RESUMO
Injectable colloidal solutions of lanthanide oxides (nanoparticles between 10 and 100 nm in size) have demonstrated high biocompatibility and no toxicity when the nanoparticulate units are functionalized with specific biomolecules that molecularly target various proteins in the tumor microenvironment. Among the proteins successfully targeted by functionalized lanthanide nanoparticles are folic receptors, fibroblast activation protein (FAP), gastrin-releasing peptide receptor (GRP-R), prostate-specific membrane antigen (PSMA), and integrins associated with tumor neovasculature. Lutetium, samarium, europium, holmium, and terbium, either as lanthanide oxide nanoparticles or as nanoparticles doped with lanthanide ions, have demonstrated their theranostic potential through their ability to generate molecular images by magnetic resonance, nuclear, optical, or computed tomography imaging. Likewise, photodynamic therapy, targeted radiotherapy (neutron-activated nanoparticles), drug delivery guidance, and image-guided tumor therapy are some examples of their potential therapeutic applications. This review provides an overview of cancer theranostics based on lanthanide nanoparticles coated with specific peptides, ligands, and proteins targeting the tumor microenvironment.
RESUMO
Actinium-225 and other alpha-particle-emitting radionuclides have shown high potential for cancer treatment. Reconstituted high-density lipoproteins (rHDL) specifically recognize the scavenger receptor B type I (SR-BI) overexpressed in several types of cancer cells. Furthermore, after rHDL-SR-BI recognition, the rHDL content is injected into the cell cytoplasm. This research aimed to prepare a targeted 225Ac-delivering nanosystem by encapsulating the radionuclide into rHDL nanoparticles. The synthesis of rHDL was performed in two steps using the microfluidic synthesis method for the subsequent encapsulation of 225Ac, previously complexed to a lipophilic molecule (225Ac-DOTA-benzene-p-SCN, CLog P = 3.42). The nanosystem (13 nm particle size) showed a radiochemical purity higher than 99% and stability in human serum. In vitro studies in HEP-G2 and PC-3 cancer cells (SR-BI positive) demonstrated that 225Ac was successfully internalized into the cytoplasm of cells, delivering high radiation doses to cell nuclei (107 Gy to PC-3 and 161 Gy to HEP-G2 nuclei at 24 h), resulting in a significant decrease in cell viability down to 3.22 ± 0.72% for the PC-3 and to 1.79 ± 0.23% for HEP-G2 at 192 h after 225Ac-rHDL treatment. After intratumoral 225Ac-rHDL administration in mice bearing HEP-G2 tumors, the biokinetic profile showed significant retention of radioactivity in the tumor masses (90.16 ± 2.52% of the injected activity), which generated ablative radiation doses (649 Gy/MBq). The results demonstrated adequate properties of rHDL as a stable carrier for selective deposition of 225Ac within cancer cells overexpressing SR-BI. The results obtained in this research justify further preclinical studies, designed to evaluate the therapeutic efficacy of the 225Ac-rHDL system for targeted alpha-particle therapy of tumors that overexpress the SR-BI receptor.
