Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 252
Filtrar
1.
Cancer Biother Radiopharm ; 39(5): 337-348, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38215243

RESUMO

Aim: ChiTn, a mouse/human chimeric anti-Tn monoclonal antibody, was radiolabeled with iodine-131 (131I) and technetium-99m (99mTc) to assess its biodistribution and internalization in Tn-expressing (Tn+) and wild-type (Tn-) LL/2 lung cancer cells. Results: Selective accumulation and gradual internalization of ChiTn were observed in Tn+ cells. Biodistribution in mice with both Tn+ or Tn- lung tumors indicated that the uptake of radiolabeled ChiTn within tumors increased over time. Dual-labeling experiments with 99mTc and 131I showed different biodistribution patterns, with 99mTc exhibiting higher values in the liver, spleen, and kidneys, while 131I showed higher uptake in the thyroid and stomach. However, tumor uptake did not significantly differ between Tn+ and Tn- tumors. To improve tumor targeting, Losartan, an antihypertensive drug known to enhance tumor perfusion and drug delivery, was investigated. Biodistribution studies in Losartan-treated mice revealed significantly higher radiolabeled ChiTn uptake in Tn+ tumors. No significant changes were observed in the uptake of the control molecule IgG-HYNIC™99mTc. Conclusions: These findings demonstrate the enhanced tumor targeting of radiolabeled ChiTn in Losartan-treated mice with Tn-expressing lung tumors. They highlight the potential of ChiTn as a theranostic agent for cancer treatment and emphasize the importance of Losartan as an adjunctive treatment to improve tumor perfusion and drug delivery.


Assuntos
Anticorpos Monoclonais , Radioisótopos do Iodo , Losartan , Neoplasias Pulmonares , Animais , Camundongos , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/metabolismo , Losartan/farmacologia , Losartan/farmacocinética , Losartan/administração & dosagem , Distribuição Tecidual , Anticorpos Monoclonais/farmacologia , Anticorpos Monoclonais/farmacocinética , Tecnécio , Compostos Radiofarmacêuticos/farmacocinética , Compostos Radiofarmacêuticos/farmacologia , Linhagem Celular Tumoral , Feminino , Proteína Tumoral 1 Controlada por Tradução
2.
Int J Pharm ; 652: 123765, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38195032

RESUMO

Despite the successful use of the radiopharmaceutical radium-223 dichloride ([223Ra]RaCl2) for targeted alpha therapy of castration-resistant prostate cancer patients with bone metastases, some short-term side effects, such as diarrhea and vomiting, have been documented, causing patient discomfort. Hence, we prepared a nanosized micellar solution of [223Ra]RaCl2 and evaluated its biodistribution, pharmacokinetics, and induced biochemical changes in healthy mice up to 96 h after intraperitoneal administration as an alternative to overcome the previous limitations. In addition, we evaluated the bone specificity of micellar [223Ra]RaCl2 in patient-derived xenografts in the osteosarcoma model. The biodistribution studies revealed the high bone-targeting properties of the micellar [223Ra]RaCl2. Interestingly, the liver uptake remained significantly low (%ID/g = 0.1-0.02) from 24 to 96 h after administration. In addition, the micellar [223Ra]RaCl2 exhibited a significantly higher uptake in left (%ID/g = 0.85-0.23) and right (%ID/g = 0.76-0.24) kidneys than in small (%ID/g = 0.43-0.06) and large intestines (%ID/g = 0.24-0.09) over time, suggesting its excretion pathway is primarily through the kidneys into the urine, in contrast to the non-micellar [223Ra]RaCl2. The micellar [223Ra]RaCl2 also had low distribution volume (0.055 ± 0.003 L) and longer elimination half-life (28 ± 12 days). This nanosystem was unable to change the enzymatic activities of alanine aminotransferase, aspartate aminotransferase, gamma GT, glucose, and liquiform lipase in the treated mice. Finally, microscopic examination of the animals' osteosarcoma tumors treated with micellar [223Ra]RaCl2 indicated regression of the tumor, with large areas of necrosis. In contrast, in the control group, we observed tumor cellularity and cell anaplasia, mitotic figures and formation of neoplastic extracellular bone matrix, which are typical features of osteosarcoma. Therefore, our findings demonstrated the efficiency and safety of nanosized micellar formulations to minimize the gastrointestinal excretion pathway of the clinical radiopharmaceutical [223Ra]RaCl2, in addition to promoting regression of the osteosarcoma. Further studies must be performed to assess dose-response outcomes and organ/tissue dosimetry for clinical translation.


