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Background: Nanotechnology has revolutionized medicine, especially in oncological treatments. Gold nanoparticles (AuNPs) stand out as an innovative alternative due to their biocompatibility, potential for surface modification, and effectiveness in radiotherapeutic techniques. Given that prostate cancer ranks as one of the leading malignancies among men, there's a pressing need to investigate new therapeutic approaches. Methods: AuNPs coated with bovine serum albumin (BSA) were synthesized and their cytotoxicity was assessed against prostate tumor cell lines (LNCaP and PC-3), healthy prostate cells (RWPE-1), and endothelial control cells (HUVEC) using the MTS/PMS assay. For in vivo studies, BALB/C Nude mice were employed to gauge the therapeutic efficacy, biodistribution, and hematological implications post-treatment with BSA-coated AuNPs. Results: The BSA-coated AuNPs exhibited cytotoxic potential against PC-3 and LNCaP lines, while interactions with RWPE-1 and HUVEC remain subjects for further scrutiny. Within animal models, a diverse therapeutic response was observed, with certain instances indicating complete tumor regression. Biodistribution data emphasized the nanoparticles' affinity towards particular organs, and the majority of hematological indicators aligned with normative standards. Conclusions: BSA-coated AuNPs manifest substantial promise as therapeutic tools in treating prostate cancer. The present research not only accentuates the nanoparticles' efficacy but also stresses the imperative of optimization to ascertain both selectivity and safety. Such findings illuminate a promising trajectory for avant-garde therapeutic modalities, holding substantial implications for public health advancements.
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Nanopartículas del Metal , Neoplasias de la Próstata , Masculino , Animales , Ratones , Humanos , Oro/farmacología , Próstata/metabolismo , Albúmina Sérica Bovina/metabolismo , Distribución Tisular , Ratones Desnudos , Nanopartículas del Metal/uso terapéutico , Ratones Endogámicos BALB C , Neoplasias de la Próstata/radioterapia , Neoplasias de la Próstata/metabolismo , RadioisótoposRESUMEN
INTRODUCTION: The aim of this work was to quantify the effects of injection volume at different technetium-99m specific radiotracer doses on its lymphatic movement in animal model. PROCEDURES: Effects of injection volume (50, 100 µl) at different doses (0.05, 0.135, 0.22 nmol) on popliteal node (PN) detection were studied in rats. The radiotracer under study was (99m)Technetium-cysteine-mannose-dextran conjugate (30 kDa). RESULTS: At 0.05 nmol dose, higher PN uptake was observed at 50 µl injection volume (2.6 fold increase). Conversely, at 0.135 nmol dose, an increase of radiotracer retention in PN was achieved at 100 µl volume, 78% higher than 50 µl. However, at 0.22 nmol dose, the injection volume changes did not influence on the PN uptake. Considering as suitable radiotracer performance: high PN uptake and extraction, better combinations were 0.05 nmol/50 µl, 0.135 nmol/100 µl, 0.22/50 µl. CONCLUSION: Suitable performances could be reached by proper combinations of dose, injection volume and concentration for a specific radiotracer used in sentinel lymph node detection.
