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1.
Medicine (Baltimore) ; 99(4): e18905, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31977903

RESUMO

Although pathological confirmation is the gold standard for diagnosis of amyloidosis, there is a need for a relevant imaging modality to identify involved organs and evaluate disease extent. Thus, we prospectively investigated imaging findings of Tc-DPD scintigraphy in AL and ATTR amyloidosis.A total of 21 subjects with pathologically confirmed AL or ATTR amyloidosis were included. Pretreatment whole body Tc-DPD planar scanning and regional SPECT/CT were performed in all subjects. For allegedly involved organs, Tc-DPD uptake was visually and semi-quantitatively evaluated on a 4-point scale (grade 0: no uptake, 1: uptake less than spine, 2: uptake similar to spine, and 3: uptake greater than spine).There were 29 organs involved in AL and 12 in ATTR. Significant Tc-DPD uptake was found in 24 organs (sensitivity = 82.8%) in AL and 9 organs (sensitivity = 75.0%) in ATTR. Additional SPECT/CT was helpful to ensure abnormal DPD uptake in the involved organs, which was uncertain by attenuation in planar imaging. Degree of Tc-DPD uptake was significantly higher in ATTR compared with AL amyloidosis (P = .017). Diffuse soft tissue uptake with photon defects in the liver area was found only in ATTR amyloidosis.This study showed that Tc-DPD scintigraphy might have capacity to differentiate between AL and ATTR subtypes with good sensitivity in various organs involving primary systemic AL and ATTR amyloidosis. Additional SPECT/CT significantly improved the diagnostic efficacy of Tc-DPD scintigraphy.


Assuntos
Neuropatias Amiloides Familiares/diagnóstico por imagem , Amiloidose de Cadeia Leve de Imunoglobulina/diagnóstico , Cintilografia/métodos , Tomografia Computadorizada com Tomografia Computadorizada de Emissão de Fóton Único/métodos , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Compostos de Organotecnécio/administração & dosagem , Imagem Corporal Total
2.
Medicine (Baltimore) ; 98(46): e16525, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31725599

RESUMO

To evaluate the clinical value of NeuroGam software in assessing the brain foci perfusion changes by TC-ECD single photon emission computed tomography/computed tomography (SPECT/CT) brain imaging in patients with Moyamoya Disease (MMD).Seventy-two patients with MMD who underwent superficial temporal artery-middle cerebral artery (STA-MCA) bypass combined with encephalo-duro-myo-synangiosis (EDMS) surgical revascularization were included. Baseline and follow-up TC-ECD SPECT/CT brain scans were performed on all patients at least twice before and after operation. Pre- and post-SPECT dicom images were reoriented into Talairach space using NeuroGam Software package. Additional visual analysis was performed. Differences mean pixel value between pre- and post- operation brain perfusion were assessed with paired t test and McNemar test.Significant differences in the number of hypoperfusion foci were found between visual assessment and NeuroGam aided assessment. More hypoperfusion foci were found by NeuroGam software aided assessment in the frontal, parietal, temporal, occipital lobe, thalamus, basal ganglia and cerebellum before and after surgery (P < .0001). According to NeuroGam software assessment, the perfusion of frontal, parietal, temporal lobe, anterior and middle cerebral regions on the operative side significantly improved before and after surgery (t = -3.734, t = -3.935, t = -5.099, t = -4.006, t = -5.170, all P < .001). However, no significant differences were found in the occipital lobe (t = -1.962, P = .054), thalamus (t = 1.362, P = .177), basal ganglia (t = -2.394, P = .019), and cerebellum (t = 1.383, P = .171) before and after surgery.The NeuroGam software provides a quantitative approach for monitoring surgical effect of MMD in a variable time (3-12 months after surgery). It could discover the perfusion changes that are neglected in conventional visual assessment.


Assuntos
Cisteína/análogos & derivados , Interpretação de Imagem Assistida por Computador/métodos , Doença de Moyamoya/diagnóstico por imagem , Compostos de Organotecnécio , Compostos Radiofarmacêuticos , Tomografia Computadorizada com Tomografia Computadorizada de Emissão de Fóton Único/estatística & dados numéricos , Adolescente , Adulto , Encéfalo/diagnóstico por imagem , Encéfalo/cirurgia , Revascularização Cerebral/métodos , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Artéria Cerebral Média/cirurgia , Doença de Moyamoya/cirurgia , Período Pós-Operatório , Período Pré-Operatório , Tomografia Computadorizada com Tomografia Computadorizada de Emissão de Fóton Único/métodos , Software , Artérias Temporais/cirurgia , Resultado do Tratamento , Adulto Jovem
3.
Medicine (Baltimore) ; 98(38): e17256, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31567998