Assuntos
Neoplasias Ósseas , Osteossarcoma , Neoplasias de Próstata Resistentes à Castração , Humanos , Masculino , Animais , Camundongos , Compostos Radiofarmacêuticos/farmacocinética , Distribuição Tecidual , Eliminação Renal , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/radioterapia , Osteossarcoma/tratamento farmacológico , Neoplasias de Próstata Resistentes à Castração/patologia
3.
Molecules ; 27(1)2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-35011496

RESUMO

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/farmacologia
4.
Artigo em Inglês | MEDLINE | ID: mdl-34250393

RESUMO

PURPOSE: Many novel therapies for relapsed and refractory neuroblastoma require tumor tissue for genomic sequencing. We analyze our experience with image-guided biopsy in these patients, focusing on safety, yield, adequacy for next-generation sequencing (NGS), and correlation of tumor cell percent (TC%) with quantitative uptake on 123I-meta-iodobenzylguanidine (MIBG) single-photon emission computed tomography with computed tomography (SPECT/CT). MATERIALS AND METHODS: An 11-year retrospective review of image-guided biopsy on 66 patients (30 female), with a median age of 8.7 years (range, 0.9-49 years), who underwent 95 biopsies (55 bone and 40 soft tissue) of relapsed or refractory neuroblastoma lesions was performed. RESULTS: There were seven minor complications (7%) and one major complication (1%). Neuroblastoma was detected in 88% of MIBG- or fluorodeoxyglucose-avid foci. The overall NGS adequacy was 69% (64% in bone and 74% in soft tissue, P = .37). NGS adequacy within neuroblastoma-positive biopsies was 88% (82% bone and 96% soft tissue, P = .11). NGS-adequate biopsies had a greater mean TC% than inadequates (51% v 18%, P = .03). NGS-adequate biopsies had a higher mean number of needle passes (7.5 v 3.4, P = .0002). The mean tissue volume from NGS-adequate soft-tissue lesions was 0.16 cm3 ± 0.12. Lesion:liver and lesion:psoas MIBG uptake ratios correlated with TC% (r = 0.74, r = 0.72, and n = 14). Mean TC% in NGS-adequate samples was 51%, corresponding to a lesion:liver ratio of 2.9 and a lesion:psoas ratio of 9.0. Thirty percent of biopsies showed an actionable ALK mutation or other therapeutically relevant variant. CONCLUSION: Image-guided biopsy for relapsed or refractory neuroblastoma was safe and likely to provide NGS data to guide therapy decisions. A lesion:liver MIBG uptake ratio of ≥ 3 or a lesion:psoas ratio of > 9 was associated with a TC% sufficient to deliver NGS results.


Assuntos
3-Iodobenzilguanidina , Biópsia Guiada por Imagem , Recidiva Local de Neoplasia/patologia , Neuroblastoma/genética , Neuroblastoma/patologia , Compostos Radiofarmacêuticos , Tomografia Computadorizada com Tomografia Computadorizada de Emissão de Fóton Único , Sequenciamento Completo do Genoma , 3-Iodobenzilguanidina/farmacocinética , Adolescente , Adulto , Criança , Pré-Escolar , Correlação de Dados , Feminino , Humanos , Biópsia Guiada por Imagem/efeitos adversos , Lactente , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/metabolismo , Neuroblastoma/metabolismo , Compostos Radiofarmacêuticos/farmacocinética , Estudos Retrospectivos , Adulto Jovem
5.
Chem Biol Drug Des ; 98(1): 182-191, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33982434

RESUMO

In vivo receptor targeting with radiolabelled peptide-based probes is an attractive approach for the development of novel radiotracers for molecular imaging. This work presents the development and characterization of two novel neuropeptide Y analogues labelled with a positron emitter 68 Ga, for potential use in breast cancer imaging. Both analogues share the same amino acid sequence and were derivatized with NOTA through either a lysine linker (L1) or an acetylated lysine (L2). In both cases, a single product with radiochemical purity higher than 95% was obtained. The two complexes were hydrophilic, showed remarkable in vitro stability, good cellular uptake, binding affinity in the nanomolar range and high cellular internalization rate. Biodistribution studies revealed low blood uptake and elimination through the urinary tract. The addition of an acetyl group in the spacer increased the lipophilicity of C2 and modified the reactivity of the ε-amino group of the lysine which resulted in lower protein binding and lower percentage of injected dose in bladder and urine. The tumour versus muscle ratio was (3.8 ± 0.4) for 68 Ga-L1 and (4.7 ± 0.4) for 68 Ga-L2. These results encourage performing further studies in order to complete the evaluation of both tracers as potential radiopharmaceutical for breast cancer imaging.