Assuntos
Nanopartículas , Neoplasias , Partículas alfa/uso terapêutico , Animais , Lipoproteínas HDL/química , Camundongos , Nanopartículas/química , Neoplasias/tratamento farmacológico , Neoplasias/radioterapia , Receptores DepuradoresRESUMO
Fibroblast activation protein (FAP) is expressed in the microenvironment of most human epithelial tumors. 68Ga-labeled FAP inhibitors based on the cyanopyrrolidine structure (FAPI) are currently used for the detection of the tumor microenvironment by PET imaging. This research aimed to design, synthesize and preclinically evaluate a new FAP inhibitor radiopharmaceutical based on the 99mTc-((R)-1-((6-hydrazinylnicotinoyl)-D-alanyl) pyrrolidin-2-yl) boronic acid (99mTc-iFAP) structure for SPECT imaging. Molecular docking for affinity calculations was performed using the AutoDock software. The chemical synthesis was based on a series of coupling reactions of 6-hidrazinylnicotinic acid (HYNIC) and D-alanine to a boronic acid derivative. The iFAP was prepared as a lyophilized formulation based on EDDA/SnCl2 for labeling with 99mTc. The radiochemical purity (R.P.) was verified via ITLC-SG and reversed-phase radio-HPLC. The stability in human serum was evaluated by size-exclusion HPLC. In vitro cell uptake was assessed using N30 stromal endometrial cells (FAP positive) and human fibroblasts (FAP negative). Biodistribution and tumor uptake were determined in Hep-G2 tumor-bearing nude mice, from which images were acquired using a micro-SPECT/CT. The iFAP ligand (Ki = 0.536 nm, AutoDock affinity), characterized by UV-Vis, FT-IR, 1H-NMR and UPLC-mass spectroscopies, was synthesized with a chemical purity of 92%. The 99mTc-iFAP was obtained with a R.P. >98%. In vitro and in vivo studies indicated high radiotracer stability in human serum (>95% at 24 h), specific recognition for FAP, high tumor uptake (7.05 ± 1.13% ID/g at 30 min) and fast kidney elimination. The results found in this research justify additional dosimetric and clinical studies to establish the sensitivity and specificity of the 99mTc-iFAP.
Assuntos
Endopeptidases/metabolismo , Neoplasias Hepáticas Experimentais , Proteínas de Membrana/metabolismo , Proteínas de Neoplasias/metabolismo , Compostos de Organotecnécio , Compostos Radiofarmacêuticos , Tomografia Computadorizada com Tomografia Computadorizada de Emissão de Fóton Único , Tecnécio , Animais , Células Hep G2 , Humanos , Neoplasias Hepáticas Experimentais/diagnóstico por imagem , Neoplasias Hepáticas Experimentais/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Compostos de Organotecnécio/química , Compostos de Organotecnécio/farmacocinética , Compostos de Organotecnécio/farmacologia , Compostos Radiofarmacêuticos/química , Compostos Radiofarmacêuticos/farmacocinética , Compostos Radiofarmacêuticos/farmacologia , Tecnécio/química , Tecnécio/farmacocinética , Tecnécio/farmacologiaRESUMO
Polymeric nanoparticles encompass micelles and dendrimers. They are used for improving or controlling the action of the loaded therapy or imaging agent, including radionuclides. Some radionuclides possess properties appropriate for simultaneous imaging and therapy of a disease and are therefore called theranostic. The diversity in core materials and surface modification, as well as radiolabeling strategies, offers multiples possibilities for preparing polymeric nanoparticles using radionuclides. The present review describes different strategies in the preparation of such nanoparticles and their applications in nuclear nanomedicine.
Assuntos
Dendrímeros/química , Sistemas de Liberação de Medicamentos , Micelas , Radioisótopos/uso terapêutico , Nanomedicina Teranóstica , Animais , Humanos , Nanopartículas/químicaRESUMO
Protein interactions are the basis for the biological functioning of human beings. However, many of these interactions are also responsible for diseases, including cancer. Synthetic inhibitors of protein interactions based on small molecules are widely investigated in medicinal chemistry. The development of radiolabeled protein-inhibitor peptides for molecular imaging and targeted therapy with quickstep towards clinical translation is an interesting and active research field in the radiopharmaceutical sciences. In this article, recent achievements concerning the design, translational research and theranostic applications of structurally-modified small radiopeptides, such as prostate-specific membrane antigen (PSMA) inhibitors, fibroblast activation protein (FAP) inhibitors and antagonists of chemokine-4 receptor ligands (CXCR-4-L), with high affinity for cancer-associated target proteins, are reviewed and discussed.
