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1.
Clin Nucl Med ; 46(1): e34-e35, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33031249

RESUMO

Primary intestinal lymphangiectasia is an unusual cause of protein losing enteropathy due to either congenital malformation or obstruction of lymphatics of intestine. The disease can affect all or only a small part of the small intestine. Peripheral lymphedema may be associated. The diagnosis is based on endoscopic and histopathological findings. A 30-year-old woman presents lower extremity edema with hypoproteinemia, hypoalbuminemia, and hypogammaglobulinemia. Tc-labeled human serum albumin nanocolloid lymphoscintigraphy of the lower extremity demonstrated a dermal backflow in the right extremity consistent with lymphedema and an unusual ileal uptake on SPECT/CT. Diagnosis is confirmed on histopathological evaluation of biopsy of ileum.


Assuntos
Linfangiectasia Intestinal/diagnóstico por imagem , Linfangiectasia Intestinal/patologia , Compostos de Organotecnécio , Albumina Sérica , Tomografia Computadorizada com Tomografia Computadorizada de Emissão de Fóton Único , Adulto , Biópsia , Feminino , Humanos , Linfangiectasia Intestinal/complicações , Sensibilidade e Especificidade
2.
Clin Nucl Med ; 46(1): 71-73, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32956111

RESUMO

Adrenal Castleman disease is very rare. We reported image findings of a right adrenal mass in a 75-year-old man on Tc-HYNIC-TOC scan and FDG PET/CT. There was obviously elevated Tc-HYNIC-TOC activity, but the intensity of FDG activity was remarkable. Pheochromocytoma was initially suspected. However, pathology from resected specimen showed adrenal Castleman disease.


Assuntos
Doenças das Glândulas Suprarrenais/diagnóstico por imagem , Hiperplasia do Linfonodo Gigante/diagnóstico por imagem , Fluordesoxiglucose F18 , Octreotida/análogos & derivados , Compostos de Organotecnécio , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Idoso , Humanos , Masculino
3.
Clin Nucl Med ; 46(1): e8-e10, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33031234

RESUMO

A 68-year-old man with hereditary hypercoagulability was referred to nuclear medicine for elevated aminotransferases after a recent living-donor liver transplant. A hepatic infarction was suspected. A Tc-mebrofenin SPECT/CT was performed and showed decreased radiotracer uptake in a wedge-shaped distribution in the anterior liver suggestive of a hepatic infarction. Subsequently, an enhanced MRI corroborated the diagnosis. Oral anticoagulation therapy was then initiated, and aminotransferases soon normalized.


Assuntos
Infarto Hepático/diagnóstico por imagem , Iminoácidos , Compostos de Organotecnécio , Tomografia Computadorizada com Tomografia Computadorizada de Emissão de Fóton Único , Idoso , Infarto Hepático/tratamento farmacológico , Infarto Hepático/fisiopatologia , Humanos , Transplante de Fígado , Masculino
4.
Br J Radiol ; 93(1115): 20200775, 2020 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-32880475

RESUMO

OBJECTIVES: The isotope bone scan (IBS) is the gold-standard imaging modality for detecting skeletal metastases as part of prostate cancer staging. However, its clinical utility for assessing skeletal metastatic burden is limited due to the need for subjective interpretation. We designed and tested a novel custom software tool, the Metastatic Bone Scan Tool (MetsBST), aimed at improving interpretation of IBSs, and compared its performance with that of an established software programme. METHODS: We used IBS images from 62 patients diagnosed with prostate cancer and suspected bone metastases to design and implement MetsBST in MATLAB by defining thresholds used to identify the texture and size of metastatic bone lesions. The results of MetsBST were compared with those of the commercially available automated Bone Scan Index (aBSI) with regression analysis. RESULTS: There was strong agreement between the MetsBST and aBSI results (R2 = 0.9189). In a subregional analysis, MetsBST quantified the extent of metastatic disease in multiple bone sites in patients receiving multimodality therapy (radium-223 and external beam radiotherapy) to illustrate the differences in bone metastatic response to different treatments. CONCLUSION: The results of MetsBST and the commercial software aBSI were highly consistent. MetsBST introduces novel clinical utility by its ability to differentiate between the responses of different bone metastases to multimodality therapies. ADVANCES IN KNOWLEDGE: MetsBST reduces the variability in assessment of tumour burden caused by subjective interpretation. Therefore, it is a useful aid to physicians reporting nuclear medicine scans, and may improve decision-making in the treatment of metastatic prostate cancer.


Assuntos
Neoplasias Ósseas/diagnóstico por imagem , Neoplasias Ósseas/secundário , Osso e Ossos/diagnóstico por imagem , Neoplasias da Próstata/patologia , Design de Software , Idoso , Idoso de 80 Anos ou mais , Neoplasias Ósseas/patologia , Neoplasias Ósseas/radioterapia , Ácido Etidrônico , Humanos , Masculino , Pessoa de Meia-Idade , Compostos de Organotecnécio , Neoplasias de Próstata Resistentes à Castração/patologia , Compostos Radiofarmacêuticos , Análise de Regressão , Carga Tumoral , Bexiga Urinária/diagnóstico por imagem
5.
Clin Nucl Med ; 45(9): e411-e412, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32657868

RESUMO

This is a case of a 63-year-old man who presented with acute melena and low hemoglobin. Upper and lower gastrointestinal evaluations failed to localize the bleeding focus. Tc-RBC planar scintigraphy identified 2 sites of suspected bleeding in the lower abdomen area. Subsequent SPECT/CT was performed and identified the precise main focus of active bleeding, the second and third parts of the duodenum, and also described the blood accumulation in the jejunum. Esophagogastroduodenoscopy was immediately performed, and results confirmed spurting blood from the small vessel with multiple ulcers in the second part of the duodenum.