Assuntos
Neoplasias da Mama/diagnóstico por imagem , Radioisótopos de Gálio/química , Neuropeptídeo Y/química , Compostos Radiofarmacêuticos/química , Aminas/química , Sequência de Aminoácidos , Animais , Transporte Biológico , Cinerradiografia , Feminino , Humanos , Lisina/química , Camundongos Nus , Neoplasias Experimentais , Neuropeptídeo Y/sangue , Neuropeptídeo Y/farmacocinética , Neuropeptídeo Y/urina , Ligação Proteica , Compostos Radiofarmacêuticos/sangue , Compostos Radiofarmacêuticos/farmacocinética , Compostos Radiofarmacêuticos/urina , Coloração e Rotulagem , Relação Estrutura-Atividade , Distribuição Tecidual
6.
AAPS PharmSciTech ; 22(3): 115, 2021 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-33763814

RESUMO

Nanomedicine is a highly demanded discipline. Liposomes have seen an increased attention due to their physicochemical properties that allow them to act as nanocarriers of drugs and also of radioisotopes that can be used to diagnose and treat cancer. In order to obtain a novel permeability cancer imaging agent based on 99mTc-labeled liposomes, we describe microwave-assisted synthesis of stearyl 6-(benzylidenehydrazinyl) nicotinamide lipid, which was included in two formulations: nanometric hydrazinonicotinic acid (HYNIC) liposome and its PEGylated coated analogue, HYNIC-PEG liposome. Radiolabeling with 99mTc via stearyl 6-(benzylidenehydrazinyl) nicotinamide was found to be easy, reproducible, and stable, revealing high radiochemical purity (94 ± 1.7%) for both liposomal formulations. Biodistribution at 4 h and 24 h and scintigraphic images at 4 h were performed in normal and melanoma-bearing C57BL/6 mice. Biodistribution studies at 4 h showed tumor uptake of 99mTc-HYNIC liposome and 99mTc-HYNIC-PEG liposome (1.1 ± 0.6 and 2.5 ± 0.4, respectively) and also at 24 h p.i. (1.8 ± 0.5 and 3.0 ± 1.1, respectively). Scintigraphic images showed appreciable tumor uptake in melanoma tumor-bearing mice with both liposomal formulations. Our results show that 99mTc stearyl 6-(benzylidenehydrazinyl) nicotinamide liposomes can be used as diagnostic noninvasive in vivo tumor-targeting agents capable of evaluating tumor permeability and development who can be used in personalized chemotherapy planning.


Assuntos
Melanoma Experimental/metabolismo , Niacinamida/farmacocinética , Compostos Radiofarmacêuticos/farmacocinética , Tecnécio/farmacocinética , Animais , Linhagem Celular Tumoral , Lipossomos , Melanoma Experimental/tratamento farmacológico , Camundongos , Camundongos Endogâmicos C57BL , Niacinamida/administração & dosagem , Niacinamida/química , Permeabilidade/efeitos dos fármacos , Cintilografia/métodos , Compostos Radiofarmacêuticos/administração & dosagem , Compostos Radiofarmacêuticos/química , Tecnécio/administração & dosagem , Tecnécio/química , Distribuição Tecidual/efeitos dos fármacos , Distribuição Tecidual/fisiologia , Microambiente Tumoral/efeitos dos fármacos , Microambiente Tumoral/fisiologia
7.
PLoS One ; 15(10): e0238704, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33035214

RESUMO

The aim of this work was to use TOPAS Monte Carlo simulations to model the effect of magnetic fields on dose distributions in brachytherapy lung treatments, under ideal and clinical conditions. Idealistic studies were modeled consisting of either a monoenergetic electron source of 432 keV, or a polyenergetic electron source using the spectrum of secondary electrons produced by 192Ir gamma-ray irradiation. The electron source was positioned in the center of a homogeneous, lung tissue phantom (ρ = 0.26 g/cm3). Conversely, the clinical study was simulated using the VariSource VS2000 192Ir source in a patient with a lung tumor. Three contoured volumes were considered: the tumor, the planning tumor volume (PTV), and the lung. In all studies, dose distributions were calculated in the presence or absence of a constant magnetic field of 3T. Also, TG-43 parameters were calculated for the VariSource and compared with published data from EGS-brachy (EGSnrc) and PENELOPE. The magnetic field affected the dose distributions in the idealistic studies. For the monoenergetic and poly-energetic studies, the radial distance of the 10% iso-dose line was reduced in the presence of the magnetic field by 64.9% and 24.6%, respectively. For the clinical study, the magnetic field caused differences of 10% on average in the patient dose distributions. Nevertheless, differences in dose-volume histograms were below 2%. Finally, for TG-43 parameters, the dose-rate constant from TOPAS differed by 0.09% ± 0.33% and 0.18% ± 0.33% with respect to EGS-brachy and PENELOPE, respectively. The geometry and anisotropy functions differed within 1.2% ± 1.1%, and within 0.0% ± 0.3%, respectively. The Lorentz forces inside a 3T magnetic resonance machine during 192Ir brachytherapy treatment of the lung are not large enough to affect the tumor dose distributions significantly, as expected. Nevertheless, large local differences were found in the lung tissue. Applications of this effect are therefore limited by the fact that meaningful differences appeared only in regions containing air, which is not abundant inside the human.