Assuntos
Imagem Molecular , Neoplasias , Peptídeos/química , Compostos Radiofarmacêuticos/química , Humanos , Neoplasias/diagnóstico por imagem , Neoplasias/tratamento farmacológico , Medicina de PrecisãoRESUMO
The gastrin-releasing peptide receptor (GRPr) is overexpressed in >75% of breast cancers. 177Lu-Bombesin (177Lu-BN) has demonstrated the ability to target GRPr and facilitate efficient delivery of therapeutic radiation doses to malignant cells. Poly(d,llactidecoglycolide) acid (PLGA) nanoparticles can work as smart drug controlled-release systems activated through pH changes. Considering that paclitaxel (PTX) is a first-line drug for cancer treatment, this work aimed to synthesize and chemically characterize a novel polymeric PTX-loaded nanosystem with grafted 177Lu-BN and to evaluate its performance as a targeted controlled-release nanomedicine for concomitant radiotherapy and chemotherapy of breast cancer. PLGA(PTX) nanoparticles were synthesized using the single emulsification-solvent evaporation method with PVA as a stabilizer in the presence of PTX. Thereafter, the activation of PLGA carboxylic groups for BN attachment through the Lys1-amine group was performed. Results of the chemical characterization by FT-IR, DLS, HPLC and SEM/TEM demonstrated the successful synthesis of BN-PLGA(PTX) with a hydrodynamic diameter of 163.54⯱â¯33.25â¯nm. The entrapment efficiency of paclitaxel was 92.8⯱â¯3.6%. The nanosystem showed an adequate controlled release of the anticancer drug, which increased significantly due to the pH change from neutral (pHâ¯=â¯7.4) to acidic conditions (pHâ¯=â¯5.3). After labeling with 177Lu and purification by ultrafiltration, 177Lu-BN-PLGA(PTX) was obtained with a radiochemical purity of 99⯱â¯1%. In vitro and in vivo studies using MDA-MB-231 breast cancer cells (GRPr-positive) demonstrated a 177Lu-BN-PLGA(PTX) specific uptake and a significantly higher cytotoxic effect for the radiolabeled nanosystem than the unlabeled BN-PLGA(PTX) nanoparticles. Using a pulmonary micrometastasis MDA-MB-231 model, the added value of 177Lu-BN-PLGA(PTX) for tumor imaging was confirmed. The 177Lu-BN-PLGA(PTX) nanomedicine is suitable as a targeted paclitaxel delivery system with concomitant radiotherapeutic effect for the treatment of GRPr-positive breast cancer.
Assuntos
Bombesina/química , Neoplasias da Mama/tratamento farmacológico , Lutécio/química , Nanomedicina , Paclitaxel/uso terapêutico , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Radioisótopos/química , Animais , Neoplasias da Mama/patologia , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Núcleo Celular/efeitos da radiação , Sobrevivência Celular/efeitos dos fármacos , Preparações de Ação Retardada/farmacologia , Preparações de Ação Retardada/uso terapêutico , Liberação Controlada de Fármacos , Endocitose , Feminino , Humanos , Camundongos , Nanopartículas/química , Nanopartículas/ultraestrutura , Paclitaxel/química , Paclitaxel/farmacologia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Tomografia Computadorizada de Emissão de Fóton ÚnicoRESUMO
About 90% of insulinomas are benign and 5%-15% are malignant. Benign insulinomas express the glucagon-like peptide-1 receptor (GLP-1R) and low levels of somatostatin receptors (SSTR), while malignant insulinomas over-express SSTR or GLP-1R in low levels. A kit for the preparation of Lys(27)((99m)Tc-EDDA/HYNIC)-Exendin(9-39)/(99m)Tc-EDDA/HYNIC-Tyr(3)Octreotide was formulated to detect 100% of insulinomas. The formulation showed radiochemical purity of 97±1%, high stability in human serum, and GLP-1R and SSTR affinity. The biodistribution and imaging studies demonstrated properties suitable for its use as a target-specific agent for the simultaneous molecular imaging of GRP-1R- and/or SSTR-positive tumors.
