RESUMO
Aß42 plaque formation is one of the preliminary pathologic events that occur post traumatic brain injury (TBI) which is also among the most noteworthy hallmarks of AD. Their pre symptomatic detection is therefore vital for better disease management. Chalcone-picolinic acid chelator derivative, 6-({[(6-carboxypyridin-2-yl)methyl](2-{4-[(2E)-3-[4-(dimethyl amino)phenyl]prop-2-enoyl]phenoxy}ethyl)amino}methyl)pyridine-2-carboxylic acid, Py-chal was synthesized to selectively identify amyloid plaques formed post head trauma using SPECT imaging by stable complexation to 99mTc with > 97% efficiency without compromising amyloid specificity. The binding potential of the Py-chal ligand to amyloid plaques remained high as confirmed by in vitro binding assay and photophysical spectra. Further, the Py-chal complex stained amyloid aggregates in the brain sections of rmTBI mice model. In vivo scintigraphy in TBI mice model displayed high uptake followed by high retention while the healthy rabbits displayed higher brain uptake followed by a rapid washout attributed to absence of amyloid plaques. Higher uptake in brain of TBI model was also confirmed by ex vivo biodistribution analysis wherein brain uptake of 3.38 ± 0.2% ID/g at 2 min p.i. was observed for TBI mice model. This was followed by prolonged retention and more than twofold higher activity as compared to sham mice brain. This preliminary data suggests the specificity of the radiotracer for amyloid detection post head trauma and applicability of 99mTc labeled Py-chal complex for TBI-induced ß-amyloid SPECT imaging.
Assuntos
Peptídeos beta-Amiloides , Lesões Encefálicas Traumáticas , Chalcona , Tomografia Computadorizada de Emissão de Fóton Único , Animais , Masculino , Camundongos , Peptídeos beta-Amiloides/metabolismo , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Lesões Encefálicas Traumáticas/diagnóstico por imagem , Lesões Encefálicas Traumáticas/metabolismo , Chalcona/química , Chalcona/farmacologia , Traumatismos Craniocerebrais/diagnóstico por imagem , Compostos de Organotecnécio/química , Compostos de Organotecnécio/farmacocinética , Compostos Radiofarmacêuticos/química , Compostos Radiofarmacêuticos/farmacocinética , Compostos Radiofarmacêuticos/síntese química , Tecnécio/química , Tecnécio/farmacologia , Distribuição TecidualRESUMO
BACKGROUND: 5-azacitidine is a very potent chemotherapeutic agent that suffers from certain disadvantages. OBJECTIVE: This study aims to prepare gold nanoparticles as a new nano-formula of 5-azacitidine that can improve its bioavailability and decrease its side effects. METHODS: 5-azacytidine-loaded GA-AuNPs were prepared and characterized by UV-Vis spectroscopy, infrared (IR), and electronic transmission microscope (TEM). This new platform was characterized in vitro by measuring its zeta potential, particle size, and drug loading efficacy, and the anti-proliferative effect on the MCF-7 cell line was evaluated. In vivo biodistribution studies of 99mTc-5-aza solution and 99mTc-5-aza-gold nano formula were conducted in tumor-bearing mice by different routes of administration (intravenous and intra-tumor). RESULTS: 5-Aza-GA-AuNPs formula was successfully prepared with an optimum particle size of ≈34.66 nm, the zeta potential of -14.4 mV, and high entrapment efficiency. 99mTc-5-Aza-GA-AuNPs were successfully radiosynthesized with a labeling yield of 95.4%. Biodistribution studies showed high selective accumulation in tumor and low uptake in non-target organs in the case of the 5-Aza-GA-AuNPs formula than the 99mTc-5-azacitidine solution. CONCLUSION: 99mTc-5-Aza-GA-AuNPs improved the selectivity and uptake of 5-azacitidine in cancer. Moreover, 99mTc-5-Aza-GA-AuNPs could be used as hopeful theranostic radiopharmaceutical preparation for cancer.
Assuntos
Ouro , Nanopartículas Metálicas , Camundongos , Animais , Ouro/química , Azacitidina/farmacologia , Distribuição Tecidual , Nanopartículas Metálicas/química , Compostos Radiofarmacêuticos , Tecnécio/química , Tecnécio/farmacologiaRESUMO
Lung cancer (LC) is a common type of cancer, which is a leading cause of death around the world. There is an urgency for the development of new drugs that could diagnose the LC in the early stages and in a precise manner. In this direction, the development of nanoparticles radiolabeled with the diagnostic radioisotopes represent an important advance in the field of cancer imaging. In this study were developed PLA/PVA/Atezolizumab nanoparticles which were radiolabeled with 99mTc (Technetium-99m). The radiolabeled nanoparticles were evaluated in both: in-vitro (L-929 and A-549) as in-vivo (mice). The results showed no cytotoxicity effect in the healthy cells (L-929) and cytotoxicity effect in the tumor cells (A-549). The biodistribution assay demonstrated that 99mTc-PLA/PVA/Atezolizumab could reach the tumor site 14-folds higher than the nonparticulate atezolizumab. In conclusion, 99mTc-PLA/PVA/Atezolizumab nanoparticles showed to be a new drug which is able to precisely image the lung tumor, and it must be considered for clinical trials.
Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Nanopartículas , Animais , Anticorpos Monoclonais Humanizados , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/tratamento farmacológico , Camundongos , Poliésteres , Compostos Radiofarmacêuticos , Tecnécio/farmacologia , Distribuição TecidualRESUMO
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
BACKGROUND: Prostate-specific membrane antigen (PSMA)-targeted radioligand therapy (RLT) may be associated with renal toxicity. We aimed to identify predictive parameters for the development of chronic kidney disease (CKD) in patients with metastatic castration resistant prostate cancer (mCRPC) undergoing RLT. METHODS: In 46 mCRPC patients scheduled for Lu-177-PSMA-RLT, pretherapeutic estimated glomerular filtration rate (eGFR [ml/min/1.73 m2 ]), Tc-99m-mercaptoacetyltriglycine (Tc-99m-MAG3) clearance and baseline Ga-68-PSMA-ligand positron emission tomography (PET)-derived renal cortical uptake and PSMA-tumor volume (TV) were determined. We tested the predictive capability of these parameters and clinical risk factors for the occurrence of CKD (defined as CTCAE vers. 5.0 grade 2 or higher) during follow-up. RESULTS: After 4 ± 3 cycles of RLT average eGFR declined from 76 ± 17 to 72 ± 20 ml/min/1.73 m2 (p = 0.003). Increased estimated renal radiation dose (eRRD) was significantly associated with renal functional decline (p = 0.008). During follow-up, 16/46 (30.4%) developed CKD grade 2 (no grade 3 or higher). In receiver operating characteristic (ROC) analysis, pretherapeutic eGFR was highly accurate in identifying the occurrence of CKD vs no CKD with an area under the curve (AUC) of 0.945 (p < 0.001; best threshold, 77 ml/min/1.73 m2 ), followed by Tc-99m-MAG3-derived tubular extraction rate (TER; AUC, 0.831, p < 0.001; best threshold, 200 ml/min/1.73 m2 ). Renal PET signal (p = 0.751) and PSMA-TV (p = 0.942), however, were not predictive. Kaplan-Meier analyses revealed adverse renal outcome for patients with lower eGFR (p = 0.001) and lower scintigraphy-derived TER (p = 0.009), with pretherapeutic eGFR emerging as the sole predictive parameter in multivariate analysis (p = 0.007). CONCLUSION: Serious adverse renal events are not a frequent phenomenon after PSMA-targeted RLT. However, in patients developing moderate CKD after RLT, pretherapeutic eGFR is an independent predictor for renal impairment during follow-up.
Assuntos
Antígenos de Superfície , Glutamato Carboxipeptidase II , Lutécio , Neoplasias de Próstata Resistentes à Castração , Radioimunoterapia , Radioisótopos , Insuficiência Renal Crônica , Antígenos de Superfície/imunologia , Antígenos de Superfície/metabolismo , Taxa de Filtração Glomerular , Glutamato Carboxipeptidase II/imunologia , Glutamato Carboxipeptidase II/metabolismo , Humanos , Estimativa de Kaplan-Meier , Lutécio/administração & dosagem , Lutécio/efeitos adversos , Masculino , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons/métodos , Neoplasias de Próstata Resistentes à Castração/patologia , Neoplasias de Próstata Resistentes à Castração/terapia , Radioimunoterapia/efeitos adversos , Radioimunoterapia/métodos , Radioisótopos/administração & dosagem , Radioisótopos/efeitos adversos , Eliminação Renal , Insuficiência Renal Crônica/induzido quimicamente , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/prevenção & controle , Risco Ajustado/métodos , Fatores de Risco , Tecnécio/farmacologiaRESUMO
Auger electron-emitters increasingly attract attention as potential radionuclides for molecular radionuclide therapy in oncology. The radionuclide technetium-99m is widely used for imaging; however, its potential as a therapeutic radionuclide has not yet been fully assessed. We used MDA-MB-231 breast cancer cells engineered to express the human sodium iodide symporter-green fluorescent protein fusion reporter (hNIS-GFP; MDA-MB-231.hNIS-GFP) as a model for controlled cellular radionuclide uptake. Uptake, efflux, and subcellular location of the NIS radiotracer [99mTc]TcO4- were characterised to calculate the nuclear-absorbed dose using Medical Internal Radiation Dose formalism. Radiotoxicity was determined using clonogenic and γ-H2AX assays. The daughter radionuclide technetium-99 or external beam irradiation therapy (EBRT) served as controls. [99mTc]TcO4- in vivo biodistribution in MDA-MB-231.hNIS-GFP tumour-bearing mice was determined by imaging and complemented