Assuntos
Braquiterapia/métodos , Neoplasias Pulmonares/radioterapia , Pulmão/efeitos da radiação , Campos Magnéticos , Braquiterapia/estatística & dados numéricos , Simulação por Computador , Relação Dose-Resposta à Radiação , Elétrons , Humanos , Radioisótopos de Irídio/administração & dosagem , Radioisótopos de Irídio/farmacocinética , Radioisótopos de Irídio/uso terapêutico , Imageamento por Ressonância Magnética , Método de Monte Carlo , Imagens de Fantasmas , Compostos Radiofarmacêuticos/administração & dosagem , Compostos Radiofarmacêuticos/farmacocinética , Compostos Radiofarmacêuticos/uso terapêutico , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador , Distribuição Tecidual
8.
Bioorg Chem ; 104: 104185, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32911200

RESUMO

Phosphonates-based agents are well-known bone-seeking radiopharmaceuticals with application in detection and therapy. With higher sensitivity and resolution offered by Positron Emission Tomography (PET), tracers based on this technique are gaining huge attention. 68Ga-based generator and radiotracers render independence from the on-site cyclotron. We report the development of 68Ga-labeled DOTA-based bismacrocyclic phosphonate derivative, for bone PET imaging. The synthesis and characterization of 68Ga- DO3P-AME-DO3P was carried out in > 95% purity. The radiotracer displayed high stability and low binding affinity (<3%) to blood serum. High in vitro binding affinity were observed for synthetic hydroxyapatite, SAOS-2, osteoclast and osteoblast cells. In vivo pharmacokinetics revealed fast washout with biphasic release pattern. The deposition of radiotracer in osseous tissues was high (Bone/Muscle ratio:18), as studied from the biodistribution studies. In vivo PET/CT and biodistribution analyses revealed the ability of 68Ga-DO3P-AME-DO3P to target and accumulate in bone, thus displaying its potential as a PET bone imaging agent.


Assuntos
Acetamidas/química , Osso e Ossos/diagnóstico por imagem , Compostos Macrocíclicos/química , Compostos Organofosforados/química , Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos/química , Acetamidas/sangue , Acetamidas/farmacocinética , Radioisótopos de Gálio , Humanos , Compostos Macrocíclicos/sangue , Compostos Macrocíclicos/farmacocinética , Estrutura Molecular , Compostos Organofosforados/sangue , Compostos Organofosforados/farmacocinética , Compostos Radiofarmacêuticos/sangue , Compostos Radiofarmacêuticos/farmacocinética , Distribuição Tecidual
9.
Nucl Med Biol ; 88-89: 14-23, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32663774

RESUMO

Radiolabeled peptides with high specificity to receptors expressed on tumor cells hold a great promise as diagnostic and therapeutic tracers. The main objective of this study was to evaluate the radiochemical and biological properties of two [131I]I-peptides, as well as their interaction with the epidermal growth factor receptor (EGFR), overexpressed in a wide variety of tumors, including glioblastoma. The EEEEYFELV peptide and its analogue DEDEYFELV, both designed to interact with EGFR, were chemically synthesized, purified and radiolabeled with iodine-131 ([131I]NaI). The radioiodination was evaluated and optimized using the chloramine-T methodology. The stability, serum proteins binding and partition coefficient were assessed for both radioconjugates. Moreover, the binding and internalization of synthesized radiopeptides with rat glioblastoma cells (C6) and with rat brain homogenates from a glioblastoma induced model were evaluated and ex vivo biodistribution studies were performed. Under optimized radiolabeling conditions, the peptides showed an average radiochemical yield of 90-95%. The stability studies showed that both peptides were stable up to 24 h in reaction medium, saline, and human serum. Furthermore, [131I]I-peptides have hydrophilic features and showed binding percentage to serum proteins of around 50%, which is highly compatible with clinical applications. Moreover, the radiopeptides presented capacity for binding and internalization in both tumor cells (C6) and rat brain tissues after tumor induction. Biodistribution studies corroborated the cell culture studies and confirmed the different binding characteristics derived from a simple change of two amino acids (Glu ➔ Asp1,3) in their sequences. The results obtained are consistent enough to motivate further studies. Thereby, these radiolabeled peptides might be useful for diagnostic applications.