RESUMO

RATIONALE: Cardiac amyloidosis, considered for the last years to be a rare disease, is one of the determinants of HFpEF. The non-specific clinical presentation and the difficulties related to endomyocardial biopsy have made cardiac amyloidosis an underdiagnosed clinical entity. Improvement of non-invasive diagnostic techniques and the development of new therapies increased clinical awareness for this form of restrictive cardiomyopathy. We here summarize echocardiography and Tc-HDP scintigraphy findings in 6 cases of cardiac amyloidosis and review the literature data of this progressive and fatal cardiomyopathy. PATIENTS CONCERNS: The main clinical manifestations were fatigue, low exercise tolerance and edemas. The right heart failure symptoms usually dominated the clinical picture. DIAGNOSES: All cases were evaluated by echocardiography; 3 cases were further examined by bone scintigraphy and 4 cases a peripheral biopsy was performed. Electrocardiography showed low-voltage QRS complexes and "pseudo-infarct" pattern in the precordial leads, contrary to the echocardiographic aspect, which revealed thickening of ventricle walls. Biatrial dilation and diastolic disfunction were observed. Impaired systolic function was detected in advanced stages of the disease. Tc-HDP scintigraphy revealed cardiac uptake of radiopharmaceutical and managed to confirm the diagnosis in 1 case of cardiac amyloidosis in which salivary gland biopsy was negative. INTERVENTIONS: The treatment was based on managing fluid balance, with the mainstream therapy represented by diuretics. Neurohormonal agents, usually used in heart failure treatment were avoided, due to poor tolerance and worsening of disease course. The management of these 6 cases was challenging due to the refractory manifestation of congestive heart failure. OUTCOMES: During follow-up, 4 of the 6 patients from the current study died in the first year after the final diagnosis was established. LESSONS: Nuclear imaging of cardiac amyloidosis has a revolutionary development nowadays. Bone scintigraphy presents promising results for identifying patients at early stages of disease and to differentiate between cardiac amyloidosis types. Further studies are necessary for the standardization of imaging protocol and development of non-invasive diagnostic tools, especially in assessing the response to treatment and disease progression, for which little is known.


Assuntos
Amiloidose/diagnóstico por imagem , Ecocardiografia , Cardiopatias/diagnóstico por imagem , Cintilografia/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Amiloidose/diagnóstico , Amiloidose/patologia , Difosfonatos , Feminino , Coração/diagnóstico por imagem , Cardiopatias/diagnóstico , Cardiopatias/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Miocárdio/patologia , Compostos de Organotecnécio
4.
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
5.
Clin Nucl Med ; 44(8): 650-652, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31274613

RESUMO

A 77-year-old man with a history of metastatic Merkel cell carcinoma and debilitating painful cutaneous lesions was referred to our nuclear medicine department for peptide receptor radionuclide therapy with Lu-DOTATATE as ultimate therapeutic option. Post-treatment whole body scan showed multiple zones of Lu-DOTATATE uptake in the metastatic regions, which revealed significant improvement within the next 10 days of therapy. Peptide receptor radionuclide therapy in metastatic Merkel cell carcinoma is an effective therapeutic option that should be considered in earlier stages of the disease.


Assuntos
Carcinoma de Célula de Merkel/radioterapia , Tumores Neuroendócrinos/radioterapia , Idoso , Carcinoma de Célula de Merkel/diagnóstico por imagem , Carcinoma de Célula de Merkel/patologia , Humanos , Masculino , Metástase Neoplásica , Tumores Neuroendócrinos/diagnóstico por imagem , Tumores Neuroendócrinos/patologia , Octreotida/análogos & derivados , Octreotida/uso terapêutico , Compostos Organometálicos/uso terapêutico , Compostos de Organotecnécio , Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos/uso terapêutico , Imagem Corporal Total
6.
Clin Nucl Med ; 44(10): 834-835, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31306209

RESUMO

A 63-year-old woman with neuroendocrine carcinoma of the colon was referred to our department for staging with Tc-octreotide scan. Two focal, highly intense, superficial lesions were detected in patient's scalp and paralumbar region, medial to the right kidney. Pathology correlation was recommended, revealing them both to be benign trichilemmal cysts. This unexpected finding strengthens the hypothesis of Merkel cell carcinoma and trichilemmal cysts originating from pluripotent stem cells of adnexal epithelium, making a neuroendocrine differentiation for the latter plausible.


Assuntos
Cisto Epidérmico/diagnóstico por imagem , Achados Incidentais , Octreotida/análogos & derivados , Compostos de Organotecnécio , Carcinoma Neuroendócrino/complicações , Carcinoma Neuroendócrino/diagnóstico por imagem , Carcinoma Neuroendócrino/patologia , Cisto Epidérmico/complicações , Feminino , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias
7.
Eur J Med Chem ; 177: 291-301, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31158745