by ex vivo tissue radioactivity analysis. [99mTc]TcO4- resulted in substantial DNA damage and reduction in the survival fraction (SF) following 24 h incubation in hNIS-expressing cells only. We found that 24,430 decays/cell (30 mBq/cell) were required to achieve SF0.37 (95%-confidence interval = [SF0.31; SF0.43]). Different approaches for determining the subcellular localisation of [99mTc]TcO4- led to SF0.37 nuclear-absorbed doses ranging from 0.33 to 11.7 Gy. In comparison, EBRT of MDA-MB-231.hNIS-GFP cells resulted in an SF0.37 of 2.59 Gy. In vivo retention of [99mTc]TcO4- after 24 h remained high at 28.0% ± 4.5% of the administered activity/gram tissue in MDA-MB-231.hNIS-GFP tumours. [99mTc]TcO4- caused DNA damage and reduced clonogenicity in this model, but only when the radioisotope was taken up into the cells. This data guides the safe use of technetium-99m during imaging and potential future therapeutic applications.
Assuntos
Tecnécio/farmacologia , Tecnécio/farmacocinética , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Linhagem Celular Tumoral , Relação Dose-Resposta à Radiação , Humanos , Radioisótopos do Iodo/farmacologia , Compostos Radiofarmacêuticos/farmacologia , Simportadores/genética , Distribuição TecidualRESUMO
Spinal cord injury (SCI) refers to the damage suffered in the spinal cord by any trauma or pathology. The purpose of this work was to determine whether 99mTc-GA-5, a radiotracer targeting Glial Fibrillary Acidic Protein (GFAP), can reveal in vivo the reactivation of astrocytes in a murine model with SCI. A method for the 99mTc radiolabeling of the mouse anti-GFAP monoclonal antibody GA-5 was implemented. Radiochemical characterization was performed, and radioimmunohistochemistry assays were used to evaluate the integrity of 99mTc-GA-5. MicroSPECT/CT was used for in vivo imaging to trace SCI in the rats. No alterations in the GA-5's recognition/specificity ability were observed after the radiolabeling. The GA-5's radiolabeling procedure implemented in this work offers a practical method to allow the in vivo following of this monoclonal antibody to evaluate its biodistribution and specificity for GFAP receptors using SPECT/CT molecular imaging.
Assuntos
Proteína Glial Fibrilar Ácida/genética , Traumatismos da Medula Espinal/diagnóstico por imagem , Medula Espinal/diagnóstico por imagem , Tecnécio/química , Animais , Anticorpos Monoclonais/química , Anticorpos Monoclonais/farmacologia , Modelos Animais de Doenças , Proteína Glial Fibrilar Ácida/imunologia , Proteína Glial Fibrilar Ácida/farmacologia , Humanos , Radioquímica , Compostos Radiofarmacêuticos/farmacologia , Ratos , Tomografia Computadorizada com Tomografia Computadorizada de Emissão de Fóton Único , Medula Espinal/patologia , Traumatismos da Medula Espinal/genética , Traumatismos da Medula Espinal/patologia , Tecnécio/farmacologia , Distribuição Tecidual/efeitos da radiaçãoRESUMO
Other than in animal models of human disease, little functional imaging has been performed in most of the animal world. The aim of this study was to explore the functional anatomy of the European round back slug (Arionidae) and leopard slug (Limacidae) and to establish an imaging protocol for comparative species study. Radionuclide images with single photon emission computed tomography (SPECT) and positron emission tomography (PET) were obtained after injections of standard clinical radiopharmaceuticals 99mtechnetium dicarboxypropane diphosphonate (bone scintigraphy), 99mtechnetium mercaptoacetyltriglycine (kidney function), 99mtechnetium diethylenetriaminepentaacetic acid (kidney function), 99mtechnetium pertechnetate (mediated by the sodium-iodide symporter), 99mtechnetium sestamibi (cardiac scintigraphy) or 18F-fluoro-deoxyglucose (glucose metabolism) in combination with magnetic resonance imaging (MRI) and computed tomography (CT) for uptake anatomic definition. Images were compared with anatomic drawings for the Arionidae species. Additionally, organ uptake data was determined for a description of slug functional anatomy in comparison to human tracer biodistribution patterns identifying the heart, the open circulatory anatomy, calcified shell remnant, renal structure (nephridium), liver (digestive gland) and intestine. The results show the detailed functional anatomy of Arionidae and Limacidae, and describe an in vivo whole-body imaging procedure for invertebrate species.
