GH acts in numerous organs expressing the GH receptor (GHR), including the brain. However, the mechanisms behind the brain's permeability to GH and how this hormone accesses different brain regions remain unclear. It is well-known that an acute GH administration induces phosphorylation of the signal transducer and activator of transcription 5 (pSTAT5) in the mouse brain. Thus, the pattern of pSTAT5 immunoreactive cells was analyzed at different time points after IP or intracerebroventricular GH injections. After a systemic GH injection, the first cells expressing pSTAT5 were those near circumventricular organs, such as arcuate nucleus neurons adjacent to the median eminence. Both systemic and central GH injections induced a medial-to-lateral pattern of pSTAT5 immunoreactivity over time because GH-responsive cells were initially observed in periventricular areas and were progressively detected in lateral brain structures. Very few choroid plexus cells exhibited GH-induced pSTAT5. Additionally, Ghr mRNA was poorly expressed in the mouse choroid plexus. In contrast, some tanycytes lining the floor of the third ventricle expressed Ghr mRNA and exhibited GH-induced pSTAT5. The transport of radiolabeled GH into the hypothalamus did not differ between wild-type and dwarf Ghr knockout mice, indicating that GH transport into the mouse brain is GHR independent. Also, single-photon emission computed tomography confirmed that radiolabeled GH rapidly reaches the ventral part of the tuberal hypothalamus. In conclusion, our study provides novel and valuable information about the pattern and mechanisms behind GH transport into the mouse brain.

Human bacterial infections significantly contribute to the increase in healthcare-related burdens. This scenario drives the study of novel techniques for the early and precise diagnosis of infectious processes. Some alternatives include Nuclear Medicine- and Molecular Imaging-based strategies. However, radiopharmaceuticals that are available for routine assessments are not specific to differentiating infectious from aseptic inflammatory processes. In this context, [⁶⁸Ga]Ga-DOTA-Ubiquicidin_29-41 was synthesized using an automated module and radiochemical; in vivo and in vitro studies were performed. The radiopharmaceutical remained stable in saline (up to 180 min) and in rodent serum (up to 120 min) with radiochemical purities > 99 and 95%, respectively. Partition coefficient and serum protein binding at 60 min were determined (−3.63 ± 0.17 and 44.06 ± 1.88%, respectively). Ex vivo biodistribution, as well as in vivo microPET/CT images in mice, showed rapid blood clearance with renal excretion and reduced uptake in other organs in Staphylococcus aureus-infected animals. Higher uptake was observed in the target as compared to the non-target tissue (p < 0.0001) at 60 min post administration. The presented in-human clinical case demonstrates uptake of the radiopharmaceutical by Staphyloccocus aureus bacteria. These results indicate the potential of [⁶⁸Ga]Ga-DOTA-Ubiquicidin_29-41 as a radiopharmaceutical that can be obtained in a hospital radiopharmacy for the diagnosis of infectious processes using PET/CT.

This study employed molecular imaging to evaluate MCP (PectaSol-C, modified citrus pectin, a complex polysaccharide with antitumor potential) absorption and pharmacokinetics following oral and intravenous (IV) administration. MCP was radiolabeled with technetium-99m (^99mTc) ([^99mTc]MCP), allowing precise in vivo tracking. Imaging and biodistribution analyzes revealed low tumor uptake of IV [^99mTc]MCP, with predominant renal and hepatobiliary clearance. Within tumors, MCP was detected at low levels and did not bind to viable cells. Consistent with these findings, IV administration produced only modest antitumor effects (∼50% tumor growth reduction) in SKOV-3 (ovarian), MKN45 (gastric), and 4T1 (breast) grafts, whereas oral administration was ineffective due to extremely poor absorption (bioavailability <0.01%). Notably, faster clearance of [^99mTc]MCP in galectin-3 (Gal-3) knockout mice suggests a role for Gal-3 in systemic retention or an indirect contribution to antitumor activity. These findings provide new insights into MCP pharmacological profile, highlight the limitations of oral delivery, and underscore the need for improved delivery strategies to enhance the therapeutic potential of pectin-based cancer treatments.

Background: Acquired resistance and adverse effects are some of the challenges faced by thousands of Luminal A breast cancer patients under tamoxifen (TMX) treatment. Some authors associate the overexpression of HOXB7 with TMX resistance in this molecular subtype, and the knockdown of this gene could be an effective strategy to regain TMX sensitivity. Therefore, we used calcium phosphate hybrid nanoparticles (HNP) for the delivery of short interfering RNA molecule (siRNA) complementary to the HOXB7 gene and evaluated the RNA interference (RNAi) effects associated with TMX treatment in breast cancer in vivo. Methods: HNP were prepared by the self-assembly of a methoxy-poly (ethylene glycol)-block-poly (L-glutamic acid) copolymer (PEG-pGlu) and the coprecipitation of CaPO₄ to incorporate siRNA. The in vitro cell viability and migration were evaluated prior to in vivo experiments. Further, animals bearing early-stage and advanced Luminal A breast cancer were treated with HNP-siHOXB7, HNP-siHOXB7 + TMX, and TMX. Antitumoral activity and gene expression were evaluated following histopathological, hematological, and biochemical analysis. Results: The HNP were efficient in delivering the siRNA in vitro and in vivo, whilst HOXB7 silencing associated with TMX administration promoted controlled tumor growth, as well as a higher survival rate and reduction in immuno- and hepatotoxicity. Conclusions: Therefore, our findings suggest that HOXB7 can be an interesting molecular target for Luminal A breast cancer, especially associated with hormone therapy, aiming for adverse effect mitigation and higher therapeutic efficacy.

Prostate cancer, a leading cause of morbidity and mortality among men, requires safer and more effective therapeutic approaches. Nanotechnology has emerged as a promising strategy to optimize therapeutic agent distribution and reduce adverse effects of conventional treatments. This study presents the development and evaluation of radioactive gold nanoparticles (198AuNPs) coated with gum arabic (GA) for prostate cancer treatment. While BSA-coated nanoparticles have been previously studied by our group, demonstrating therapeutic effectiveness, stability, and biocompatibility, the current work focuses exclusively on the GA formulation, which features a distinct synthesis protocol. In vitro and in vivo assays with 198AuNPs-GA demonstrated good stability, low toxicity in nontumor cells, tumor retention, and reduced tumor growth in animal models. References to BSA are included only for contextual comparison. These findings support the feasibility of gum arabic-coated 198AuNPs and offer new insights for enhancing future clinical strategies.