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Cisteína/análogos & derivados , Dextranos/farmacocinética , Ganglios Linfáticos/metabolismo , Manosa/farmacocinética , Compuestos de Organotecnecio/farmacocinética , Radiofármacos/farmacocinética , Animales , Cisteína/administración & dosificación , Cisteína/farmacocinética , Dextranos/administración & dosificación , Femenino , Ganglios Linfáticos/diagnóstico por imagen , Manosa/administración & dosificación , Compuestos de Organotecnecio/administración & dosificación , Cintigrafía , Radiofármacos/administración & dosificación , Ratas , Ratas Wistar , Biopsia del Ganglio Linfático Centinela/métodos , Distribución TisularRESUMEN
BACKGROUND: Biological performance of radiotracers for sentinel node detection analyzed in the light of molecular design and dimension is not widely available. PURPOSE: To evaluate the effect of dextran molecular size and the presence of tissue-binding units (mannose) within the model of (99m)Tc-carbonyl conjugate for sentinel lymph node detection. MATERIAL AND METHODS: Four dextran conjugates with and without mannose in the chemical backbone were included. All polymers were radiolabeled using the precursor [(99m)Tc(OH(2))(3)(CO)(3)](+). Radiolabeling conditions targeted the best radiochemical purity and specific activity for each radiopharmaceutical, and partition coefficients were also defined. Lymphoscintigraphy and ex-vivo biodistribution in popliteal lymph node, liver and kidneys were performed in Wistar rats. The effects of molecular weight and mannose presence were assessed by a two-level factorial design. RESULTS: Radiochemical purity was indirectly related to molecular weight and presence of mannose in the polymer structure. All products were able to detect popliteal lymph node, however, uptake was strongly influenced by use of mannose (4-fold higher). Excretion was similarly modulated by differences in molecular weight. Mannose-enhanced lymph node uptake and higher molecule size in the range under study benefitted lymphoscintigraphic performance. CONCLUSION: Screening of radiopharmaceuticals for lymphoscintigraphy might improve with attention to the mentioned physico-chemical features of the molecule.
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Metástasis Linfática/diagnóstico por imagen , Radiofármacos , Biopsia del Ganglio Linfático Centinela , Análisis de Varianza , Animales , Cisteína , Dextranos , Femenino , Manosa , Cintigrafía , Ratas , Ratas Wistar , Sensibilidad y Especificidad , TecnecioRESUMEN
The objective of this study was the development of a statistical approach for radiolabeling optimization of cysteine-dextran conjugates with Tc-99m tricarbonyl core. This strategy has been applied to the labeling of 2-propylene-S-cysteine-dextran in the attempt to prepare a new class of tracers for sentinel lymph node detection, and can be extended to other radiopharmaceuticals for different targets. The statistical routine was based on three-level factorial design. Best labeling conditions were achieved. The specific activity reached was 5 MBq/µg.
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Cisteína/química , Dextranos/química , Compuestos de Organotecnecio/química , Cromatografía en Gel , Control de CalidadRESUMEN
INTRODUCTION: Particle size of colloids employed for sentinel lymph node (LN) detection is not well studied. This investigation aimed to correlate particle size and distribution of different products with LN uptake. METHODS: All agents (colloidal tin, dextran, phytate and colloidal rhenium sulfide) were labeled with (99m)Tc according to manufacturer's instructions. Sizing of particles was carried out on electron micrographs using Image Tool for Windows (Version 2.0). Biodistribution studies in main excretion organs as well as in popliteal LN were performed in male Wistar rats [30 and 90 min post injection (p.i.)]. The injected dose was 0.1 ml (37 MBq) in the footpad of the left posterior limb. Dynamic images (0-15 min p.i.) as well as static ones (30 and 90 min) were acquired in gamma camera. RESULTS: Popliteal LN was clearly reached by all products. Nevertheless, particle size remarkably influenced node uptake. Colloidal rhenium sulfide, with the smallest diameter (5.1 x 10(-3)+/-3.9 x 10(-3) microm), permitted the best result [2.72+/-0.64 percent injected dose (%ID) at 90 min]. Phytate displayed small particles (<15 microm) with favorable uptake (1.02+/-0.14%ID). Dextran (21.4+/-12.8 microm) and colloidal tin (39.0+/-8.3 microm) were less effective (0.55+/-0.14 and 0.06+/-0.03%ID respectively). Particle distribution also tended to influence results. When asymmetric, it was associated with biphasic uptake which increased over time; conversely, symmetric distribution (colloidal tin) was consistent with a constant pattern. CONCLUSION: The results are suggesting that particle size and symmetry may interfere with LN radiopharmaceutical uptake.