Assuntos
Ácido Edético/análogos & derivados , Insulinoma/diagnóstico por imagem , Compostos de Organotecnécio/química , Compostos de Organotecnécio/farmacocinética , Neoplasias Pancreáticas/diagnóstico por imagem , Compostos Radiofarmacêuticos/química , Compostos Radiofarmacêuticos/farmacocinética , Animais , Ácido Edético/química , Liofilização , Humanos , Insulinoma/patologia , Masculino , Camundongos , Camundongos Nus , Neoplasias Pancreáticas/patologia , Radioquímica , Cintilografia , Ratos , Distribuição Tecidual , Células Tumorais CultivadasRESUMO
Infectious diseases remain a major health problem and cause of death worldwide. A variety of radiopharmaceuticals are used for the imaging of infections and inflammation in the practice of nuclear medicine. Long-term clinical use has shown that the majority of radiolabeled probes cannot distinguish between inflammation and infection. Gallium-67-citrate binds to bacteria, but also to proteins accumulating at both sterile inflammation and bacterial infection sites. Other agents are used to interact with receptors or domains on circulating and infiltrating leukocytes or to label them directly. However, these probes cannot distinguish between infection and inflammation because they are not specific to infectious micro-organisms. This review examines the recent developments and applications of radiolabeled specific agents, such as antiviral drugs, antifungal, antibiotics and antimicrobial peptides, to visualize infectious foci by targeting viruses, fungi or bacteria.
Assuntos
Sistemas de Liberação de Medicamentos , Desenho de Fármacos , Compostos Radiofarmacêuticos , Animais , Antibacterianos/administração & dosagem , Antifúngicos/administração & dosagem , Antivirais/administração & dosagem , Infecções Bacterianas/diagnóstico por imagem , Infecções Bacterianas/microbiologia , Humanos , Inflamação/diagnóstico por imagem , Micoses/diagnóstico por imagem , Micoses/microbiologia , Cintilografia , Viroses/diagnóstico por imagem , Viroses/microbiologiaRESUMO
99mTc-UBI 29-41 is an antimicrobial peptide fragment that directly radiolabeled with 99mTc shows high in vitro and in vivo stability, rapid background clearance, minimal accumulation in non-target tissues and rapid detection of infection sites. Molecular mechanics (MM) calculation has been an essential tool in explaining experimental results associated with molecular recognition and stability. This work is an attempt to explain the 99mTc-UBI 29-41 specificity for bacteria and to understand from a structural point of view, the experimental results indicative of a molecular recognition and stability not well favored for two other cationic peptides (99mTc-Tat-1-Scr and 99mTc-Tat-2-Scr ) used as control. Structures of 99mTc-UBI, 99mTc-Tat-1-Scr, 99mTc-Tat-2-Scr and of the corresponding free cationic peptides were built and the optimized structures, in the best stable configurations, were calculated by a MM procedure. In order to correlate the calculated and experimental results, in vitro stability tests with cysteine challenge and stability to dilution in human serum and in saline solution, were performed for the three labeled cationic peptides. The three complexes can be represented by the general formula [Tc(V)(O)(H2O)2(Lysn=1,2-Argn=0,1-peptide)]10+,11+. The potential energies were 104.5, 95.6 and 90.8 kcal/mol for 99mTc-Tat-1-Scr, 99mTc-Tat-2-Scr and 99mTc-UBI 29-41, respectively. Experimental and calculated results were in good agreement. It is thus possible to predict and explain that in similar solution media 99mTc-Tat-2-Scr would be more stable than 99mTc-Tat-1-Scr and why 99mTc-UBI shows the highest stability. In conclusion, the in vitro specific binding to bacteria and the accumulation at infection sites in humans of 99mTc-labeled UBI could be the result of its high thermodynamic stability, selectivity and stereospecificity.