RESUMO

Based on our previous research on the fluorinated phenylquinoxaline scaffold, in this study, different positions of N,N-dimethyl amino group, and alkyl linkers with various lengths were introduced into this scaffold to regulate their lipophilicity and binding affinity to Tau. Four novel 99mTc/Re complexes with diethyl iminodiacetate chelator were synthesized and evaluated as Tau imaging tracers in the brain of Alzheimer's disease. Their specific binding to neurofibrillary tangles was verified by in vitro fluorescence staining and further confirmed by the results of immunofluorescence staining on the same brain sections from AD patient and Tg-tau mice. From in vitro binding assay using recombinant Tau aggregates, complex 4.2 with 6-N(CH3)2 and longer carbon chain (n = 4) displayed the highest affinity (Kd = 59.95 nM). [99mTc]4.2 was achieved by the ligand exchange reaction between dicarboxylic precursor and [99mTc(CO)3(H2O)3]+ intermediate with radiochemical yield over 45%. Ex vivo biodistribution studies on normal ICR mice revealed that [99mTc]4.2 exhibited moderate initial brain uptake (0.61% ID/g) and more structure optimizations are still required to improve the blood-brain barrier permeability.


Assuntos
Doença de Alzheimer/diagnóstico , Complexos de Coordenação/química , Corantes Fluorescentes/química , Compostos de Organotecnécio/química , Quinoxalinas/química , Proteínas tau/metabolismo , Idoso de 80 Anos ou mais , Peptídeos beta-Amiloides/metabolismo , Animais , Barreira Hematoencefálica/metabolismo , Encéfalo/metabolismo , Encéfalo/patologia , Quelantes/síntese química , Quelantes/química , Quelantes/metabolismo , Complexos de Coordenação/síntese química , Complexos de Coordenação/metabolismo , Feminino , Fluorescência , Corantes Fluorescentes/síntese química , Corantes Fluorescentes/metabolismo , Humanos , Iminoácidos/síntese química , Iminoácidos/química , Iminoácidos/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos ICR , Estrutura Molecular , Emaranhados Neurofibrilares/metabolismo , Emaranhados Neurofibrilares/patologia , Compostos de Organotecnécio/síntese química , Compostos de Organotecnécio/metabolismo , Fragmentos de Peptídeos/metabolismo , Quinoxalinas/síntese química , Quinoxalinas/metabolismo , Compostos Radiofarmacêuticos/síntese química , Compostos Radiofarmacêuticos/química , Compostos Radiofarmacêuticos/metabolismo , Rênio/química , Distribuição Tecidual
8.
Mater Sci Eng C Mater Biol Appl ; 102: 124-133, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31146983

RESUMO

Novel theranostic nanoplatform is expected to integrate imaging for guiding and monitoring of the tumor therapy with great therapeutic efficacy and fewer side effects. Here we describe the preparation of a multifunctional 99mTc-bisphosphonate-coated magnetic nanoparticles (MNPs) based on Fe3O4 and coated with two hydrophilic bisphosphonate ligands, i.e., methylene diphosphonate (MDP) and 1-hydroxyethane-1,1- diphosphonate (HEDP). The presence of the bisphosphonates on the MNPs surface, enabled their biocompatibility, colloidal stability and successful binding of the radionuclide. The morphology, size, structure, surface charge and magnetic properties of obtained bisphosphonate-coated Fe3O4 MNPs were characterized by transmission electron microscopy, X-ray powder diffraction, dynamic light scattering, laser Doppler electrophoresis, Fourier transform infrared spectroscopy and vibrating sample magnetometer. The specific power absorption values for Fe3O4-MDP and Fe3O4-HEDP were 113 W/g and 141 W/g, respectively, indicated their heating ability under applied magnetic field. Coated MNPs were radiolabeled with 99mTc using stannous chloride as the reducing agent in a reproducible high yield (95% for Fe3O4-MDP and 97% for Fe3O4-HEDP MNPs) and were remained stable in saline and human serum for 24 h. Ex vivo biodistribution studies presented significant liver and spleen uptake in healthy Wistar rats after intravenous administration at all examined time points due to the colloidal nature of both 99mTc-MNPs. Results of scintigraphy studies are in accordance with ex vivo biodistribution studies, demonstrating high in vivo stability of radiolabeled MNPs and therefore results of both methods were proved as accurate information on the biodistribution profile of investigated MNPs. Overall, in vitro and in vivo stability as well as heating ability, indicate that biocompatible radiolabeled bisphosphonate magnetic nanoparticles exhibit promising potential as a theranostic nanoagent.


Assuntos
Materiais Revestidos Biocompatíveis/química , Difosfonatos/química , Nanopartículas de Magnetita/química , Compostos de Organotecnécio/química , Nanomedicina Teranóstica , Animais , Hipertermia Induzida , Nanopartículas de Magnetita/ultraestrutura , Masculino , Tamanho da Partícula , Ratos Wistar , Temperatura Ambiente , Fatores de Tempo , Distribuição Tecidual , Difração de Raios X
9.
Molecules ; 24(12)2019 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-31248199