Assuntos
Gastrópodes/anatomia & histologia , Espectroscopia de Ressonância Magnética , Compostos Radiofarmacêuticos/farmacologia , Tomografia Computadorizada de Emissão de Fóton Único , Animais , Cintilografia , Tecnécio/farmacologia , Distribuição Tecidual , Tomografia Computadorizada por Raios X , Imagem Corporal TotalRESUMO
Radionuclide imaging of HER2 expression in tumours may enable stratification of patients with breast, ovarian, and gastroesophageal cancers for HER2-targeting therapies. A first-generation HER2-binding affibody molecule [99mTc]Tc-ZHER2:V2 demonstrated favorable imaging properties in preclinical studies. Thereafter, the affibody scaffold has been extensively modified, which increased its melting point, improved storage stability, and increased hydrophilicity of the surface. In this study, a second-generation affibody molecule (designated ZHER2:41071) with a new improved scaffold has been prepared and characterized. HER2-binding, biodistribution, and tumour-targeting properties of [99mTc]Tc-labelled ZHER2:41071 were investigated. These properties were compared with properties of the first-generation affibody molecules, [99mTc]Tc-ZHER2:V2 and [99mTc]Tc-ZHER2:2395. [99mTc]Tc-ZHER2:41071 bound specifically to HER2 expressing cells with an affinity of 58 ± 2 pM. The renal uptake for [99mTc]Tc-ZHER2:41071 and [99mTc]Tc-ZHER2:V2 was 25-30 fold lower when compared with [99mTc]Tc-ZHER2:2395. The uptake in tumour and kidney for [99mTc]Tc-ZHER2:41071 and [99mTc]Tc-ZHER2:V2 in SKOV-3 xenografts was similar. In conclusion, an extensive re-engineering of the scaffold did not compromise imaging properties of the affibody molecule labelled with 99mTc using a GGGC chelator. The new probe, [99mTc]Tc-ZHER2:41071 provided the best tumour-to-blood ratio compared to HER2-imaging probes for single photon emission computed tomography (SPECT) described in the literature so far. [99mTc]Tc-ZHER2:41071 is a promising candidate for further clinical translation studies.
Assuntos
Antineoplásicos Imunológicos , Rim , Neoplasias Experimentais , Compostos Radiofarmacêuticos , Receptor ErbB-2/metabolismo , Tecnécio , Tomografia Computadorizada de Emissão de Fóton Único , Animais , Antineoplásicos Imunológicos/química , Antineoplásicos Imunológicos/farmacocinética , Antineoplásicos Imunológicos/farmacologia , Linhagem Celular Tumoral , Feminino , Humanos , Rim/diagnóstico por imagem , Rim/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Neoplasias Experimentais/diagnóstico por imagem , Neoplasias Experimentais/tratamento farmacológico , Neoplasias Experimentais/metabolismo , Compostos Radiofarmacêuticos/síntese química , Compostos Radiofarmacêuticos/química , Compostos Radiofarmacêuticos/farmacocinética , Compostos Radiofarmacêuticos/farmacologia , Tecnécio/química , Tecnécio/farmacocinética , Tecnécio/farmacologia , Distribuição Tecidual , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
For effective Auger therapy of cancer, the Auger-electron emitters must be delivered to the tumor cells in close proximity to a radiosensitive cellular target. Nuclear DNA is considered the most relevant target of Auger electrons to have augmented radiotoxic effects and significant cell death. However, there is a growing body of evidence that other targets, such as the mitochondria, could be relevant subcellular targets in Auger therapy. Thus, we developed dual-targeted 99mTc(I) tricarbonyl complexes containing a triphenylphosphonium (TPP) moiety to promote accumulation of 99mTc in the mitochondria, and a bombesin peptide to provide specificity towards the gastrin releasing peptide receptor (GRPr) overexpressed in prostate cancer cells. The designed dual-targeted complex, 99mTc-TPP-BBN, is efficiently internalized by human prostate cancer PC3 cells through a specific GRPr-mediated mechanism of uptake. Moreover, the radioconjugate provided an augmented accumulation of 99mTc in the mitochondria of the target tumor cells, most probably following its intracellular cleavage by cathepsin B. In addition, 99mTc-TPP-BBN showed an enhanced ability to reduce the survival of PC3 cells, in a dose-dependent manner.