Assuntos
Modelos Moleculares , Compostos de Organotecnécio/sangue , Compostos de Organotecnécio/química , Fragmentos de Peptídeos/sangue , Fragmentos de Peptídeos/química , Infecções Bacterianas/diagnóstico por imagem , Simulação por Computador , Estabilidade de Medicamentos , Humanos , Ligação Proteica , Conformação Proteica , Cintilografia , Compostos Radiofarmacêuticos/sangue , Compostos Radiofarmacêuticos/química , Relação Estrutura-AtividadeRESUMO
Antimicrobial peptides have been proposed as new agents to distinguish between bacterial infections and sterile inflammatory processes. (99m)Tc-UBI labeled by a direct method has shown high in vitro and in vivo stability, specific uptake at the site of infection, rapid background clearance, minimal accumulation in non-target tissues and rapid detection of infection sites in mice. The aim of this study was to establish a (99m)Tc-UBI biokinetic model and evaluate its feasibility as an infection imaging agent in humans. Whole-body images from 6 children with suspected bone infection were acquired at 1, 30, 120, 240 min and 24 h after (99m)Tc-UBI administration. Regions of interest (ROIs) were drawn around source organs (heart, liver, kidneys and bladder) on each time frame. The same set of ROIs was used for all 6 scans and the cpm of each ROI were converted to activity using the conjugate view counting method. Counts were corrected by physical decay and by the background correction factor derived from preclinical phantom studies. The image sequence was used to extrapolate (99m)Tc-UBI time-activity curves in each organ and calculate the cumulated activity (A). Urine samples were used to obtain the cumulative percent of injected activity (% I.A.) versus time renal elimination. The absorbed dose in organs was evaluated according to the general equation described in the MIRD formalism. In addition, (67)Ga-citrate images were obtained from all the patients and used as a control. Biokinetic data showed a fast blood clearance with a mean residence time of 0.52 h. Approximately 85% of the injected activity was eliminated by renal clearance 24 h after (99m)Tc-UBI administration. Images showed minimal accumulation in non-target tissues with an average target/non-target ratio of 2.18 +/- 0.74 in positive lesions at 2 h. All infection positive(99m)Tc-UBI images were in agreement with those obtained with (67)Ga-citrate. The mean radiation absorbed dose calculated was 0.13 mGy/MBq for kidneys and the effective dose was 4.34 x 10(-3)mSv/MBq.
Assuntos
Interpretação de Imagem Assistida por Computador/métodos , Modelos Biológicos , Osteíte/diagnóstico por imagem , Osteíte/metabolismo , Proteínas Ribossômicas/farmacocinética , Adolescente , Criança , Pré-Escolar , Citratos/farmacocinética , Simulação por Computador , Estudos de Viabilidade , Feminino , Gálio/farmacocinética , Humanos , Cinética , Masculino , Taxa de Depuração Metabólica , Especificidade de Órgãos , Fragmentos de Peptídeos/farmacocinética , Imagens de Fantasmas , Compostos Radiofarmacêuticos/farmacocinética , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Distribuição Tecidual , Tomografia Computadorizada de Emissão de Fóton Único/instrumentação , Tomografia Computadorizada de Emissão de Fóton Único/métodos , Contagem Corporal TotalRESUMO
Technetium-99m labeled ubiquicidin peptide 29-41 ((99m)Tc-UBI) is a cationic human antimicrobial peptide fragment that has been shown to bind bacteria in vitro and accumulates at sites of infection in experimental animals. To help determine if (99m)Tc-UBI is bound to the bacterial cell envelope by a simple nonspecific electrostatic interaction, a comparative study of the in vitro binding of (99m)Tc-UBI and two different (99m)Tc labeled cationic peptides ((99m)Tc-Tat-1-Scr and (99m)Tc-Tat-2-Scr) to bacteria and to two tumor cell line (LS174T and ACHN) was performed. The in vivo specificity of (99m)Tc-UBI for infection in mice was also evaluated using dual labels in the same animal and comparing the target/non-target ratio for (67)Ga-citrate and (99m)Tc-UBI at sites of induced infection and sterile inflammation. Under conditions of this study, the in vitro binding of (99m)Tc-UBI, (99m)Tc-Tat-1-Scr and (99m)Tc-Tat-2-Scr to S. aureus was 35, 78 and 87% respectively. While the binding of (99m)Tc-Tat-1-Scr and (99m)Tc-Tat-2-Scr was 37 and 33% to colon tumor cells (LS174T) and 39 and 41% to renal tumor cells (ACHN) respectively, the binding of (99m)Tc-UBI to both cell types was much lower at less than 4%. In vivo studies revealed that there is a significant difference (p < 0.05) in the radioactive accumulation of (99m)Tc-UBI between the sites of infection and inflammation compared to (67)Ga-citrate. Thus, (99m)Tc-UBI showed an average infection/inflammation ratio of 2.08 +/- 0.49 compared to 1.14 +/- 0.45 for (67)Ga-citrate. In conclusion, the in vitro and in vivo results provide evidence that a specific mechanism is responsible of the (99m)Tc-UBI bacterial intracellular accumulation.