RESUMO

Hyperlipidemia causes systemic lipid disorder, which leads to hepatic steatosis and atherosclerosis. Thus, it is necessary to detect these syndromes early and precisely to improve prognosis. In the affected regions, abnormal formation and growth of lipid droplets is observed; therefore, lipid droplets may be a suitable target for the diagnosis of hyperlipidemia-related syndromes. In this study, we designed and synthesized [99mTc]Tc-BOD and [99mTc]Tc-MBOD composed of one technetium-99m and two BODIPY scaffolds with hydroxamamide (Ham) or N-methylated hydroxamamide (MHam) in radiochemical yields of 54 and 35%, respectively, with a radiochemical purity of over 95%. [99mTc]Tc-BOD showed significantly higher accumulation levels in foam cells than in non-foam cells (foam cells: 213.8 ± 64.8, non-foam cell: 126.2 ± 26.9 %dose/mg protein, p < 0.05) 2 h after incubation. In contrast, [99mTc]Tc-MBOD showed similar accumulation levels in foam cells and non-foam cells (foam cells: 92.2 ± 23.3, non-foam cell: 83.8 ± 19.8 %dose/mg protein). In normal mice, [99mTc]Tc-BOD exhibited gradual blood clearance (0.5 h: 4.98 ± 0.35, 6 h: 1.94 ± 0.12 %ID/g) and relatively high accumulation in the liver 6 h after administration (15.22 ± 1.72 %ID/g). Therefore, [99mTc]Tc-BOD may have potential as an imaging probe for detecting lipid droplets in disease lesions of hyperlipidemia.


Assuntos
Amidas , Hiperlipidemias/diagnóstico , Hiperlipidemias/metabolismo , Sondas Moleculares , Compostos de Organotecnécio , Compostos Radiofarmacêuticos , Amidas/química , Animais , Estabilidade de Medicamentos , Humanos , Marcação por Isótopo , Gotículas Lipídicas/metabolismo , Camundongos , Compostos de Organotecnécio/química , Compostos Radiofarmacêuticos/síntese química , Compostos Radiofarmacêuticos/química , Compostos Radiofarmacêuticos/farmacocinética , Distribuição Tecidual
10.
Clin Nucl Med ; 44(10): e590-e592, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31058689

RESUMO

Tc-TRODAT-1, as a tropane-derived compound with highly selective binding to the dopamine transporter, has been extensively used as an in vivo biomarker to evaluate parkinsonism. There have been few reports indicating various etiologies about extrastriatal findings on the Tc-TRODAT-1 SPECT. We herein present an interesting case about the incidental discovery of brain lymphoma with increasing uptake of Tc-TRODAT-1.


Assuntos
Encéfalo/diagnóstico por imagem , Linfoma/diagnóstico por imagem , Compostos de Organotecnécio , Tomografia Computadorizada de Emissão de Fóton Único , Tropanos , Transporte Biológico , Encéfalo/metabolismo , Feminino , Humanos , Achados Incidentais , Linfoma/metabolismo , Pessoa de Meia-Idade , Compostos de Organotecnécio/metabolismo , Tropanos/metabolismo
11.
Technol Cancer Res Treat ; 18: 1533033819842586, 2019 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31079574

RESUMO

BACKGROUND: Νeuroendocrine tumors of the lungs are rare arising in the thymus and gastro-entero-pancreatic tract and belonging to foregut of neuroendocrine tumors. The aim of the present prospective study was to estimate the potential impact of single-photon emission computed tomography somatostatin receptor scintigraphy using 99mTc-Tektrotyd on diagnosis, treatment response, and prognosis in patients with neuroendocrine tumors of the lungs. METHODS: Thirty-six patients with neuroendocrine tumors of the lungs were evaluated by using 99mTc-HYNIC-TOC scintigraphy. The scintigraphic results were compared to liver tissue uptake (Krenning score). Likewise, the functional imaging results were compared with biochemical indices including chromogranin A, neuroendocrine-specific enolase, and insulin-like growth factor 1 at the time of diagnosis (baseline) and disease progression. RESULTS: The number of somatostatin receptors, expressed with Krenning score, did not show any correlation with the survival of patients both at baseline ( P = .08) and at disease progression ( P = .24), and scintigraphy results did not relate significantly to progression-free survival. Comparing the results of 99mTc-HYNIC-TOC scintigraphy according to the response of patients in the initial treatment, a statistically significant negative correlation was observed both in the first and in the second scintigraphy with patients' response ( P = .001 and P < .001, respectively). The concentrations of biochemical markers were in accordance with scintigraphy results in the diagnosis. CONCLUSION: This study indicates that 99mTc-HYNIC-TOC scintigraphy appears to be a reliable, noninvasive technique for detection of primary neuroendocrine tumors and their locoregional or distant metastases, although it cannot be used as a neuroendocrine tumors of the lungs predictive technique.