Assuntos
Neoplasias Encefálicas/patologia , Glioblastoma/patologia , Radioisótopos do Iodo/farmacocinética , Fragmentos de Peptídeos/metabolismo , Compostos Radiofarmacêuticos/farmacocinética , Animais , Apoptose , Neoplasias Encefálicas/metabolismo , Proliferação de Células , Receptores ErbB/metabolismo , Glioblastoma/metabolismo , Masculino , Ratos , Ratos Sprague-Dawley , Distribuição Tecidual , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
10.
Contrast Media Mol Imaging ; 2020: 2728134, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32489332

RESUMO

Previously, we reported the preparation and preclinical studies of 99mTc-labeled gold nanoparticles-mannose (99mTc-AuNP-mannose) with potential for sentinel lymph node (SLN) detection by using nuclear medicine procedures. This study aimed to evaluate the biokinetics and hybrid (2D/3D) dosimetry of 99mTc-AuNP-mannose in five patients with breast cancer under a sentinel lymph node detection protocol. Anterior and posterior whole-body planar images (2D, at 0.5, 2, 6, and 24 h) and single-photon emission computed tomography (3D at 6.5 h)/computed tomography (SPECT/CT) images were acquired after 99mTc-AuNP-mannose administration (37 MBq). Through a hybrid quantification method, activity in tissues of interest at the different acquisition times was determined and integrated over time to obtain the total nuclear transformations (N), as well as the mean residence time, in each tissue. N values and the OLINDA code were used for estimating the internal radiation absorbed doses. Results demonstrated that 99mTc-AuNP-mannose successfully accumulates and remains up to 24 h in the sentinel lymph node without detectable migration to other lymph nodes and no side effects on patients. Negligible absorption of the radiolabeled nanoparticles into the circulatory system was observed, from which the radio-nanosystem is rapidly eliminated by kidneys. Hybrid (2D/3D) dosimetry evaluations showed equivalent doses to SLN, breast, and kidneys of 172.34, 5.32, and 0.08 mSv/37 MBq, respectively, with an effective dose of 2.05E - 03 mSv/MBq. The mean effective residence time in SLN was 0.92 h. This preliminary study indicates that the use of 99mTc-AuNP-mannose for successful SLN detection in patients is safe, producing an effective dose at the level recommended for diagnostic studies (<10 mSv).


Assuntos
Neoplasias da Mama/diagnóstico por imagem , Ouro/química , Nanopartículas Metálicas/química , Radiometria , Linfonodo Sentinela/diagnóstico por imagem , Adulto , Idoso , Feminino , Ouro/farmacocinética , Humanos , Manose/farmacocinética , Pessoa de Meia-Idade , Compostos Radiofarmacêuticos/farmacocinética , Tomografia Computadorizada com Tomografia Computadorizada de Emissão de Fóton Único , Tecnécio/farmacocinética
11.
J Nucl Cardiol ; 27(1): 173-181, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-29948896

RESUMO

BACKGROUND: 18F-fluorodeoxyglucose (FDG) has been useful in the evaluation of myocardial inflammatory processes. However, it is challenging to identify them due to physiological 18F-FDG uptake. There are no publications demonstrating the application of FDG in post-transplant rejection in humans yet. The aim of this study is to determine the feasibility of suppression of myocardial FDG uptake in post-transplant patients, comparing three different protocols of preparation. METHODS: Ten patients after heart transplantation were imaged by FDG associated with three endomyocardial biopsies (EMB), scheduled in the first year after the procedure. Before each imaging, patients were randomized to one of three preparations: (1) hyperlipidic-hypoglycemic diet; (2) fasting longer than 12 hours; and (3) fasting associated with intravenous heparin. All patients would undergo the three methods. FDG images were analyzed using visual analysis scores and relative radiotracer cardiac uptake (RRCU). RESULTS: The suppression rate of radiotracer activity ranged from 55% to 62%. Visual analysis showed that preparation 3 presented less efficacy in the suppression compared to the others. However, RRCU did not show difference between the preparations. CONCLUSIONS: Suppression of physiological myocardial FDG uptake after cardiac transplantation is feasible. The usefulness of heparin in the suppression is unclear.


Assuntos
Fluordesoxiglucose F18/farmacocinética , Insuficiência Cardíaca/diagnóstico por imagem , Transplante de Coração , Compostos Radiofarmacêuticos/farmacocinética , Tomografia Computadorizada com Tomografia Computadorizada de Emissão de Fóton Único/métodos , Adulto , Anticoagulantes , Dieta com Restrição de Carboidratos , Dieta para Diabéticos , Jejum , Estudos de Viabilidade , Feminino , Insuficiência Cardíaca/metabolismo , Insuficiência Cardíaca/cirurgia , Heparina , Humanos , Masculino , Pessoa de Meia-Idade
12.
Chem Biol Drug Des ; 95(2): 302-310, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31709766

RESUMO

The aim of this work was to develop and evaluate a 99m Tc-labeled neuropeptide Y derivative with affinity toward Y1-receptor. The selected amino acid sequence included nine amino acids derived from the C-terminal portion of the NPY complemented with the addition of one cysteine-mercaptoacetic acid moiety to bind the radiometal. Labeling was achieved through the preparation of a 3 + 1 nitrido complex. Physicochemical evaluation, cell uptake, internalization and externalization studies, and competitive assays were performed. Biodistribution experiments were carried out in normal and tumor-bearing mice. A single product with radiochemical purity >90% and high stability was obtained. In vitro analysis showed specific cellular uptake, IC50 of 73.2 nM, and a high internalization rate (80%). Biodistribution studies showed low blood and renal uptake and combined hepatobiliary and urinary elimination. Preliminary studies in mice bearing induced breast tumors rendered promising uptake values.