Assuntos
Carcinoma de Células Renais/diagnóstico por imagem , Carcinoma de Células Renais/metabolismo , Neoplasias do Colo/diagnóstico por imagem , Neoplasias do Colo/metabolismo , Compostos de Organotecnécio/farmacocinética , Fragmentos de Peptídeos/farmacocinética , Infecções Estafilocócicas/diagnóstico por imagem , Infecções Estafilocócicas/metabolismo , Staphylococcus aureus/metabolismo , Animais , Linhagem Celular Tumoral , Citratos/farmacocinética , Gálio/farmacocinética , Humanos , Neoplasias Renais/diagnóstico por imagem , Neoplasias Renais/metabolismo , Camundongos , Cintilografia , Compostos Radiofarmacêuticos/farmacocinética , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Staphylococcus aureus/isolamento & purificaçãoRESUMO
The aim of this study was to help establish if ubiquicidin peptide 29-41 fragment (UBI) contains a specific site for 99mTc labeling by a new direct method under alkaline conditions. Since this peptide does not have cysteine residues, it is possible that neighboring arginine and lysine in the peptide amino acid sequence (Thr-Gly-Arg-Ala-Lys-Arg-Arg-Met-Gln-Tyr-Asn-Arg-Arg) could be a specific coordination site to form a stable 99mTc-UBI complex. Following direct labeling, the in vitro stability of 99mTc-UBI was compared to UBI radiolabeled by one indirect method using HYNIC/tricine and HYNIC/tricine/EDDA. Radiochemical purity of 99mTc-UBI averaged 97% compared to 88% for 99mTc-HYNIC-UBI/tricine and 98% for 99mTc-HYNIC-UBI/tricine/EDDA. Both 99mTc-HYNIC-UBI (tricine or EDDA) and 99mTc-UBI showed stability in human serum and solutions of cysteine. 99mTc-UBI radiochemical purity 24 h after dilution in 0.9% NaCl was greater than 90% at pH 9 and greater than 95% at pH 6.5. Under one set of experimental conditions, in vitro binding to bacteria of 99mTc-UBI was 35% and identical to that of 99mTc-HYNIC-UBI/tricine and 99mTc-HYNIC-UBI/tricine/EDDA at 32% and 31% respectively. The biodistribution of 99mTc-UBI in mice showed a rapid renal clearance. To help identify the site(s) of 99mTc binding following direct labeling, molecular mechanics and quantum-mechanical calculations were performed which showed that the amine groups of Arg(7) and Lys are the most probable site. The calculations show that these groups can form a square pyramid with two water molecules for the Tc cation (dxysp(3)). It will be necessary to isolate and characterize the 99Tc(V)(O)-UBI.(H2O)n complex to confirm these results.