Assuntos
Neoplasias Pulmonares/diagnóstico , Tumores Neuroendócrinos/diagnóstico , Octreotida/análogos & derivados , Compostos de Organotecnécio , Cintilografia , Idoso , Biomarcadores Tumorais , Progressão da Doença , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/terapia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Tumores Neuroendócrinos/sangue , Tumores Neuroendócrinos/mortalidade , Tumores Neuroendócrinos/terapia , Valor Preditivo dos Testes , Cintilografia/métodos , Resultado do Tratamento
12.
Ann Nucl Med ; 33(8): 606-616, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31134434

RESUMO

OBJECTIVE: Folate receptor (FR) is an ideal target for cancer imaging because it is frequently overexpressed in major types of human tumor, whereas its expression in normal organs is highly limited. Combining nuclear and fluorescence-imaging techniques provides a novel approach for cancer imaging and monitoring the surgery. The objective of this study was to report the synthesis and characteristics of a dual-modality imaging agent, Tc-99m Folate-Gly-His-Glu-Gly-Glu-Cys-Gly-Lys(-5-carboxy-X-rhodamine)-NH2 (Folate-ECG-ROX), and verify its feasibility as both molecular imaging agent and intra-operative guidance. METHODS: Folate-ECG-ROX was synthesized using Fmoc solid-phase peptide synthesis. Radiolabeling of Folate-ECG-ROX with Tc-99m was done using ligand exchange via tartrate. Binding affinity and in vitro cellular uptake studies were performed. Gamma camera imaging, biodistribution and ex vivo imaging studies were performed using KB and HT-1080 tumor-bearing murine models. Tumor tissue slides were prepared and analyzed with immunohistochemistry staining and confocal microscopy. Surgical removal of tumor nodules in murine models with peritoneal carcinomatosis was performed under the fluorescence-imaging system. RESULTS: After radiolabeling procedures with Tc-99m, Tc-99m Folate-ECG-ROX complexes were prepared in high yield (> 97%). The binding affinity value (Kd) of Tc-99m Folate-ECG-ROX for KB cells was estimated to be 6.9 ± 0.9 nM. In gamma camera imaging, tumor to normal muscle uptake ratio of Tc-99m Folate-ECG-ROX increased with time (3.4 ± 0.4, 4.4 ± 0.7, and 6.6 ± 0.8 at 1, 2, and 3 h, respectively). In biodistribution study, %IA/g for KB tumor was 2.50 ± 0.80 and 4.08 ± 1.16 at 1 and 3 h, respectively. Confocal microscopy with immunohistochemistry staining detected strong Tc-99m Folate-ECG-ROX fluorescence within KB tumor tissue which is correlating with the fluorescent activity of anti-FR antibody. Under real-time optical imaging, the removal of visible nodules was successfully performed. CONCLUSIONS: In vivo and in vitro studies revealed substantial and specific uptake of Tc-99m Folate-ECG-ROX in FR-positive tumors. Thus, Tc-99m Folate-ECG-ROX could provide both pre-operative molecular imaging and fluorescence image-guidance for tumor.


Assuntos
Receptores de Folato com Âncoras de GPI/metabolismo , Ácido Fólico/química , Ácido Fólico/metabolismo , Imagem Óptica/métodos , Neoplasias Peritoneais/diagnóstico por imagem , Neoplasias Peritoneais/cirurgia , Cirurgia Assistida por Computador , Animais , Transporte Biológico , Transformação Celular Neoplásica , Estudos de Viabilidade , Feminino , Ácido Fólico/farmacocinética , Humanos , Marcação por Isótopo , Células KB , Camundongos , Compostos de Organotecnécio/química , Distribuição Tecidual
13.
Eur J Med Chem ; 175: 149-161, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31078865

RESUMO

Six novel 2-arylimidazo[2,1-b]benzothiazole (IBT) derivatives were synthesized as potential tridentate radiotracers for AD imaging purposes. Two of these ligands (6a,b) were successfully labeled with 99mTc radionuclide at high radiochemical purity using fac-[99mTc(CO)3(H2O)3]+ synthon. [99mTc]7a and [99mTc]7b were evaluated as single photon emission computed tomography (SPECT) imaging agents for Aß plaque in AD. [99mTc]7a and [99mTc]7b exhibited suitable affinity toward Aß aggregates with IC50 values of 33.2 and 102.5 nM, respectively. The IC50 value of these radiotracers depends on the length of the spacer (alkyl chain). In biodistribution study, these complexes showed good initial brain uptakes (0.78 and 0.86% ID/g at 2 min post-injection) and fast blood clearance. Autoradiography results confirmed that these small 99mTc complexes (Mw about 600 Da) can bind to Aß plaques in the brain sections of the rat AD model. Histopathological staining with Congo red approved the presence of Aß plaques in these brain sections.