Assuntos
Bombesina/farmacologia , Mitocôndrias/efeitos dos fármacos , Neoplasias da Próstata/radioterapia , Compostos Radiofarmacêuticos/síntese química , Compostos Radiofarmacêuticos/farmacologia , Tecnécio/farmacologia , Animais , Bombesina/química , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos da radiação , Humanos , Masculino , Mitocôndrias/metabolismo , Mitocôndrias/patologia , Neurotransmissores/química , Neurotransmissores/farmacologia , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Receptores da Bombesina/metabolismo , Tecnécio/químicaRESUMO
BACKGROUND: Fluorine-18 flurpiridaz is a novel positron emission tomography (PET) myocardial perfusion imaging tracer. OBJECTIVES: This study sought to assess the diagnostic efficacy of flurpiridaz PET versus technetium-99m-labeled single photon emission computed tomography SPECT for the detection and evaluation of coronary artery disease (CAD), defined as ≥50% stenosis by quantitative invasive coronary angiography (ICA). Flurpiridaz safety was also evaluated. METHODS: In this phase III prospective multicenter clinical study, 795 patients with known or suspected CAD from 72 clinical sites in the United States, Canada, and Finland were enrolled. A total of 755 patients were evaluable, and the mean age was 62.3 ± 9.5 years, 31% were women, 55% had body mass index ≥30 kg/m2, and 71% had pharmacological stress. Patients underwent 1-day rest-stress (pharmacological or exercise) flurpiridaz PET and 1- or 2-day rest-stress Tc-99m-labeled SPECT and ICA. Images were read by 3 experts blinded to clinical and ICA data. RESULTS: Sensitivity of flurpiridaz PET (for detection of ≥50% stenosis by ICA) was 71.9% (95% confidence interval [CI]: 67.0% to 76.3%), significantly (p < 0.001) higher than SPECT (53.7% [95% CI: 48.5% to 58.8%]), while specificity did not meet the prespecified noninferiority criterion (76.2% [95% CI: 71.8% to 80.1%] vs. 86.6% [95% CI: 83.2% to 89.8%]; p = NS). Receiver-operating characteristic curve analysis demonstrated superior discrimination of CAD by flurpiridaz PET versus SPECT in the overall population, in women, obese patients, and patients undergoing pharmacological stress testing (p < 0.001 for all). Flurpiridaz PET was superior to SPECT for defect size (p < 0.001), image quality (p < 0.001), diagnostic certainty (p < 0.001), and radiation exposure (6.1 ± 0.4 mSv vs. 13.4 ± 3.2 mSv; p < 0.001). Flurpiridaz PET was safe and well tolerated. CONCLUSIONS: Flurpiridaz PET myocardial perfusion imaging shows promise as a new tracer for CAD detection and assessment of women, obese patients, and patients undergoing pharmacological stress testing. A second phase III Food and Drug Administration trial is ongoing. (A Phase 3 Multi-center Study to Assess PET Imaging of Flurpiridaz F 18 Injection in Patients with CAD; NCT01347710).
Assuntos
Doença da Artéria Coronariana/diagnóstico , Radioisótopos de Flúor/farmacologia , Imagem de Perfusão do Miocárdio/métodos , Obesidade , Tomografia por Emissão de Pósitrons/métodos , Tecnécio/farmacologia , Doença da Artéria Coronariana/complicações , Teste de Esforço/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/complicações , Obesidade/diagnóstico , Compostos Radiofarmacêuticos/farmacologia , Reprodutibilidade dos Testes , Fatores SexuaisRESUMO
The purpose of this work was to compare the measured red-cell volume (RCV) using sodium pertechnétate [RCV-99mTc] compared to the reference technique using sodium radiochromate [RCV-51Cr] and to assess the influence of technetium-99 elution on the RCV-99mTc value. Ten patients had simultaneous measurements of RCV-99mTc and RCV-51Cr. Elution of Tc-99m from red blood cells was 2.9% and led to an average overestimation of RCV-99mTc of 3.7%. The introduction of individual tracer elution rates in the RCV-99mTc calculation corrects this overestimation.