Assuntos
Arginina/química , Marcação por Isótopo/métodos , Lisina/química , Proteínas Ribossômicas/química , Proteínas Ribossômicas/farmacocinética , Staphylococcus/metabolismo , Tecnécio/química , Tecnécio/farmacocinética , Animais , Sítios de Ligação , Simulação por Computador , Estabilidade de Medicamentos , Hidrazinas/química , Masculino , Taxa de Depuração Metabólica , Camundongos , Camundongos Endogâmicos BALB C , Modelos Moleculares , Ácidos Nicotínicos/química , Especificidade de Órgãos , Ligação Proteica , Compostos Radiofarmacêuticos/síntese química , Compostos Radiofarmacêuticos/química , Compostos Radiofarmacêuticos/farmacocinética , Proteínas Ribossômicas/sangue , Relação Estrutura-Atividade , Tecnécio/sangue , Distribuição TecidualRESUMO
La dosis absorbida determina el riesgo/beneficio que recibe el paciente a quien se le administra un radiofármaco y se calcula con modelos biológicos y matemáticos. El biológico relaciona los datos experimentales de sangre y orina para obtener la actividad acumulada y el valor del tiempo de residencia promedio t. Con el modelo matemático MIRD, se obtiene, a partir de t, el cálculo de la dosis absorbida utilizando el programa de computación MIRDOSE3.En la Unidad de Radiofarmacia del Departamento de Medicina Nuclear del INCMNSZ se desarrollaron, caracterizaron y probaron en animales dos radiofármacos osteotrópicos originales: 99mTc-ABP y 188Re-ABP. Además, con el primero se obtuvieron valores radiofarmacocinéticos, en 10 sujetos normales, por medio de muestras seriadas de sangre y orina durante 24 h y por medio de regiones de interés (RDI) trazadas sobre gammagramas óseos seriados. Los valores obtenidos para por ciento de eliminación en orina y por ciento de captación en hueso se utilizaron para el cálculo de la dosis absorbida con 99mTc-ABP y para el cálculo extrapolado con 188Re-ABP como fundamento para calcular la actividad a usar en el tratamiento terapéutico.El 99mTc-ABP se eliminó por orina para mujeres 63.2 ñ 7.3 por ciento de la actividad administrada en 24 h y para hombres 70 ñ 11 por ciento. La actividad remanente en hueso fue para mujeres 36.8 ñ 7.3 por ciento y para hombres 30 ñ 11 por ciento. Se delimitaron RDIs sobre las imágenes gammagráficas y al integrar las cpm/pixel/RDI sobre riñón en función del tiempo se obtuvo el tiempo de residencia t = 0.52 h. Con la ecuación =1.443 (T½) A0 se calculó la actividad acumulada en hueso 2358 ñ 469 MBq h en mujeres y 1923 ñ 707 MBq h para hombres; t = 3.19 ñ 0.63 h (mujeres) y 2.6 ñ 0.95 h en hueso para los hombres. La dosis absorbida para cuerpo entero en mujeres fue 0.0020 ñ 0.0004 mGy/MBq y 0.0013 ñ 0.0005 mGy/MBq para los hombres. La dosis absorbida en médula ósea fue 0.0063 ñ 0.0013 mGy/MBq en las mujeres y 0.0041 ñ 0.0015 mGy/MBq en hombres. El 188Re es un emisor de radiaciones beta negativa y considerando que el 188Re-ABP se comporta igual al radiofármaco de tecnecio-99m, la dosis efectiva a las mujeres sería 0.0936 mSv/MBq y 0.0608 mSv/MBq para los hombres. Estas características y las características radionuclídicas del 188Re serían las apropiadas para utilizar 188Re-ABP como un buen agente paliativo del dolor producido por las metástasis óseas.