Assuntos
Doença de Alzheimer/diagnóstico por imagem , Benzotiazóis/metabolismo , Imidazóis/química , Compostos de Organotecnécio/metabolismo , Placa Amiloide/diagnóstico por imagem , Compostos Radiofarmacêuticos/metabolismo , Tomografia Computadorizada de Emissão de Fóton Único/métodos , Doença de Alzheimer/metabolismo , Animais , Benzotiazóis/química , Benzotiazóis/farmacocinética , Barreira Hematoencefálica , Encéfalo/metabolismo , Modelos Animais de Doenças , Camundongos , Compostos de Organotecnécio/farmacocinética , Compostos Radiofarmacêuticos/farmacocinética , Ratos , Distribuição Tecidual
14.
Med Biol Eng Comput ; 57(7): 1581-1590, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31025249

RESUMO

The accuracy of recently approved quantitative clinical software was determined by comparing in vivo/in vitro measurements for a solid-state cadmium-zinc-telluride SPECT/CT (single photon emission computed tomography/x-ray computed tomography) camera. Bone SPECT/CT, including the pelvic region in the field of view, was performed on 16 patients using technetium-99m methylene diphosphonic acid as a radiotracer. After imaging, urine samples from each patient provided for the measurement of in vitro radiopharmaceutical concentrations. From the SPECT/CT images, three users measured in vivo radiotracer concentration and standardized uptake value (SUV) for the bladder using quantitative software (Q.Metrix, GE Healthcare). Linear regression was used to validate any in vivo/in vitro identity relations (ideally slope = 1, intercept = 0), within a 95% confidence interval (CI). Thirteen in vivo/in vitro pairs were available for further analysis, after rejecting two as clinically irrelevant (SUVs > 100 g/mL) and one as an outlier (via Cook's distance calculations). All linear regressions (R2 ≥ 0.85, P < 0.0001) provided identity in vivo/in vitro relations (95% CI), with SUV averages from all users giving a slope of 0.99 ± 0.25 and intercept of 0.14 ± 5.15 g/mL. The average in vivo/in vitro residual difference was < 20%. Solid-state SPECT/CT imaging can reliably provide in vivo urinary bladder radiotracer concentrations within approximately 20% accuracy. This practical, non-invasive, in vivo quantitation method can potentially improve diagnosis and assessment of response to treatment. Graphical abstract.


Assuntos
Processamento de Imagem Assistida por Computador/métodos , Cintilografia/métodos , Compostos Radiofarmacêuticos/análise , Software , Tomografia Computadorizada de Emissão de Fóton Único/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Cádmio , Calibragem , Difosfonatos/administração & dosagem , Difosfonatos/análise , Difosfonatos/urina , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Compostos de Organotecnécio/administração & dosagem , Compostos de Organotecnécio/análise , Compostos de Organotecnécio/urina , Imagens de Fantasmas , Compostos Radiofarmacêuticos/administração & dosagem , Compostos Radiofarmacêuticos/urina , Telúrio , Tomografia Computadorizada de Emissão de Fóton Único/instrumentação , Bexiga Urinária/diagnóstico por imagem , Imagem Corporal Total/métodos , Zinco
15.
Int Heart J ; 60(3): 643-647, 2019 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-31019172

RESUMO

Senile or wild-type transthyretin (wtTTR) amyloidosis is an age-related disease caused by the deposition of wtTTR amyloid protein. In contrast to light chain amyloidosis, 99 mTc-DPD scintigraphy (DPD scan) is a useful diagnostic modality for wtTTR amyloidosis.We retrospectively analyzed patients older than 30 years who underwent DPD scanning for non-cardiac reasons at our hospital between June 2014 and March 2017 (n = 9,581). Transthoracic echocardiography was used to assess left ventricular hypertrophy (LVH), as well as systolic and diastolic function.A positive DPD scan was observed in only six patients (0.06%). All six of these patients were older than 70 years, and they constitute only 0.4% of patients in this age group (6/1652). Among the patients with a positive DPD scan, four showed concentric LVH and two showed a normal wall thickness. With respect to the severity of diastolic dysfunction and pulmonary artery pressure, patients with a positive DPD scan showed the expected E' and pulmonary artery systolic pressure for their age.Even considering the limited sensitivity of a positive DPD scan detecting wtTTR amyloidosis, the incidence of a positive DPD scan in non-cardiac patients indicated that wtTTR amyloid deposition does not seem to be a major cause for age-related diastolic dysfunction, nor does appear to have a high incidence in patients with heart failure with preserved EF in the elderly.


Assuntos
Neuropatias Amiloides Familiares/diagnóstico , Neuropatias Amiloides Familiares/epidemiologia , Hipertrofia Ventricular Esquerda/diagnóstico por imagem , Compostos de Organotecnécio/metabolismo , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Neuropatias Amiloides Familiares/genética , Neuropatias Amiloides Familiares/metabolismo , Ecocardiografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pré-Albumina/genética , Prevalência , Estudos Retrospectivos , Sensibilidade e Especificidade
16.
Sensors (Basel) ; 19(7)2019 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-30978990