Assuntos
Neoplasias da Mama/diagnóstico por imagem , Neuropeptídeo Y/administração & dosagem , Compostos Radiofarmacêuticos/administração & dosagem , Tecnécio/administração & dosagem , Animais , Linhagem Celular Tumoral , Humanos , Camundongos , Compostos Radiofarmacêuticos/farmacocinética , Distribuição Tecidual
13.
Arq. ciências saúde UNIPAR ; 23(3): 221-226, set-dez. 2019.
Artigo em Português | LILACS | ID: biblio-1046191

RESUMO

A Organização Mundial de Saúde (OMS) aponta as doenças cardiovasculares como a principal causa de morte no mundo, caracterizando um grave problema na saúde pública. Os três tipos de doenças que mais acarretam em óbito são: acidente vascular cerebral, seguido de infarto agudo do miocárdio e outras doenças isquêmicas do coração.Apesar dos avanços terapêuticos das últimas décadas, o infarto ainda apresenta altas taxas de mortalidade. Para as pessoas com doenças cardiovasculares ou com alto risco cardiovascular é fundamental o diagnóstico precoce da doença. A cintilografia de perfusão miocárdica é um método de investigação diagnóstica e prognóstico não invasivo de várias doenças cardiovasculares. Esse exame consiste na administração de um radiofármaco para obtenção de imagens de perfusão cardíaca. Dois traçadores marcados com Tecnécio-99m são amplamente utilizados na clínica, porém, esses dois radiofármacos não atendem aos requisitos de um agente de perfusão ideal, por sofrerem significativa excreção biliar, produzindo artefatos na imagem, o que pode inteferir um diagnóstico preciso, já que a qualidade é comprometida, e prolongando o tempo de obtenção da imagem após a administração do radiotraçador. Para superar essa lacuna, pesquisadores vêm estudando novos complexos catiônicos marcados com o Tecnécio. O objetivo desse artigo é fazer uma revisão, abordando a literatura sobre os radiofármacos que estão sendo estudados, suas vantagens e desvantagens sobre os traçadores já utilizados, e sobre sua potencial utilização na obtenção de imagem de perfusão cardíaca.


The World Health Organization (WHO) acknowledges cardiovascular diseases as the leading cause of death in the world, being regarded as a serious public health issue. The three types of diseases with the greatest mortality are: stroke, followed by acute myocardial infarction (AMI) and other ischemic heart diseases. Despite the therapeutic advances of the last decades, AMI still presents high mortality rates. Early diagnosis is essential for people with cardiovascular diseases or with a high cardiovascular risk. Myocardial perfusion scintigraphy is a method of diagnostic investigation and noninvasive prognosis of various cardiovascular diseases. This examination consists in the administration of a radiopharmaceutical drug to obtain images of cardiac perfusion. Two tracers labeled with Technetium-99m are widely used, however, these two radiopharmaceuticals do not meet the requirements of an ideal perfusion agent, because they have a high liver absorption, producing artifacts in the image, which can disrupt a precise diagnosis, since the quality is compromised, and prolonging the imaging time after administration of the radioisotope. To overcome this gap, researchers have been studying new cationic complexes marked with technetium. The objective of this article is to review the literature on the radiopharmaceuticals being studied, their advantages and disadvantages on the tracers already used, and their potential use in obtaining a cardiac perfusion image.


Assuntos
Tecnécio/farmacocinética , Compostos Radiofarmacêuticos/farmacocinética , Imagem de Perfusão do Miocárdio/instrumentação , Traçadores Radioativos , Doenças Cardiovasculares/diagnóstico por imagem , Cintilografia/instrumentação , Tecnécio Tc 99m Sestamibi/efeitos adversos , Técnicas de Imagem Cardíaca/instrumentação , Fígado/efeitos dos fármacos , Infarto do Miocárdio/diagnóstico por imagem
14.
Appl Radiat Isot ; 154: 108854, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31442798

RESUMO

Estrogen receptors are overexpressed in 70% of breast cancer and identification of their presence is important to select the appropriate treatment. This work proposes the preparation and evaluation of an estradiol derived as potential ER imaging agent. Ethinylestradiol was derivatized to introduce a dithiocarbamate function for Tc coordination. Labeling was achieved through the formation of a symmetric Tc(V)-nitrido complex with a radiochemical purity (RCP) > 95%. Physicochemical evaluation, cell uptake, biodistribution in normal animals and in nude mice bearing induced ER + breast tumors showed promising results.