Assuntos
Humanos , Masculino , Feminino , Adulto , Planejamento da Radioterapia Assistida por Computador/métodos , Compostos Radiofarmacêuticos/farmacocinética , Radiometria , Dosimetria , Medicina NuclearRESUMO
Background. Technetium-99m-mercaptoacetyltriglycine (99-mTc-MAG3) is a radiopharmaceutical for tubular function and can be prepared with 99-mtechnetium and the ligand Bz-MAG3 (Instituto Nacional de Investigaciones Nucleares, Mexico City). No radiopharmacokinetic parameters have been found for the healty adult Mexican population with 99mTc-MAG3, prepared with the nationally produced or imported Bz-MAG3 kit. Methods. The radiopharmacokinetic parametrs and the clearance of 99mTc-Mag3 in seven healthy Mexican volunteers were determined by the single-and multi-sample methods. Computer programs were used for the calculations. Results. Using several plasma samples from 0.43 min and the BIEXP program, it was show that 99mTc-MAG3 follows a two-compartment model of distribution, with an apparent volumen in the central compartment Vdcc = 6.7 + 1.0 1, T½Ó = 0.07 + 0.02 h-1, T½ ß = 0.49 + 0.15 h-1, mean residence time MRT = 0.60 + 0.17 h and clearance = 208 57 (ml/min)/1.73 m². In comparison, the clearance value with a single sample drawn 43 min post-injection and calculated with Tauxe's formula was 193 ñ 59 (ml/min)/m². Conclusions. The 15 ml difference between the two methods is neither statistically different (p= 0.11) nor important for routine clinical studies. The single-sample method is recommendad because it is reliable and can be done at the same time that dynamic renal scan is aquiered. Estimated absorbed radiation dose was calvulated for several organs
Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Compostos Radiofarmacêuticos , Tecnécio Tc 99m Mertiatida/farmacocinética , Doses de Radiação , Radiometria , Tecnécio Tc 99m Mertiatida/sangue , Testes de Função Renal , Distribuição TecidualRESUMO
Objetivo. Comparar la calidad de las imágenes de gammagrafía ósea obtenidas con un radiofármaco nuevo, el 99mTc-ABP, con aquéllas obtenidas con el 99mTc-MDP. Material y métodos. Fue un estudio comparativo en un mismo sujeto. Se estudiaron 9 voluntarios sanos (5 mujeres y 4 hombres) de 23 a 39 años de edad. A todos se les inyectaron 740 MBq de los radiofármacos Tc-ABP y Tc-MDP con un intervalo de 72 horas entre uno y otro. Dos horas después de cada inyección se les realizó un gammagrama óseo de cuerpo entero con una cámara de centello MultiSpect 2 y se determinaron los parámetros radiofarmacocinéticos. Tres médicos nucleares evaluaron por separado la calidad de las imágenes mediante el trazado de regiones de interés (RDI) sobre vértebras, costillas, esternón, fémur, articulaciones y cráneo. Se obtuvieron relaciones hueso/músculo con RDI sobre diferentes huesos. Los resultados se compararon etadísticamente con las pruebas de kappa y de Wilcoxon. Resultados. La concordancia sobre la calidad de las imágenes de los dos radiofármacos por los tres observadores fue moderada (kappa 0.4). La relación fémur/músculo mostró una distribución normal y no manifestó diferencias significativas entre radiofármacos. Conclusiones. La calidad de las imágenes con ambas preparaciones fue similar. Recomendamos utilizar al 99mTc-ABP en la gammagrafía ósea debido a la menor exposición a radiación del paciente
Assuntos
Humanos , Masculino , Feminino , Adulto , Alendronato , Osso e Ossos , Compostos de Organotecnécio , Compostos de Organotecnécio/farmacocinética , Medronato de Tecnécio Tc 99m , Medronato de Tecnécio Tc 99m/farmacocinéticaRESUMO
The purpose of this paper is to report the preparation of a new technetium-99m-radiopharmaceutical for bone scanning. The chelating agent for99mTc is a new bisphosphonate, alendronate, 4-amino-1-hydroxy-butylidene-1,1-bisphosphonate (ABP) used as a treatment for osteoporosis. ABP, because of its amino group, seems to be better suited to form a strong and stable complex with technetium-99m and therefore might be better than 99mTc-etidronate (HEDP) or 99mTc-medronate (MDP) for bone scanning. A sterile dry kit containing APB, a reducing agent and a stabilizer was prepared. The parameters studied were molar concentrations, pH, shelf life, labeling efficiency and radiochemical purity. the oven dried sterile kit was formulated with 5 mg ABP, 0.25 mg stannous fluoride and 0.025 mg gentisic acid at pH2.5-3.5. The labeling efficiency with 20 - 1500 MBq of pertechnetate (99mTcO4-) was over 95 percent at room temperature and was stable for 5 h. Technetium-99m-alendronate was tested in two rabbits and it proved to be a promising new radiopharmaceutical for bone scanning. Work is underway to study underway to study 99m-Tc-ABP biodistribution in a statistically significant number of laboratory animals and, later on, to determine radiopharmacokinetic parameters in normal volunteers