Assuntos
Radioisótopos de Cromo/farmacologia , Volume de Eritrócitos/efeitos dos fármacos , Eritrócitos/citologia , Eritrócitos/efeitos dos fármacos , Marcação por Isótopo/métodos , Tecnécio/farmacologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Relação Dose-Resposta a Droga , Contagem de Eritrócitos/métodos , Feminino , Hematócrito/métodos , Humanos , Marcação por Isótopo/efeitos adversos , Masculino , Pessoa de Meia-Idade , Técnica de Diluição de RadioisótoposRESUMO
Hyaluronan (HA) have been widely used as the ideal biomaterials. It is important to understand their degradation and distribution for better optimization. From a new aspect of using radiotracers, we designed the HA-tyramine-bisphosphonate derivative for dual-labelling with two radionuclides (99mTc and 131I) simultaneously for in vitro and in vivo tracking. This dual-radiolabelled HA derivative can still be non-covalently crosslinked by hydroxyapatites to form injectable gel. The excellent properties of the gel, such as robust, biodegradable, and self-healing capacity were maintained. We firstly proved the possibility to distinguish different radionuclides in the degraded gel using the high-resolution gamma-ray spectrometry. The radiolabelled gel showed lower toxicity than pure hydroxyapatites against various cell lines, while the in vivo results proved that the 99mTc/131I-labelling of the gel was safe and stable enough for imaging and quantitatively tracking. The present method can also be applied for the development of dual-radiolabelled gels from other polysaccharides.
Assuntos
Meios de Contraste/farmacologia , Difosfonatos/química , Géis/química , Radioisótopos/química , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Plásticos Biodegradáveis/química , Plásticos Biodegradáveis/farmacologia , Meios de Contraste/química , Difosfonatos/farmacologia , Raios gama , Géis/farmacologia , Humanos , Ácido Hialurônico/química , Radioisótopos do Iodo/química , Radioisótopos do Iodo/farmacologia , Radioisótopos/farmacologia , Análise Espectral , Tecnécio/química , Tecnécio/farmacologia , Engenharia Tecidual/métodos , Tiramina/química , Tiramina/farmacologiaRESUMO
Cellulose nanocrystals (CNCs) are known as nano-biomaterials that can be achieved from the different sources. The designated CNCs have been successfully fabricated from the roots of Dorema kopetdaghens (Dk) plant by sulphuric acid hydrolysis method. Structural analysis has been carried out by the means of XRD, FTIR, and TGA/DTG procedures. The XRD results have indicated that the crystalline structure of CNCs had been cellulose I with the crystallinity index of 83.20% and size of 4.95 nm. The FTIR spectra have shown that the resulting samples have been related to the cellulose species. The thermal properties of CNCs have exhibited a lower thermal stability in comparison to the untreated roots. It has been indicated by the morphological analyses of FESEM, TEM, and AFM that the nanoparticles had contained a spherical shape. Also, the cytotoxicity of CNCs against A549 cell line has not exhibited any cytotoxic effects. The analysis of labeling efficiency in regards to 99mTc-CNCs has been observed to be above 98%, while the biodistribution of radioactivity has displayed a high uptake by the kidneys and blood circulation. Therefore, it is possible to transform the low-cost by-product into a beneficial substance such as CNCs that can be utilized in bioimaging applications.
Assuntos
Celulose , Nanopartículas , Raízes de Plantas/química , Tecnécio , Células A549 , Animais , Celulose/química , Celulose/farmacocinética , Celulose/farmacologia , Humanos , Masculino , Nanopartículas/química , Nanopartículas/uso terapêutico , Ratos , Ratos Wistar , Tecnécio/química , Tecnécio/farmacocinética , Tecnécio/farmacologia , Distribuição TecidualRESUMO
BACKGROUND: Clinically evident arterial thrombosis is rare following thrombin injection therapy for femoral pseudoaneurysm. However, it is unclear to what extent injected thrombin may pass to the ipsilateral lower limb arteries. AIMS: To assess if technetium 99m injected at the time of thrombin injection for femoral artery pseudoaneurysm therapy passes into the adjacent lower limb arteries. METHODS: This was a prospective trial with institutional review board approval. Four consecutive patients with common femoral pseudoaneurysms and failed manual compression were enrolled. Under real-time colour flow doppler ultrasound, a mixture of 1000 IU thrombin and approximately 200 MBq technetium 99m was injected in 0.1-mL doses into the pseudoaneurysm until thrombosis occurred. Gamma camera imaging of the syringe before injection, the injected groin after thrombosis and the syringe after injection were performed. Analysis of the gamma camera information was performed to determine the amount of technetium 99m deposited in the arterial tree. RESULTS: All the procedures were technically successful. A mean of 33% (range 3-50%; SD 21) of the administered technetium 99m dose was deposited in the arterial circulation during pseudoaneurysm therapy. No clinically evident arterial thrombosis was identified. CONCLUSION: Technetium 99m is routinely deposited in the arterial circulation following injection of a mixture of thrombin and technetium for therapy of common femoral artery pseudoaneurysms. This suggests that arterial passage of thrombin is more common than clinically evident.