RESUMO

The neuroimaging techniques such as dopaminergic imaging using Single Photon Emission Computed Tomography (SPECT) with 99mTc-TRODAT-1 have been employed to detect the stages of Parkinson's disease (PD). In this retrospective study, a total of 202 99mTc-TRODAT-1 SPECT imaging were collected. All of the PD patient cases were separated into mild (HYS Stage 1 to Stage 3) and severe (HYS Stage 4 and Stage 5) PD, according to the Hoehn and Yahr Scale (HYS) standard. A three-dimensional method was used to estimate six features of activity distribution and striatal activity volume in the images. These features were skewness, kurtosis, Cyhelsky's skewness coefficient, Pearson's median skewness, dopamine transporter activity volume, and dopamine transporter activity maximum. Finally, the data were modeled using logistic regression (LR) and support vector machine (SVM) for PD classification. The results showed that SVM classifier method produced a higher accuracy than LR. The sensitivity, specificity, PPV, NPV, accuracy, and AUC with SVM method were 0.82, 1.00, 0.84, 0.67, 0.83, and 0.85, respectively. Additionally, the Kappa value was shown to reach 0.68. This claimed that the SVM-based model could provide further reference for PD stage classification in medical diagnosis. In the future, more healthy cases will be expected to clarify the false positive rate in this classification model.


Assuntos
Corpo Estriado/diagnóstico por imagem , Doença de Parkinson/diagnóstico por imagem , Máquina de Vetores de Suporte , Tomografia Computadorizada de Emissão de Fóton Único , Adulto , Idoso , Idoso de 80 Anos ou mais , Corpo Estriado/efeitos dos fármacos , Corpo Estriado/patologia , Dopamina/química , Dopamina/metabolismo , Proteínas da Membrana Plasmática de Transporte de Dopamina/química , Proteínas da Membrana Plasmática de Transporte de Dopamina/metabolismo , Neurônios Dopaminérgicos/efeitos dos fármacos , Neurônios Dopaminérgicos/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Compostos de Organotecnécio/administração & dosagem , Doença de Parkinson/classificação , Doença de Parkinson/diagnóstico , Doença de Parkinson/patologia , Estudos Retrospectivos , Tropanos/administração & dosagem
17.
Colloids Surf B Biointerfaces ; 179: 143-152, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-30954015

RESUMO

The imaging of healthy tissues and solid tumors benefits from the application of nanoparticle probes with altered pharmacokinetics, not available to low molecular weight compounds. However, the distribution and accumulation of nanoprobes in vivo typically take at least tens of hours to be efficient. For nanoprobes bearing a radioactive label, this is contradictory to the requirement of minimizing the radiation dose for patients by using as-short-as-feasible half-life radionuclides in diagnostics. Thus, we developed a two-stage diagnostic concept for monitoring long-lasting targeting effects with short-lived radioactive labels using bone-mimicking biocompatible polymer-coated and colloidally fully stabilized hydroxyapatite nanoparticles (HAP NPs) and bone-seeking radiopharmaceuticals. Within the pretargeting stage, the nonlabeled nanoparticles are allowed to circulate in the blood. Afterward, 99mTc-1-hydroxyethylidene-1.1-diphosphonate (99mTc-HEDP) is administered intravenously for in situ labeling of the nanoparticles and subsequent single-photon emission computed tomography/computed tomography (SPECT/CT) visualization. The HAP NPs, stabilized with tailored hydrophilic polymers, are not cytotoxic in vitro, as shown by several cell lines. The polymer coating prolongs the circulation of HAP NPs in the blood. The nanoparticles were successfully labeled in vivo with 99mTc-HEDP, 1 and 24 h after injection, and they were visualized by SPECT/CT over time in healthy mice.


Assuntos
Durapatita/química , Nanopartículas/química , Polímeros/química , Compostos Radiofarmacêuticos/química , Animais , Linhagem Celular Tumoral , Endocitose , Fluoresceína/química , Corantes Fluorescentes/química , Humanos , Imagem Tridimensional , Camundongos Endogâmicos BALB C , Nanopartículas/ultraestrutura , Compostos de Organotecnécio/química , Espectroscopia de Prótons por Ressonância Magnética , Distribuição Tecidual , Tomografia Computadorizada de Emissão de Fóton Único , Tomografia Computadorizada por Raios X
18.
BMJ Case Rep ; 12(4)2019 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-30940668

RESUMO

There is literature evidence showing utility of somatostatin receptor (SSTR) positron emission tomography-CT (PET-CT) imaging in differentiated thyroid cancer with Thyroglobulin Elevated and Negative Iodine Scan (TENIS). These patients are less benefited with I-131 therapy and surgery remains only curable option if disease could be localised. If surgery is not feasible, other therapeutic options are not promising. However, if these patients show strongly positive SSTR imaging, then possibility of peptide receptor radionuclide therapy may be explored. As SSTR PET-CT imaging is expensive and not widely available, Technetium-99m (Tc-99m) hydrazinonicotinyl-Tyr3-octreotide (HYNIC-TOC), which is a Single photon emission computed tomography (SPECT) tracer, can be used. We are documenting a case of raised serum thyroglobulin antibody and negative I-131 whole body scan with disease recurrence localised on Tc-99m HYNIC-TOC scan.