Assuntos
Neoplasias da Mama/diagnóstico por imagem , Compostos de Organotecnécio , Compostos Radiofarmacêuticos , Animais , Neoplasias da Mama/metabolismo , Estabilidade de Medicamentos , Estradiol/análogos & derivados , Estradiol/síntese química , Estradiol/química , Feminino , Humanos , Células MCF-7 , Camundongos , Camundongos Nus , Transplante de Neoplasias , Compostos de Organotecnécio/síntese química , Compostos de Organotecnécio/química , Compostos de Organotecnécio/farmacocinética , Ligação Proteica , Compostos Radiofarmacêuticos/síntese química , Compostos Radiofarmacêuticos/química , Compostos Radiofarmacêuticos/farmacocinética , Ratos , Ratos Wistar , Receptores de Estrogênio/metabolismo , Distribuição Tecidual
16.
Int J Radiat Biol ; 95(11): 1547-1551, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31290704

RESUMO

Purpose: This study evaluated if Toxoplasma gondii infection and the drug-associated infection modifies the brain radiopharmaceutical Ethylene Cystine Diethylester Dihydrochloride (99mTc-ECD) biodistribution in mice.Materials and methods: A total of 18 mice were divided into 3 groups. Control group (C) received distilled water and 99mTc-ECD; Infected group (I) received T. gondii strain and 99mTc-ECD; Infected and Treated group (IT), in addition to infection, received association of Pyrimethamine and Sulfadiazine and 99mTc-ECD. The T. gondii strain used in this study was TgCkRrRN3. Forty minutes after administration of the 99mTc-ECD, all animals were euthanized, and blood and brain samples were isolated. The counting of the radioactivity percentage per gram of tissue (%ATI/g) was calculated, and statistical analysis was performed by t-test, with a level of significance of p < .05.Results: There was a significant increase in %ATI/g between groups C and I on brain (0.35 ± 0.02 and 0.45 ± 0.04; p = .041) and on blood (0.80 ± 0.09 and 1.14 ± 0.31; p = .049). A significant decrease in %ATI/g occurred between groups C and IT on blood (0.80 ± 0.09 and 0.54 ± 0.08; p = .001) and on brain (0.35 ± 0.02 and 0.22 ± 0.04; p = .049).Conclusions: Combined therapy of anti-Toxoplasma drugs in infected mice reduced the uptake of 99mTc-ECD, probably due to its binding to plasma proteins.


Assuntos
Encéfalo/parasitologia , Encéfalo/efeitos da radiação , Cisteína/análogos & derivados , Compostos de Organotecnécio/farmacocinética , Compostos Radiofarmacêuticos/farmacocinética , Toxoplasma , Toxoplasmose/tratamento farmacológico , Toxoplasmose/parasitologia , Animais , Antiprotozoários/uso terapêutico , Encéfalo/metabolismo , Cisteína/farmacocinética , Masculino , Camundongos , Pirimetamina/uso terapêutico , Sulfadiazina/uso terapêutico , Distribuição Tecidual
17.
J Biomed Opt ; 24(7): 1-10, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31313539

RESUMO

Cerenkov radiation (CR) is the emission of UV-vis light generated by the de-excitation of the molecules in the medium, after being polarized by an excited particle traveling faster than the speed of light. When ß particles travel through tissue with energies greater than 219 keV, CR occurs. Tissues possess a spectral optical window of 600 to 1100 nm. The CR within this range can be useful for quantitative preclinical studies using optical imaging and for the in-vivo evaluation of Lu177-radiopharmaceuticals (ß-particle emitters). The objective of our research was to determine the experimental emission light spectrum of Lu177-CR and evaluate its transmission properties in tissue as well as the feasibility to applying CR imaging in the preclinical studies of Lu177-radiopharmaceuticals. The theoretical and experimental characterizations of the emission and transmission spectra of Lu177-CR in tissue, in the vis-NIR region (350 to 900 nm), were performed using Monte Carlo simulation and UV-vis spectroscopy. Mice Lu177-CR images were acquired using a charge-coupled detector camera and were quantitatively analyzed. The results demonstrated good agreement between the theoretical and the experimental Lu177-CR emission spectra. Preclinical CR imaging demonstrated that the biokinetics of Lu177-radiopharmaceuticals in the main organs of mice can be acquired.


