods: The toxicity of haloperidol was studied using zebrafish (ZF) embryos as a model organism. Dechorionated embryos were exposed to various concentrations of haloperidol (0.5–6.0 mg/L). The lethal dose concentration was estimated and was found to be 1.941 mg/L. Results: The impact of haloperidol was dose-dependent and significant from 0.25 mg/L. Haloperidol induced several deformities at sublethal doses, including abnormal somites, yolk sac edema, and skeletal deformities. Haloperidol significantly affected heart rate and blood flow and induced pericardial edema and hyperemia in a dose-dependent manner, suggesting its influence on heart development and function. Embryos exposed to haloperidol during their ontogenetic development had smaller body length and eye surface area than non-exposed ones in a dose-dependent manner. Conclusions: It was found that haloperidol significantly affects the behavior of the experimental organisms in terms of mobility, reflexes to stimuli, and adaptation to dark/light conditions.

Rapid cellular assessment of cell-cycle perturbation can complement conventional developmental toxicology in zebrafish, but rapid DNA-content workflows developed for mammalian tissues require adaptation for whole embryos. Here, we applied an embryo-adapted version of rapid DNA-content flow cytometry analysis within a 96-h cisplatin exposure model in zebrafish (Danio rerio) and integrated this cellular readout with morphometric, cardiac, and neurobehavioral analysis. Dechorionated embryos were exposed to 10–400 μM cisplatin and evaluated for body length, eye surface area, heart rate, locomotor activity, thigmotaxis, touch-evoked and vibrational startle responses, and whole-embryo cell-cycle distribution. The adapted workflow combines immediate mechanical dissociation, filtration, brief propidium iodide/RNase staining, singlet gating, and direct flow cytometric acquisition. Importantly, each flow cytometry sample consisted of a single embryo, enabling DNA-content analysis at the individual-embryo level without pooling. Cisplatin produced time- and concentration-dependent growth effects and high-dose behavioral alterations, whereas heart rate was comparatively preserved. Flow cytometry detected the clearest cell-cycle redistribution at 400 μM, with a significant reduction in G0/G1 and an increase in G2/M. These findings demonstrate the practical applicability of a combined rapid embryo-adapted DNA-content workflow as a complementary cellular endpoint in a zebrafish developmental-toxicity platform and support further methodological application across experimental settings.

Glioblastoma, the most frequent malignant primary brain tumor in adults, presents a significant challenge in cancer treatment, with a mean survival of merely 12-15 months and a 5-year survival rate of less than 2%. Despite extensive research and current treatments, involving maximal surgical excision, radiation, and chemotherapy mainly with temozolomide (TMZ), recurrence remains nearly universal. This is attributable to its infiltrative nature and tumor cells may be found far from the surgical resection cav-ity. To address the critical need for improved diagnostic and therapeutic strategies for glioblastoma multiform (GBM), we have developed an innovative theranostic molecule, AGT-7, based on tetrofosmin, a compound used in nuclear medicine bioimaging, and TMZ. AGT-7 was specifically designed to enable simultaneous tumor imaging and tar-geted chemotherapy. Its diagnostic component was inspired by the ability of tetrofosmin to selectively accumulate in glioma mitochondria, driven by its positive charge and the negative membrane potential of these organelles. A chelating moiety allows for radio-labeling with technetium-99m (⁹⁹ᵐTc), enabling precise SPECT imaging. The therapeutic arm comprises a tethered TMZ moiety, delivering localized cytotoxic activity. In vitro studies demonstrated that AGT-7 exerts potent cytotoxic effects in GBM cell lines (T98 and U87), with superior therapeutic efficacy compared to TMZ alone. Toxicity assess-ment in zebrafish embryos confirmed a favorable safety profile. Furthermore, biodis-tribution studies in CFW mice showed that [⁹⁹ᵐTc]Tc-AGT-7 exhibited approximately tenfold lower heart uptake than [⁹⁹ᵐTc]Tc-tetrofosmin, a standard cardiac imaging agent, indicating a significant reduction in off-target cardiac localization. This reduced heart uptake is particularly advantageous, as it minimizes potential cardiotoxicity and en-hances the suitability of AGT-7 as a glioma-targeted theranostic agent.

Background: Glioblastoma, the most common malignant primary brain tumor in adults, continues to present a major therapeutic challenge, with a median survival of only 12–15 months and a 5-year survival rate below 2%. Despite aggressive treatment—including maximal surgical excision, radiation, and temozolomide (TMZ) chemotherapy—recurrent disease is nearly universal due to the tumor’s infiltrative nature. Objectives: To address the critical need for improved diagnostic and therapeutic strategies for glioblastoma multiforme (GBM), we have developed an innovative theranostic molecule, [^99mTc]Tc-AGT-7. Methods: AGT-7 integrates diagnostic and therapeutic modalities comprising [^99mTc]Tc-TF (a nuclear medicine imaging agent) and TMZ. The diagnostic component has been tailored to selectively accumulate in glioma mitochondria. A chelating moiety enables radiolabeling with technetium-99m (^99mTc) for precise Single-Photon Emission Computed Tomography (SPECT) imaging. The therapeutic arm includes the tethering of a TMZ moiety for localized cytotoxicity. Conclusions: In vitro studies illustrated that AGT-7 has potent cytotoxic effects in GBM cell lines (T98 and U87), with greater efficacy than TMZ, and toxicity assays in zebrafish embryos indicated a favorable safety profile. Biodistribution studies in CFW mice demonstrated that [^99mTc]Tc-AGT-7 exhibited a ~10-fold lower heart uptake compared to [^99mTc]Tc-TF, implying reduced off-target cardiac localization. This significantly lowers the risk of cardiotoxicity and enhances AGT-7’s potential as a glioma-targeted theranostic agent.