Assuntos
Recidiva Local de Neoplasia/diagnóstico por imagem , Octreotida/análogos & derivados , Compostos de Organotecnécio , Câncer Papilífero da Tireoide/diagnóstico por imagem , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Imagem Corporal Total , Idoso , Feminino , Humanos , Radioisótopos do Iodo , Octreotida/administração & dosagem , Octreotida/farmacologia , Compostos de Organotecnécio/administração & dosagem , Compostos de Organotecnécio/farmacologia , Câncer Papilífero da Tireoide/terapia , Neoplasias da Glândula Tireoide/terapia
19.
J BUON ; 24(1): 347-353, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30941991

RESUMO

PURPOSE: This study compared the potential of 2 nanoparticles, namely albumin and gold nanoparticles, for the specific delivery of 99mTC- resveratrol in colon cancer. The aim of adding radioactive tag (99mTC) to resveratrol was to utilize it for imaging purposes. METHODS: We compared the potential of albumin loaded 99mTC- resveratrol with gold nanoparticles loaded 99mTc-resveratrol for tumor specific delivery. Twenty male Wistar rats were used for the formation of colon cancer model. Both delivery molecules were tested for tumor specific delivery. RESULTS: The results showed efficient delivery of 99mTC-resveratrol with albumin in comparison to gold nanoparticles, as confirmed by single-photon emission computed tomography (SPECT). CONCLUSIONS: Albumin is a superior molecule for the efficient delivery of 99mTC- resveratrol at tumor sites in comparison to gold nanoparticles.


Assuntos
Albuminas/administração & dosagem , Albuminas/química , Antineoplásicos/administração & dosagem , Antineoplásicos/química , Neoplasias do Colo/tratamento farmacológico , Nanopartículas Metálicas/administração & dosagem , Nanopartículas Metálicas/química , Animais , Neoplasias do Colo/metabolismo , Neoplasias do Colo/patologia , Ouro/administração & dosagem , Ouro/química , Humanos , Masculino , Compostos de Organotecnécio/administração & dosagem , Compostos de Organotecnécio/química , Compostos Radiofarmacêuticos/administração & dosagem , Compostos Radiofarmacêuticos/química , Distribuição Aleatória , Ratos , Ratos Wistar , Resveratrol/administração & dosagem , Resveratrol/farmacocinética
20.
Biomater Sci ; 7(5): 2061-2075, 2019 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-30855618

RESUMO

For clinical application of therapeutic gene delivery, it is urgent to develop safe and in vivo efficient delivery systems. Nowadays, gene delivery carriers based on functional peptides have attracted much attention due to their excellent biocompatibility, biodegradability and biological multifunctionality. In the present study, a star-shaped integrated functional peptide, polyhedral oligomeric silsesquioxane (POSS-(C-G-NLS-G-TAT)16, abbreviated as PP1), was synthesized through "thiol-ene" click chemistry between the TAT-G-NLS-G-C multifunctional peptide sequence and inorganic octa-diallyl POSS. Cationic PP1 was mixed with the pZNF580 plasmid to obtain stable binary gene complexes (BCPs) with membrane penetrating and nucleus targeting functions. In order to improve BCPs' biocompatibility, cellular uptake, and endosome escape, they were further modified using an anionic polymer of PLL-g-CAGW21%-g-Acon (n = 47%, 57% and 64%) having an EC targeting ligand (CAGW peptide) and a charge reversal moiety (cis-aconitic amide) through electrostatic absorption to obtain ternary gene complexes (TCPs). By adjusting the weight ratio of PP1/pZNF580 plasmid/PLL-g-CAGW21%-g-Acon to 5/1/1.25, TCPs-1 with n = 47%, TCPs-2 with n = 57% and TCPs-3 with n = 64% exhibited a neutral zeta potential and suitable particle size; thus they were used for further biological evaluation. Compared with BCPs (5/1 weight ratio of PP1/pZNF580 plasmid), TCPs exhibited high hemocompatibility and cytocompatibility; more interestingly, they also showed significantly enhanced gene delivery efficiency. The TCP groups achieved perfect transfection effects in the proliferation and migration of human umbilical vein endothelial cells (HUVECs), and especially high neovascularization in vitro and in vivo. Our results demonstrated that the high graft ratio of cis-aconitic amide provided benefits of high biocompatibility and gene delivery efficiency, and the TCPs-3 group showed the optimized transfection efficiency among the three groups. Importantly, HUVECs transfected with TCPs-3 exhibited an outstanding ability to enhance angiogenesis in vivo. In brief, this multifunctional ternary gene system with the EC targeting ligand and membrane penetrating, charge reversal and nucleus targeting functions is a promising platform for the transfection of HUVECs, and may be useful for the treatment of cardiovascular diseases in clinical applications.


Assuntos
Portadores de Fármacos/química , Neovascularização Fisiológica/genética , Peptídeos/química , Transfecção , Amidas/química , Movimento Celular/genética , Proliferação de Células/genética , Células Endoteliais da Veia Umbilical Humana/citologia , Humanos , Concentração de Íons de Hidrogênio , Compostos de Organotecnécio/química , Propriedades de Superfície
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