Assuntos
Falso Aneurisma/tratamento farmacológico , Terapia Combinada/métodos , Embolia/tratamento farmacológico , Artéria Femoral/anormalidades , Cintilografia/métodos , Tecnécio/uso terapêutico , Trombina/uso terapêutico , Ultrassonografia de Intervenção/métodos , Idoso , Feminino , Humanos , Masculino , Estudos Prospectivos , Tecnécio/farmacologia , Trombina/farmacologiaRESUMO
Radiolabeling cidofovir with technetium-99m (99mTc-CDV) is an innovative procedure that enables real-time monitoring of the drug. Essays were performed in vitro, showing high radiolabel stability within 24 h. Blood clearance, biodistribution studies, and scintigraphic images were performed in healthy mice in order to evaluate the profile of the drug in vivo. 99mTc-CDV showed biphasic blood circulation time and significant kidney uptake, indicating that 99mTc-CDV is preferentially eliminated by the renal route. Bones also showed important uptake throughout the experiment. In summary, cidofovir was successfully labeled with technetium-99m and might be used in further studies to track the drug.
Assuntos
Animais , Masculino , Feminino , Camundongos , Técnicas In Vitro , Tecnécio/farmacologia , Cidofovir/farmacologia , Atletismo/classificação , Tempo de Circulação Sanguínea/efeitos adversos , Preparações Farmacêuticas/análise , Rim , MétodosRESUMO
Radioembolization treatment is preceded by a 99mTc-MAA safety procedure, which is used to estimate the lung shunt fraction (LSF). Normally, the LSF is estimated by using the geometric mean of planar scintigraphy (PS-GM). However, concern has been raised about the potential overestimation of the LSF by PS-GM. Alternatively, SPECT/CT may be used for LSF estimation, but requires lengthy acquisitions, 3D segmentation, and has a limited field of view, which calls for extrapolation of the reconstructed lung counts, which introduces another source of error. We have developed a simplified SPECT/CT protocol for LSF estimation, called the quantitative orthogonal planar (QOP) method that requires only four projections to quantitatively reconstruct liver and lung activity. This mitigates the problems associated with LSF estimations from SPECT/CT. The purpose of this study was to introduce and evaluate QOP by comparing its performance to PS-GM and SPECT/CT in a retrospective patient study, and by supporting simulation experiments. Patients who received at least one 99mTc-MAA safety procedure in our center were included in this study. QOP and PS-GM were compared to SPECT/CT in Bland-Altman analyses. Supporting digital phantom experiments with a known ground-truth were performed to evaluate the performance of this method. Analysis of PS-GM versus SPECT/CT LSF estimates revealed both a larger imprecision and significant bias by PS-GM (limits of agreement: 8.1 percentage points (pp); bias: 2.7 pp). The QOP method agreed better with the SPECT/CT-based estimation (limits of agreement: 2.07 pp; bias: 0.52 pp). This observation was consistent with the digital phantom experiments. We have proposed and evaluated a novel method called QOP for LSF estimation that performs almost as accurate as SPECT/CT, but without the need for lung mass extrapolation, long scan duration, or extensive manual segmentation, making it as fast as current PS-GM.
Assuntos
Embolização Terapêutica/métodos , Neoplasias Hepáticas/radioterapia , Pulmão/diagnóstico por imagem , Tomografia Computadorizada com Tomografia Computadorizada de Emissão de Fóton Único , Adulto , Idoso , Idoso de 80 Anos ou mais , Braquiterapia , Simulação por Computador , Embolização Terapêutica/efeitos adversos , Feminino , Humanos , Fígado/diagnóstico por imagem , Neoplasias Hepáticas/diagnóstico por imagem , Pulmão/efeitos da radiação , Masculino , Pessoa de Meia-Idade , Segurança do Paciente , Imagens de Fantasmas , Cintilografia , Reprodutibilidade dos Testes , Estudos Retrospectivos , Tecnécio/farmacologiaRESUMO
Development of tumor dual mode contrast agents is still a great challenge due to the relative low accumulation at tumor site, which result in the poor imaging efficiency. In this study, we constructed functional technetium-99m (99mTc) labeled polyethylenimine (PEI)-entrapped gold nanoparticles (Au PENs) with pH-responsive charge conversion property for enhanced single photon emission computed tomography (SPECT)/computed tomography (CT) dual mode imaging of cancer cells. PEI with amine functional groups (PEI.NH2) was successively modified with monomethyl ether and carboxyl functionalized polyethylene glycol (mPEG-COOH), maleimide and succinimidyl valerate functionalized PEG (MAL-PEG-SVA), diethylenetriaminepentaacetic dianhydride (DTPA), and fluorescein isothiocyanate (FI), and used to entrapped gold nanoparticles inside, followed by conjugation with the alkoxyphenyl acylsulfonamide (APAS) through the PEG maleimide, acetylation of the PEI leftover surface amines and 99mTc labeling. The created nanosystem with the mean Au core diameter of 3.3 nm and with a narrow size distribution displays an excellent colloidal stability and desired cytocompatibility in the investigated Au concentration range. Due to the fact that the attached APAS moieties are responsive to pH, the functionalized Au PENs with a neutral surface charge can switch to be positively charged under slightly acidic pH condition, which could improve the cellular uptake by cancer cells. With these properties, the developed functionalized Au PENs could achieve enhanced dual mode SPECT/CT imaging of cancer cells in vitro. The constructed PEI-based nanodevices may be adopted as an excellent dual mode contrast agent for SPECT/CT imaging of cancer cells of different types.