Assuntos
Lutécio , Imagem Óptica/métodos , Radioisótopos , Compostos Radiofarmacêuticos , Animais , Partículas beta , Linhagem Celular Tumoral , Radiação Eletromagnética , Estudos de Viabilidade , Humanos , Lutécio/química , Lutécio/farmacocinética , Camundongos , Camundongos Nus , Neoplasias Experimentais/diagnóstico por imagem , Neoplasias Experimentais/radioterapia , Radioisótopos/química , Radioisótopos/farmacocinética , Compostos Radiofarmacêuticos/química , Compostos Radiofarmacêuticos/farmacocinética
18.
Contrast Media Mol Imaging ; 2019: 4087895, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31178670

RESUMO

D-α-Tocopheryl polyethylene glycol 1000 succinate (TPGS) is a Food and Drug Administration (FDA) approved biomaterial that can form nanosized micelles in aqueous solution. TPGS micelles stand as an interesting system to perform drug delivery as they can carry lipophilic drugs and overcome P glycoprotein efflux as well. Therefore, TPGS micelles combined with other copolymers have been reported in many cancer research studies as a carrier for therapeutic drugs. Their ability to reach tumoral tissue can also be exploited to develop imaging agents with diagnostic application. A radiolabeling method with 99mTc for TPGS nanosized micelles and their biodistribution in a healthy animal model as well as their pharmacokinetics and radiolabeling stability in vivo was previously reported. The aim of this work was to evaluate the performance of this radioactive probe as a diagnostic imaging agent compared to routinely available SPECT radiopharmaceutical, 99mTc-sestamibi. A small field of view gamma camera was used for scintigraphy studies using radiolabeled TPGS micelles in two animal models of breast cancer: syngeneic 4T1 murine cell line (injected in BALB/c mice) and chemically NMU-induced (Sprague-Dawley rats). Ex vivo radioactivity accumulation in organs of interest was measured by a solid scintillation counter, and a semiquantitative analysis was performed over acquired images as well. Results showed an absence of tumoral visualization in 4T1 model for both radioactive probes by gamma camera imaging. On the contrary, NMU-induced tumors had a clear tumor visualization by scintigraphy. A higher tumor/background ratio and more homogeneous uptake were found for radiolabeled TPGS micelles compared to 99mTc-sestamibi. In conclusion, 99mTc-radiolabeled TPGS micelles might be a potential SPECT imaging probe for diagnostic purposes.


Assuntos
Neoplasias da Mama/diagnóstico por imagem , Micelas , Nanoestruturas , Compostos Radiofarmacêuticos , Tomografia Computadorizada de Emissão de Fóton Único/métodos , Vitamina E , Animais , Avaliação Pré-Clínica de Medicamentos , Estabilidade de Medicamentos , Feminino , Humanos , Neoplasias Mamárias Experimentais/induzido quimicamente , Neoplasias Mamárias Experimentais/diagnóstico por imagem , Metilnitrosoureia , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C3H , Compostos Radiofarmacêuticos/farmacocinética , Ratos Sprague-Dawley , Tecnécio Tc 99m Sestamibi/farmacocinética , Distribuição Tecidual , Vitamina E/farmacocinética
20.
Clin Transl Oncol ; 21(4): 499-504, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30229391

RESUMO

PURPOSE: The standard treatment for patients with stage III non-small cell lung cancer (NSCLC), unsuitable for resection and with good performance, is definitive radiotherapy with cisplatin-based chemotherapy. Our aim is to evaluate the effect of the maximum value of standardized uptake values (SUVmax) of the primary tumor in positron emission tomography-computed tomography (PET/CT) before treatment on complete response (CR) and overall survival. METHODS: The data of 73 stage III NSCLC patients treated with concurrent definitive chemoradiotherapy (CRT) between 2008 and 2017 and had PET/CT staging in the pretreatment period were evaluated. ROC curve analysis was performed to determine the ideal cut-off value of pretreatment SUVmax to predict CR. RESULTS: Median age was 58 years (range 27-83 years) and 66 patients were male (90.4%). Median follow-up time was 18 months (range 3-98 months); median survival was 23 months. 1-year overall survival (OS) rate and 5-year OS rate were 72 and 19%, respectively. Median progression-free survival (PFS) was 9 months; 1-year PFS rate and 5-year PFS rate were 38 and 19%, respectively. The ideal cut-off value of pretreatment SUVmax that predicted the complete response of CRT was 12 in the ROC analysis [AUC 0.699 (0.550-0.833)/P < 0.01] with a sensitivity of 83%, and specificity of 55%. In patients with SUVmax < 12, CR rate was 60%, while, in patients with SUV ≥ 12, it was only 19% (P = 0.002). Median OS was 26 months in patients with pretreatment SUVmax < 12, and 21 months in patients with SUVmax ≥ 12 (HR = 2.93; 95% CI 17.24-28.75; P = 0.087). CR rate of the whole patient population was 26%, and it was the only factor that showed a significant benefit on survival in both univariate and multivariate analyses. CONCLUSION: Pretreatment SUVmax of the primary tumor in PET/CT may predict CR in stage III NSCLC patients who were treated with definitive CRT. Having clinical CR is the only positive predictive factor for prolonged survival.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/radioterapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/patologia , Quimiorradioterapia , Feminino , Fluordesoxiglucose F18/farmacocinética , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Prognóstico , Curva ROC , Compostos Radiofarmacêuticos/farmacocinética , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA