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1.
Clin Res Hepatol Gastroenterol ; 48(5): 102332, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38574887

RESUMO

BACKGROUND & OBJECTIVES: Sarcopenia is a morbi-mortality risk factor in digestive surgery, though its impact after major hepatectomy (MH) remains unknown. This prospective pilot study investigated whether volume and function of a regenerating liver is influenced by body composition. METHODS: From 2011 to 2016, 125 consecutive patients had computed tomography and 99mTc-labelled-mebrofenin SPECT-scintigraphy before and after MH at day 7 and 1 month for measurements of liver volumes and functions. L3 vertebra muscle mass identified sarcopenia. Primary endpoint was the impact of sarcopenia on regeneration capacities (i.e. volume/function changes and post-hepatectomy liver failure (PHLF) rate). Secondary endpoint was 3-month morbi-mortality. RESULTS: Sarcopenic patients (SP; N = 69) were significantly older than non-sarcopenic (NSP), with lower BMI and more malignancies, but with comparable liver function/volume at baseline. Postoperatively, SP showed higher rates of ISGLS_PHLF (24.6 % vs 10.9 %; p = 0.05) but with comparable rates of severe morbidity (23.2 % vs 16.4 %; p = 0.35), overall (8.7 % vs 3.6 %; p = 0.3) and PHLF-related mortality (8,7 % vs 1.8 %; p = 0.075). After matching on the extent of resection or using propensity score, regeneration and PHLF rates were similar. CONCLUSION: This prospective study using first sequential SPECT-scintigraphy showed that sarcopenia by itself does not affect liver regeneration capacities and short-term postoperative course after MH.


Assuntos
Compostos de Anilina , Glicina , Hepatectomia , Regeneração Hepática , Sarcopenia , Tomografia Computadorizada de Emissão de Fóton Único , Tomografia Computadorizada por Raios X , Humanos , Sarcopenia/diagnóstico por imagem , Sarcopenia/etiologia , Sarcopenia/complicações , Estudos Prospectivos , Masculino , Feminino , Regeneração Hepática/fisiologia , Idoso , Pessoa de Meia-Idade , Projetos Piloto , Tamanho do Órgão , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/diagnóstico por imagem , Compostos Radiofarmacêuticos , Compostos de Organotecnécio , Iminoácidos , Falência Hepática/diagnóstico por imagem , Falência Hepática/etiologia , Falência Hepática/cirurgia
2.
Bioorg Med Chem Lett ; 106: 129773, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38677561

RESUMO

Hypoxia is a common phenomenon in solid tumors, and its presence inhibits the efficacy of tumor chemotherapy and radiotherapy. Accurate measurement of hypoxia before tumor treatment is essential. Three propylene amine oxime (PnAO) derivatives with different substituents attached to 2-nitroimidazole were synthesized in the work, they are 3,3,9,9-tetramethyl-1,11-bis(4-bromo-2-nitro-1H-imidazol-1-yl)-4,8-diazaundecane-2,10-dione dioxime (Br2P2), 3,3,9,9-tetramethyl-1,11-bis(4-methyl-2-nitro-1H-imidazol-1-yl)-4,8-diazaundecane-2,10-dione dioxime (Me2P2) and 3,3,9,9-tetramethyl-1,11-bis(4,5-dimethyl-2-nitro-1H-imidazol-1-yl)-4,8-diazaundecane-2,10-dione dioxime (2Me2P2). The three compounds were radiolabeled with 99mTc to give three complexes([99mTc]Tc-Br2P2, [99mTc]Tc-Me2P2 and [99mTc]Tc-2Me2P2) with good in vitro stability. [99mTc]Tc-Me2P2 with a more suitable reduction potential had the highest hypoxic cellular uptake, compared with [99mTc]Tc-2P2 that have been previously reported, [99mTc]Tc-Br2P2 and [99mTc]Tc-2Me2P2. Biodistribution results in S180 tumor-bearing mice demonstrated that [99mTc]Tc-Me2P2 had the highest tumor-to-muscle (T/M) ratio (12.37 ± 1.16) at 2 h in the four complexes. Autoradiography and immunohistochemical staining results revealed that [99mTc]Tc-Me2P2 specifically targeted tumor hypoxic regions. The SPECT/CT imaging results showed that [99mTc]Tc-Me2P2 could target the tumor site. [99mTc]Tc-Me2P2 may become a potential hypoxia imaging agent.


Assuntos
Nitroimidazóis , Compostos de Organotecnécio , Oximas , Hipóxia Tumoral , Oximas/química , Oximas/síntese química , Nitroimidazóis/química , Nitroimidazóis/síntese química , Animais , Camundongos , Compostos de Organotecnécio/química , Compostos de Organotecnécio/síntese química , Hipóxia Tumoral/efeitos dos fármacos , Compostos Radiofarmacêuticos/química , Compostos Radiofarmacêuticos/síntese química , Compostos Radiofarmacêuticos/farmacologia , Humanos , Distribuição Tecidual , Estrutura Molecular , Linhagem Celular Tumoral , Relação Estrutura-Atividade
3.
Bioorg Med Chem Lett ; 105: 129730, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38583784

RESUMO

Chlorambucil is an alkylating drug that finds application towards chemotherapy of different types of cancers. In order to explore the possibility of utilization of this drug as an imaging agent for early diagnosis of solid tumors, attempt was made to synthesize a 99mTc complex of chlorambucil and evaluate its potential in tumor bearing small animal model. HYNIC-chlorambucil was synthesized by conjugation of HYNIC with chlorambucil via an ethylenediamine linker. All the intermediates and final product were purified and characterized by standard spectroscopic techniques viz. FT-IR, 1H/13C-NMR as well as by mass spectrometry. HYNIC-chlorambucil conjugate was radiolabeled with [99mTc]Tc and found to be formed with > 95 % radiochemical purity via RP-HPLC studies. The partition coefficient (Log10Po/w) of the synthesized complex was found to be -0.78 ± 0.25 which indicated the moderate hydrophilic nature for the complex. Biological behaviour of [99mTc]Tc-HYNIC-chlorambucil, studied in fibrosarcoma bearing Swiss mice, revealed a tumor uptake of about 4.16 ± 1.52 %IA/g at 30 min post-administration, which declined to 1.91 ± 0.13 % IA/g and 1.42 ± 0.14 %IA/g at 1 h and 2 h post-administration, respectively. A comparison of different [99mTc]Tc-chlorambucil derivatives (reported in the contemporary literature) formulated using different methodologies revealed that tumor uptake and pharmacokinetics exhibited by these agents strongly depend on the lipophilicity/hydrophilicity of such agents, which in turn is dependent on the bifunctional chelators used for formulating the radiolabeled chlorambucils.


Assuntos
Clorambucila , Compostos de Organotecnécio , Animais , Humanos , Camundongos , Antineoplásicos Alquilantes/síntese química , Antineoplásicos Alquilantes/química , Antineoplásicos Alquilantes/farmacologia , Linhagem Celular Tumoral , Clorambucila/química , Clorambucila/síntese química , Clorambucila/farmacologia , Estrutura Molecular , Ácidos Nicotínicos/química , Ácidos Nicotínicos/síntese química , Compostos de Organotecnécio/química , Compostos de Organotecnécio/síntese química , Compostos de Organotecnécio/farmacocinética , Compostos Radiofarmacêuticos/síntese química , Compostos Radiofarmacêuticos/química , Tecnécio/química , Distribuição Tecidual
4.
J Am Heart Assoc ; 13(9): e032577, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38639350

RESUMO

BACKGROUND: The goal was to determine the feasibility of mapping the injured-but-not-infarcted myocardium using 99mTc-duramycin in the postischemic heart, with spatial information for its characterization as a pathophysiologically intermediate tissue, which is neither normal nor infarcted. METHODS AND RESULTS: Coronary occlusion was conducted in Sprague Dawley rats with preconditioning and 30-minute ligation. In vivo single-photon emission computed tomography was acquired after 3 hours (n=6) using 99mTc-duramycin, a phosphatidylethanolamine-specific radiopharmaceutical. The 99mTc-duramycin+ areas were compared with infarct and area-at-risk (n=8). Cardiomyocytes and endothelial cells were isolated for gene expression profiling. Cardiac function was measured with echocardiography (n=6) at 4 weeks. In vivo imaging with 99mTc-duramycin identified the infarct (3.9±2.4% of the left ventricle and an extensive area 23.7±2.2% of the left ventricle) with diffuse signal outside the infarct, which is pathologically between normal and infarcted (apoptosis 1.8±1.6, 8.9±4.2, 13.6±3.8%; VCAM-1 [vascular cell adhesion molecule 1] 3.2±0.8, 9.8±4.1, 15.9±4.2/mm2; tyrosine hydroxylase 14.9±2.8, 8.6±4.4, 5.6±2.2/mm2), with heterogeneous changes including scattered micronecrosis, wavy myofibrils, hydropic change, and glycogen accumulation. The 99mTc-duramycin+ tissue is quantitatively smaller than the area-at-risk (26.7% versus 34.4% of the left ventricle, P=0.008). Compared with infarct, gene expression in the 99mTc-duramycin+-noninfarct tissue indicated a greater prosurvival ratio (BCL2/BAX [B-cell lymphoma 2/BCL2-associated X] 7.8 versus 5.7 [cardiomyocytes], 3.7 versus 3.2 [endothelial]), and an upregulation of ion channels in electrophysiology. There was decreased contractility at 4 weeks (regional fractional shortening -8.6%, P<0.05; circumferential strain -52.9%, P<0.05). CONCLUSIONS: The injured-but-not-infarcted tissue, being an intermediate zone between normal and infarct, is mapped in vivo using phosphatidylethanolamine-based imaging. The intermediate zone contributes significantly to cardiac dysfunction.


Assuntos
Modelos Animais de Doenças , Infarto do Miocárdio , Peptídeos , Compostos Radiofarmacêuticos , Ratos Sprague-Dawley , Tomografia Computadorizada de Emissão de Fóton Único , Animais , Infarto do Miocárdio/patologia , Infarto do Miocárdio/metabolismo , Infarto do Miocárdio/diagnóstico por imagem , Masculino , Miocárdio/patologia , Miocárdio/metabolismo , Miócitos Cardíacos/patologia , Miócitos Cardíacos/metabolismo , Bacteriocinas/metabolismo , Estudos de Viabilidade , Ratos , Perfilação da Expressão Gênica/métodos , Função Ventricular Esquerda , Células Endoteliais/metabolismo , Células Endoteliais/patologia , Compostos de Organotecnécio
5.
J Biol Inorg Chem ; 29(2): 187-199, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38607392

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 , Tomografia Computadorizada de Emissão de Fóton Único , Animais , Peptídeos beta-Amiloides/metabolismo , Camundongos , Tecnécio/química , Distribuição Tecidual , Chalcona/química , Compostos Radiofarmacêuticos/química , Compostos Radiofarmacêuticos/farmacocinética , Compostos Radiofarmacêuticos/síntese química , Compostos de Organotecnécio/química , Compostos de Organotecnécio/farmacocinética , Lesões Encefálicas Traumáticas/diagnóstico por imagem , Lesões Encefálicas Traumáticas/metabolismo , Traumatismos Craniocerebrais/diagnóstico por imagem , Masculino , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo
6.
Clin Nucl Med ; 49(6): e284-e285, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38498732

RESUMO

ABSTRACT: A 67-year-old woman complained of rest and postural tremors in her left upper extremity, associated with bradykinesia and gait disorder since 2 years ago, with no significant response to antiparkinsonism drugs. Dopamine transporter SPECT/CT revealed a remarkable area of 99m Tc-TRODAT-1 uptake in a huge tumoral lesion in the right frontotemporal region, compressing and dislocating the right striatum with evidence of significant midline shift. The patient underwent surgical resection with a diagnosis of meningioma on preoperative MRI and postoperative histology report, experiencing a marked recovery in symptoms after 1 month.


Assuntos
Meningioma , Compostos de Organotecnécio , Transtornos Parkinsonianos , Tomografia Computadorizada com Tomografia Computadorizada de Emissão de Fóton Único , Tropanos , Humanos , Feminino , Idoso , Meningioma/diagnóstico por imagem , Meningioma/complicações , Transtornos Parkinsonianos/diagnóstico por imagem , Neoplasias Meníngeas/diagnóstico por imagem , Neoplasias Meníngeas/complicações , Tomografia Computadorizada de Emissão de Fóton Único
7.
J Labelled Comp Radiopharm ; 67(5): 168-179, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38485465

RESUMO

Breast cancer is the most common diagnosed cancer, and the second cause of cancer death among women, worldwide. HER2 overexpression occurred in approximately 15% to 20% of breast cancers. Invasive biopsy method has been used for detection of HER2 overexpression. HER2-targeted imaging via an appropriate radionuclide is a promising method for sensitive and accurate identification of HER2+ primary and metastatic lesions. 99mTc-anti-HER2 scFv can specifically target malignancies and be used for diagnosis of the cancer type and metastasis as well as treatment of breast cancer. We radiolabeled anti-HER2 scFv that was expressed in Escherichia coli and purified through Ni-NTA resin under native condition with 99mTc-tricarbonyl formed from boranocarbonate. HER2-based ELISA, BCA, TLC, and HPLC were used in this study. In the current study, anti-HER2 scFv was lyophilized before radiolabeling. It was found that freeze-drying did not change the binding activity of anti-HER2 scFv to HER2. Results demonstrated direct anti-HER2 scFv radiolabeling by 99mTc-tricarbonyl to hexahistidine sequence (His-tag) without any changes in biological activity and radiochemical purity of around 98%. Stability analysis revealed that 99mTc-anti-HER2 scFv is stable for at least 24 h in PBS buffer, normal saline, human plasma proteins, and histidine solution.


Assuntos
Marcação por Isótopo , Compostos de Organotecnécio , Receptor ErbB-2 , Anticorpos de Cadeia Única , Receptor ErbB-2/metabolismo , Receptor ErbB-2/imunologia , Humanos , Anticorpos de Cadeia Única/química , Compostos de Organotecnécio/química , Estabilidade de Medicamentos , Tecnécio/química , Compostos Radiofarmacêuticos/química
8.
Jpn J Radiol ; 42(5): 508-518, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38351252

RESUMO

PURPOSE: The aim of this study was to develop a novel approach that enhanced diagnostic accuracy in the diagnosis of mild cognitive impairment (MCI) and early Alzheimer's disease (AD) using cerebral perfusion SPECT by minimizing artifacts caused by cerebral atrophy. MATERIALS AND METHODS: [99mTc]-ECD and SPECT studies were performed on 15 cognitively normal patients, 40 patients with MCI, and 16 patients with AD. SPECT images were compared using SPM. The atrophy correction method was incorporated to reduce artifacts through the MRI masking procedure. Regional Z-score, percent extent, and atrophy correction rate were obtained and compared. The Z-score mapping program was structured as a single package that ran semi-automatically. RESULTS: The method significantly reduced regional Z-score in most regions, leading to improved estimates. The mean atrophy correction rate ranged from 10.4 to 12.0%. In MCI and AD, the convexities of the frontal and parietal lobes and the posterior medial cerebrum were particularly sensitive to cerebral atrophy, and the Z-scores were overestimated, whereas the posterior cingulate cortex and the cerebellum were less sensitive. The diagnostic accuracy for MCI increased from 67 to 69% and for AD from 78 to 82%. CONCLUSION: The proposed approach provided more precise Z-scores with less over- or underestimation, artifacts, and improved diagnostic accuracy, being recommended for clinical studies.


Assuntos
Doença de Alzheimer , Artefatos , Atrofia , Disfunção Cognitiva , Cisteína/análogos & derivados , Compostos de Organotecnécio , Compostos Radiofarmacêuticos , Tomografia Computadorizada de Emissão de Fóton Único , Humanos , Doença de Alzheimer/diagnóstico por imagem , Feminino , Masculino , Idoso , Disfunção Cognitiva/diagnóstico por imagem , Tomografia Computadorizada de Emissão de Fóton Único/métodos , Atrofia/diagnóstico por imagem , Pessoa de Meia-Idade , Circulação Cerebrovascular , Idoso de 80 Anos ou mais , Encéfalo/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Sensibilidade e Especificidade
9.
Mol Pharm ; 21(2): 932-943, 2024 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-38225758

RESUMO

P-glycoprotein (P-gp, encoded in humans by the ABCB1 gene and in rodents by the Abcb1a/b genes) is a membrane transporter that can restrict the intestinal absorption and tissue distribution of many drugs and may also contribute to renal and hepatobiliary drug excretion. The aim of this study was to compare the performance and sensitivity of currently available radiolabeled P-gp substrates for positron emission tomography (PET) with the single-photon emission computed tomography (SPECT) radiotracer [99mTc]Tc-sestamibi for measuring the P-gp function in the kidneys and liver. Wild-type, heterozygous (Abcb1a/b(+/-)), and homozygous (Abcb1a/b(-/-)) Abcb1a/b knockout mice were used as models of different P-gp abundance in excretory organs. Animals underwent either dynamic PET scans after intravenous injection of [11C]N-desmethyl-loperamide, (R)-[11C]verapamil, or [11C]metoclopramide or consecutive static SPECT scans after intravenous injection of [99mTc]Tc-sestamibi. P-gp in the kidneys and liver of the mouse models was analyzed with immunofluorescence labeling and Western blotting. In the kidneys, Abcb1a/b() mice had intermediate P-gp abundance compared with wild-type and Abcb1a/b(-/-) mice. Among the four tested radiotracers, renal clearance of radioactivity (CLurine,kidney) was significantly reduced (-83%) in Abcb1a/b(-/-) mice only for [99mTc]Tc-sestamibi. Biliary clearance of radioactivity (CLbile,liver) was significantly reduced in Abcb1a/b(-/-) mice for [11C]N-desmethyl-loperamide (-47%), [11C]metoclopramide (-25%), and [99mTc]Tc-sestamibi (-79%). However, in Abcb1a/b(+/-) mice, CLbile,liver was significantly reduced (-47%) only for [99mTc]Tc-sestamibi. Among the tested radiotracers, [99mTc]Tc-sestamibi performed best in measuring the P-gp function in the kidneys and liver. Owing to its widespread clinical availability, [99mTc]Tc-sestamibi represents a promising probe substrate to assess systemic P-gp-mediated drug-drug interactions and to measure renal and hepatic P-gp function under different (patho-)physiological conditions.


Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP , Metoclopramida , Humanos , Camundongos , Animais , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/genética , Tomografia Computadorizada por Raios X , Subfamília B de Transportador de Cassetes de Ligação de ATP/genética , Tomografia por Emissão de Pósitrons/métodos , Compostos Radiofarmacêuticos , Fígado/diagnóstico por imagem , Tomografia Computadorizada de Emissão de Fóton Único , Rim/diagnóstico por imagem , Nitrilas , Compostos de Organotecnécio , Camundongos Knockout
10.
Nucl Med Commun ; 45(3): 175-180, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38165160

RESUMO

OBJECTIVES: To determine if three new simplified equations for measurement of free mebrofenin clearance give similar results to the equations defined by Ekman et. al ., and to evaluate the properties of all four methods. Regional mebrofenin clearance has been used to predict future remnant liver function and liver failure after regional liver therapy, such as partial hepatic resection. METHODS: The means, standard deviations, and correlations of the free mebrofenin clearance measured by the Ekman method and the three simplified methods were compared in a consecutive series of 26 studies in 20 patients. The fractional change in the blood and free mebrofenin activities were compared, and integrals of normalized blood and free mebrofenin ("effective times") were compared. RESULTS: The average percent free mebrofenin clearance for the Ekman and the first, second and third simplified methods were 13.62 ± 2.88%/min, 12.98 ± 2.97%/min, 12.52 ± 2.81%/min and 15.03 ± 2.27%/min, respectively. The correlations of the new methods with Ekman were 0.97, 0.93 and 0.93. The fractional changes during the measurement interval for the blood and free mebrofenin activities were 0.381 ± 0.065 and 0.329 ± 0.062, difference 0.052, P < 0.5. The integrals of normalized blood and free mebrofenin activities were 2.566 ± 0.160 min and 2.661 ± 0.158 min, difference of 0.094 min and P < 0.05. CONCLUSIONS: The results of the three new methods were similar to the Ekman method. The first simplified method was identified as the lead method for clinical validation in a larger population.


Assuntos
Glicina , Fígado , Compostos de Organotecnécio , Humanos , Cintilografia , Testes de Função Hepática , Compostos de Anilina , Iminoácidos
11.
Lymphat Res Biol ; 22(2): 124-130, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38265788

RESUMO

Background: Breast cancer-related lymphedema (BCRL) remains a significant postcancer treatment challenge with no definitive cure. Recent supermicrosurgical treatments, such as lymphovenous anastomosis (LVA), have shown promise but lack established objective indicators for outcome evaluation. We investigated the utility of Technetium-99m (Tc-99m) lymphoscintigraphy, an imaging technique providing objective information on lymphatic fluid flow, for assessing LVA surgical outcomes. Methods and Results: A retrospective cohort analysis of patients undergoing LVA for BCRL was conducted. Lymphoscintigraphy images pre- and 1-year postsurgery were compared to determine changes in lymphatic fluid flow of 18 patients based on newly defined parameters "uptake ratio" and "washout rates." Statistically significant reduction in the uptake ratio was observed in the forearm at 30 and 60 minutes postinjection phases. In addition, the forearm showed higher washout rate, indicating an improved lymphatic function in the forearm. Conclusion: Tc-99m lymphoscintigraphy can provide valuable objective data for evaluating LVA surgical outcomes in BCRL patients. However, site-specific differences in outcomes highlight the need for individualized surgical planning. Further large-scale studies are necessary to validate these preliminary findings and develop a standardized approach for LVA assessment.


Assuntos
Linfedema Relacionado a Câncer de Mama , Neoplasias da Mama , Vasos Linfáticos , Linfedema , Compostos de Organotecnécio , Humanos , Feminino , Linfocintigrafia , Estudos Retrospectivos , Ácido Fítico , Anastomose Cirúrgica , Resultado do Tratamento
13.
Drug Dev Res ; 85(1): e22138, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38078492

RESUMO

The continuous pursuit of designing an ideal infection imaging agent is a crucial and ongoing endeavor in the field of biomedical research. Duramycin, an antimicrobial peptide exerts its antimicrobial action on bacteria by specific recognition of phosphatidylethanolamine (PE) moiety present on most bacterial membranes, particularly Escherichia coli (E. coli). E. coli membranes contain more than 60% PE. Therefore, duramycin is an attractive candidate for the formulation of probes for in situ visualization of E. coli driven focal infections. The aim of the present study is to develop 99m Tc labeled duramycin as a single-photon emission computed tomography (SPECT)-based agent to image such infections. Duramycin was successfully conjugated with a bifunctional chelator, hydrazinonicotinamide (HYNIC). PE specificity of HYNIC-duramycin was confirmed by a dye release assay on PE-containing model membranes. Radiolabeling of HYNIC-duramycin with 99m Tc was performed with consistently high radiochemical yield (>90%) and radiochemical purity (>90%). [99m Tc]Tc-HYNIC-duramycin retained its specificity for E. coli, in vitro. SPECT and biodistribution studies showed that the tracer could specifically identify E. coli driven infection at 3 h post injection. While 99m Tc-labeled duramycin is employed for monitoring early response to cancer therapy and cardiotoxicity, the current studies have confirmed, for the first time, the potential of utilizing 99m Tc labeled duramycin as an imaging agent for detecting bacteria. Its application in imaging PE-positive bacteria represents a novel and promising advancement.


Assuntos
Bacteriocinas , Escherichia coli , Compostos de Organotecnécio , Compostos de Organotecnécio/química , Distribuição Tecidual , Peptídeos/química , Peptídeos/metabolismo
14.
Amyloid ; 31(1): 22-31, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37530216

RESUMO

BACKGROUND: The significance of measuring 99mTc-labelled-3,3-diphosphono-1,2-propanodicarboxylic acid (99mTc-DPD) in transthyretin (ATTR) cardiac amyloidosis has not been adequately studied. This single-centre observational study evaluated the correlation between 99mTc-DPD scintigraphy and histological amyloid load in endomyocardial biopsy (EMB). METHODS: Twenty-eight patients with biopsy-proven ATTR amyloidosis and concomitantly available 99mTc-DPD scintigraphy were included. Visual Perugini scoring, and (semi-)quantitative analysis of cardiac 99mTc-DPD uptake by planar whole-body imaging and single photon emission computed tomography (SPECT/CT) using regions of interest (ROI) were performed. From this, heart-to-whole-body ratio (H/WB) and heart-to-contralateral-chest ratio (H/CL) were calculated. The histological amyloid load was quantified using two different staining methods. RESULTS: Increased cardiac tracer uptake was documented in all patients (planar: ROImean 129 ± 37 cps; SPECT/CT: ROImean 369 ± 142 cps). Histological amyloid load (19 ± 13%) significantly correlated with Perugini score (r = 0.69, p < .001) as well as with cardiac 99mTc-DPD uptake (planar: r = 0.64, p < .001; H/WB: r = 0.50, p = .014; SPECT/CT: r = 0.53, p = .008; H/CL: r = 0.43, p = .037) (results are shown for correlations with Congo Red-staining). CONCLUSION: In ATTR, cardiac 99mTc-DPD uptake significantly correlated with histological amyloid load in EMB. Further studies are needed to implement thresholds in cardiac 99mTc-DPD uptake measurements for risk stratification and guidance of therapy.


Assuntos
Neuropatias Amiloides Familiares , Amiloidose , Cardiomiopatias , Humanos , Pré-Albumina , Compostos de Organotecnécio , Tomografia Computadorizada por Raios X , Amiloidose/diagnóstico por imagem , Amiloide , Cintilografia , Proteínas Amiloidogênicas , Neuropatias Amiloides Familiares/diagnóstico por imagem , Cardiomiopatias/diagnóstico por imagem
15.
Amyloid ; 31(1): 42-51, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37599395

RESUMO

Aims: Novel ribonucleic acid interference (RNAi) therapeutics such as patisiran and inotersen have been shown to benefit neurologic disease course and quality of life in patients with hereditary transthyretin amyloidosis (ATTRv). We aimed to determine the impact of RNAi therapeutics on myocardial amyloid load using quantitative single photon emission computed tomography/computed tomography (SPECT/CT) imaging in patients with ATTRv-related cardiomyopathy (ATTRv-CM). We furthermore compared them with wild-type ATTR-CM (ATTRwt-CM) patients treated with tafamidis.Methods and results: ATTRv-CM patients underwent [99mTc]-radiolabeled diphosphono-1,2-propanodicarboxylic acid (99mTc-DPD) scintigraphy and quantitative SPECT/CT imaging before and after 12 months (IQR: 11.0-12.0) of treatment with RNAi therapeutics (patisiran: n = 5, inotersen: n = 4). RNAi treatment significantly reduced quantitative myocardial uptake as measured by standardised uptake value (SUV) retention index (baseline: 5.09 g/mL vs. follow-up: 3.19 g/mL, p = .028) in ATTRv-CM patients without significant improvement in cardiac function. Tafamidis treatment resulted in a significant reduction in SUV retention index (4.96 g/mL vs. 3.27 g/mL, p < .001) in ATTRwt-CM patients (historical control cohort: n = 40) at follow-up [9.0 months (IQR: 7.0-10.0)] without beneficial impact on cardiac function.Conclusions: RNAi therapeutics significantly reduce quantitative myocardial uptake in ATTRv-CM patients, comparable to tafamidis treatment in ATTRwt-CM patients, without impact on cardiac function. Serial 99mTc-DPD SPECT/CT imaging may be a valuable tool to quantify and monitor response to disease-specific therapies in both ATTRv-CM and ATTRwt-CM.


Assuntos
Neuropatias Amiloides Familiares , Cardiomiopatias , Humanos , Qualidade de Vida , Compostos de Organotecnécio , Cardiomiopatias/diagnóstico por imagem , Cardiomiopatias/tratamento farmacológico , Cardiomiopatias/genética , Neuropatias Amiloides Familiares/diagnóstico por imagem , Neuropatias Amiloides Familiares/tratamento farmacológico , Neuropatias Amiloides Familiares/genética , Miocárdio
16.
Clin Nucl Med ; 49(2): e87-e89, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38048519

RESUMO

ABSTRACT: We present 99m Tc-HYNIC-TOC SPECT/CT findings in a case of microcystic serous cystadenoma of the pancreatic head. The pancreatic tumor showed intense 99m Tc-HYNIC-TOC uptake mimicking neuroendocrine tumor on SPECT/CT. This case indicates that microcystic serous cystadenoma should be included in the differential diagnosis of 99m Tc-HYNIC-TOC-avid pancreatic masses.


Assuntos
Cistadenoma Seroso , Tumores Neuroendócrinos , Neoplasias Pancreáticas , Humanos , Tumores Neuroendócrinos/diagnóstico por imagem , Tumores Neuroendócrinos/patologia , Tomografia Computadorizada de Emissão de Fóton Único , Octreotida , Compostos de Organotecnécio , Tomografia Computadorizada com Tomografia Computadorizada de Emissão de Fóton Único , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/patologia
17.
Clin Nucl Med ; 49(2): e65-e67, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38048549

RESUMO

ABSTRACT: [ 99m Tc]Tc-DPD (3,3-diphosphono-1,2-propanodicarboxylic acid) scintigraphy is an essential tool for diagnosing transthyretin amyloid cardiac amyloidosis. An 86-year-old woman suffering from heart failure with preserved ejection fraction underwent [ 99m Tc]Tc-DPD scintigraphy and a SPECT/CT for suspected transthyretin amyloid cardiac amyloidosis. The scan showed intracardiac and liver uptake. As the patient had taken intravenous iron on the morning of the scan, we decided to repeat the scan, but this time, it showed no uptake in the heart or the liver. Accordingly, we concluded the first result was a false positive due to drug interaction.


Assuntos
Amiloidose , Cardiomiopatias , Feminino , Humanos , Idoso de 80 Anos ou mais , Pré-Albumina , Compostos de Organotecnécio , Amiloidose/diagnóstico por imagem , Coração , Cintilografia , Amiloide , Cardiomiopatias/diagnóstico por imagem
18.
Pathol Res Pract ; 253: 154941, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38000200

RESUMO

Pancreatic polypeptide cell hyperplasia (PPY-H) is a multiplication of the neuroendocrine cells producing pancreatic polypeptide (PPY). The development and role of PPY-H and its corresponding clinical and imaging findings still need to be fully elucidated. We present 12 cases of PPY-H accompanying pancreatic neuroendocrine neoplasias (NEN). PPY-H was analyzed with the help of immunohistochemistry and confocal microscopy; preoperative clinical data and imaging studies were evaluated retrospectively. We observed PPY-H emerging from pancreatic ducts, and in some cases, we observed simultaneous NKX6.1 positivity in ducts and PPY-H. Additional clinical-pathological correlations suggests that gastrointestinal symptoms (e.g., epigastric pain and cholestasis) could be more related to PPY-H than to NEN hormonal production. In particular cases, SSTR2 expression was strong in PPY-H and correlated with distinguishable accumulation of activity next to NEN on 99 mTc EDDA/Hynic-TOC SPECT/CT. In another case, 18F-FDG-PET/CT showed increased metabolic activity in the area of PPY-H surrounding NEN. Our data suggest that PPY-H originates in the lining of pancreatic ducts. Confirmation of SSTR2 in PPY-H, using immunohistochemistry, suggests the utility of 99 mTc EDDA/Hynic-TOC or 68Ga-DOTA radiotracers in clinical diagnostics; however, studies with larger cohort are needed.


Assuntos
Ácido Edético/análogos & derivados , Tumores Neuroendócrinos , Medicina Nuclear , Neoplasias Pancreáticas , Humanos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Hiperplasia , Polipeptídeo Pancreático , Estudos Retrospectivos , Compostos de Organotecnécio , Neoplasias Pancreáticas/patologia , Tumores Neuroendócrinos/patologia
19.
Hell J Nucl Med ; 26(3): 210-214, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38085837

RESUMO

Extrastriatal accumulation on technetium-99m-([2-[[2-[[[3-(4-chlorophenyl)-8-methyl-8-azabicyclo[3,2,1]oct-2-yl]methyl](2-mercaptoethyl)amino]ethyl]amino]- ethanethiolato(3-)-N2,N2',S2,S2']oxo-[1R-(exo-exo)])(99mTc)-TRODAT-1 is unexpected during nuclear medicine nigrostriatal pathway examinations on 99mTc-TRODAT-1 brain single photon emission computed tomography (SPECT). An 86-year-old female with a history of right hemiparesis, speech expressive difficulties, unstable gait, and bradykinesia on right side was reported. Technetium-99m -TRODAT-1 dopamine transporter SPECT revealed an incidental extrastriatal accumulation of radiotracer in the left anterior frontal region, accompanied by a photopenic area which resulted in the displacement of the left striatum with decreased dopaminergic neuronal function. The brain magnetic resonance imaging (MRI) revealed an invasive meningioma corresponding to the extrastriatal uptake on SPECT, accompanied by edema and mass effect. The patient received surgery and the histopathological results confirmed the diagnosis of atypical meningioma.This study emphasizes the importance of understanding the underlying causes of extrastriatal uptake from 99mTc-TRODAT-1 brain SPECT, which may indicate an invasive brain tumor.


Assuntos
Neoplasias Meníngeas , Meningioma , Feminino , Humanos , Idoso de 80 Anos ou mais , Tecnécio , Meningioma/diagnóstico por imagem , Proteínas da Membrana Plasmática de Transporte de Dopamina , Tomografia Computadorizada de Emissão de Fóton Único/métodos , Compostos de Organotecnécio , Encéfalo/diagnóstico por imagem , Dopamina , Tropanos , Neoplasias Meníngeas/diagnóstico por imagem
20.
Zh Nevrol Psikhiatr Im S S Korsakova ; 123(12): 109-115, 2023.
Artigo em Russo | MEDLINE | ID: mdl-38147390

RESUMO

OBJECTIVE: To develop indications for surgical treatment for positional disorders of blood flow in the vertebral-basilar territory caused by the damage to the V2-V3 segment of the vertebral artery (VA). MATERIAL AND METHODS: One hundred and fourteen patients with systemic and non-systemic dizziness were studied. To assess the state of the VA, blood circulation of the posterior cranial fossa and the base of the brain, ultrasound duplex scanning of blood vessels, selective angiography, MRI, single photon emission computed tomography (SPECT) of the brain and neuropsychological testing were performed. Patients were divided into three groups according to the severity of clinical manifestations of vertebrobasilar insufficiency (VBI). RESULTS: According to ultrasound data, patients of the third group with severe VBI had signs of extravasal compression in 94.3% of cases. In the same group, there was an increase in the systolic-diastolic (S/D) ratio by more than 2.5-3 times, as well as an increase in the resistive index (RI) by more than 1.75 units and pulsation index (PI) more than 2.2 units in V2-V3 segments of VA. In 42.9% of patients of the third group, zones of a decrease in the accumulation of 99mTc-ECD by more than 20% were found in the occipital region during the De Klein test. A direct correlation was established between the clinical manifestations of VBI and a decrease in perfusion during SPECT by 20% or more with the De Klein test (r=0.7). We developed an algorithm for diagnosing high-grade VBI with subsequent identification of a causal relationship with extravasal component effects on VA in the second segment. Indications for surgical intervention were determined in 33 patients with clinical manifestations of blood flow decompensation in the posterior cranial fossa. CONCLUSION: Decreased blood flow velocity in the vertebral or basilar artery by more than 50% with a decrease in PI, breath holding index <0.7 in the hypercapnic test, and no increase in blood flow velocity in a phototest and, in addition, the >20% defect of 99mTc-ECD accumulation in the posterior parts of the brain during SPECT with a De Klein test are the criteria for decompensation of blood flow in the vertebral-basilar territory, requiring surgical correction.


Assuntos
Artéria Vertebral , Insuficiência Vertebrobasilar , Humanos , Artéria Vertebral/diagnóstico por imagem , Insuficiência Vertebrobasilar/complicações , Insuficiência Vertebrobasilar/diagnóstico por imagem , Compostos de Organotecnécio , Algoritmos
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