Assuntos
Ouro , Marcação por Isótopo , Nanopartículas Metálicas , Neoplasias , Polietilenoimina , Tomografia Computadorizada com Tomografia Computadorizada de Emissão de Fóton Único , Linhagem Celular Tumoral , Ouro/química , Ouro/farmacologia , Humanos , Concentração de Íons de Hidrogênio , Nanopartículas Metálicas/química , Nanopartículas Metálicas/uso terapêutico , Neoplasias/diagnóstico por imagem , Neoplasias/metabolismo , Polietilenoimina/química , Polietilenoimina/farmacologia , Tecnécio/química , Tecnécio/farmacologiaRESUMO
Here we reported the development of a novel immuno-SPECT tracer, namely 99mTc-JS001, to non-invasively image PD-1 expression in mice. The JS001 antibody was directly labeled by the most widely used SPECT radionuclide 99mTc with a radiochemical yield of 90%, and the specific activity was ≤74â¯GBq/mmol. After the radiolabeling, 99mTc-JS001 exhibited a similar immnuoaffinity to PD-1 in vitro. 99mTc-conjugated JS001 maintained intact in 5% HSA system for 24â¯h. S180 sarcoma xenograft-bearing Kunming mice and BGC823 gastric cancer orthotopic tumor model were built. Bio-distribution and/or immuno-SPECT studies with 99mTc-JS001 showed the antibody maintained in the blood, liver, kidneys and tumors at 1.5 ID%/g, 1.4 ID%/g, 2.0 ID%/g and 0.5 ID%/g, respectively. Also, there was a higher uptake in the BGC823 orthotopic tumor than that in the adjunct stomach. These results demonstrated that 99mTc-JS001 might have capacity to monitor the PD-1 expression in vivo, which might facilitate the anti-PD-1 antibodies treatment in preclinical models.
Assuntos
Anticorpos Monoclonais/uso terapêutico , Receptor de Morte Celular Programada 1/química , Tecnécio/uso terapêutico , Animais , Anticorpos Monoclonais/farmacologia , Humanos , Camundongos , Tecnécio/farmacologiaRESUMO
Endothelial dysfunction is a core pathophysiologic process in pulmonary arterial hypertension (PAH). We developed PulmoBind (PB), a novel imaging biomarker of the pulmonary vascular endothelium. 99mTechnetium (99mTc)-labelled PB binds to adrenomedullin receptors (AM1) densely expressed in the endothelium of alveolar capillaries. We evaluated the effect of sildenafil on AM1 receptors activity using 99mTc-PB. PAH was induced in rats using the Sugen/hypoxia model and after 3 weeks, animals were allocated to sildenafil (25 or 100 mg/kg/day) for 4 weeks. 99mTc-PB uptake kinetics was assessed by single-photon emission computed tomography. PAH caused right ventricular (RV) hypertrophy that was decreased by low and high sildenafil doses. Sildenafil low and high dose also improved RV function measured from the tricuspid annulus plane systolic excursion. Mean integrated pulmonary uptake of 99mTc-PB was reduced in PAH (508% · min ± 37, p < 0.05) compared to controls (630% · min ± 30), but unchanged by sildenafil at low and high doses. Lung tissue expressions of the AM1 receptor components were reduced in PAH and also unaffected by sildenafil. In experimental angio-proliferative PAH, sildenafil improves RV dysfunction and remodeling, but does not modify pulmonary vascular endothelium dysfunction assessed by the adrenomedullin receptor ligand 99mTc-PB.