Assuntos
Duodeno/diagnóstico por imagem , Eritrócitos/metabolismo , Melena/diagnóstico por imagem , Compostos de Organotecnécio/metabolismo , Tomografia Computadorizada com Tomografia Computadorizada de Emissão de Fóton Único , Endoscopia do Sistema Digestório , Humanos , Masculino , Pessoa de Meia-Idade
6.
Clin Nucl Med ; 45(8): e349-e357, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32558706

RESUMO

OBJECTIVE: This study aims to investigate the value of Tc-MIP-1404 SPECT/CT for assessment of whole-body tumor burden and treatment response in patients with biochemical recurrence of prostate cancer who undergo androgen deprivation therapy (ADT) or external beam radiation therapy (EBRT). METHODS: A total of 125 patients with biochemical recurrence of prostate cancer underwent Tc-MIP-1404 SPECT/CT. All 364 prostate-specific membrane antigen (PSMA)-positive lesions in the field of view were assessed quantitatively to calculate PSMA-derived metabolic tumor parameters, including whole-body PSMA tumor volume and whole-body total lesion PSMA. These metrics were correlated with serum prostate-specific antigen (PSA) levels and Gleason scores. In a subset of 50 patients who underwent Tc-MIP-1404 SPECT/CT before the initiation of ADT or EBRT, TL-PSMA and SUVmax were compared with radiographic response assessment by CT based on RECIST 1.1 and to biochemical response (BR) determined by changes in serum PSA levels. RESULTS: Serum PSA levels correlated with SUVmax, whole-body PSMA tumor volume, and whole-body total lesion PSMA in patients with 1 and in those with more than 1 PSMA-positive lesion (P < 0.05). The correlations were significant for both well-differentiated (Gleason score ≤7) and poorly differentiated tumors (Gleason score ≥8) (P < 0.05). The agreement between TL-PSMA derived from SPECT and BR in patients who underwent Tc-MIP-1404 SPECT/CT before and after initiation of ADT was 80% (95% confidence interval [CI], 0.43-0.91; Cohen κ = 0.68; P < 0.05); in these patients, the agreement between TL-PSMA and CT was 60% (95% CI, 0.20-0.72; Cohen κ = 0.46; P < 0.05) and the agreement between BR and CT was 52% (0.07-0.61; Cohen κ = 0.34; P < 0.05). Comparable results were found for patients who underwent SPECT/CT before and after initiation of EBRT, with the strongest agreement between TL-PSMA and BR (80%; 95% CI, 0.38-0.93; Cohen κ = 0.66; P < 0.05) compared with the agreement between TL-PSMA and CT (60%; 95% CI, 0.13-0.69; Cohen κ = 0.69; P < 0.05) and between BR and CT (48%; 95% CI, 0-0.54; Cohen κ = 0.26; P = 0.11). Discordant findings between SPECT and CT were most likely due to limitations in the assessment of small lymph node metastases and bone involvement, which were detectable on SPECT but not on CT. CONCLUSIONS: The results of our study show that Tc-MIP-1404 SPECT/CT is a promising method for the evaluation of treatment response in patients with biochemical recurrence of prostate cancer who undergo either ADT or EBRT. TL-PSMA for assessment of treatment response has the strongest correlation with serum PSA levels, superior to SUVmax-based evaluation and response assessment based on CT data and RECIST 1.1.


Assuntos
Compostos de Organotecnécio , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/terapia , Tomografia Computadorizada com Tomografia Computadorizada de Emissão de Fóton Único , Carga Tumoral , Idoso , Antagonistas de Androgênios/uso terapêutico , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Recidiva , Resultado do Tratamento
7.
Clin Nucl Med ; 45(10): e445-e446, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32332305

RESUMO

We describe the extrastriatal accumulation of dopamine transporter imaging agent Tc-TRODAT in the peri-infarct area in a 75-year-old man referred for dopamine transporter SPECT imaging with a suspicion of idiopathic Parkinson disease.


Assuntos
Infarto/metabolismo , Compostos de Organotecnécio/metabolismo , Tropanos/metabolismo , Idoso , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Proteínas da Membrana Plasmática de Transporte de Dopamina/metabolismo , Humanos , Infarto/complicações , Infarto/diagnóstico por imagem , Masculino , Doença de Parkinson/complicações , Tomografia Computadorizada de Emissão de Fóton Único
9.
Dalton Trans ; 49(14): 4559-4569, 2020 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-32202264

RESUMO

Two tridentate ligand systems bearing N-heterocyclic carbene (NHC), amine and carboxylate donor groups coupled to benzothiazole- or stilbene-based amyloid binding moieties were synthesised. Reaction of the imidazolium salt containing pro-ligands with Re(CO)5Cl yielded the corresponding rhenium metal complexes which were characterised by NMR, and X-ray crystallography. These ligands are of interest for the potential preparation of technetium-99m imaging agents for Alzheimer's disease and the capacity of these rhenium complexes bind to amyloid fibrils composed of amyloid-ß peptide and amyloid plaques in human frontal cortex brain tissue was evaluated using fluorescence microscopy. These studies show that the complexes bound efficiently to amyloid-ß fibrils and some evidence of binding to amyloid-ß plaques.


Assuntos
Doença de Alzheimer/diagnóstico por imagem , Peptídeos beta-Amiloides/química , Complexos de Coordenação/química , Compostos de Organotecnécio/química , Aminas/química , Benzotiazóis/química , Sítios de Ligação , Ácidos Carboxílicos/química , Complexos de Coordenação/síntese química , Humanos , Ligantes , Estrutura Molecular , Compostos de Organotecnécio/síntese química , Córtex Pré-Frontal/patologia , Rênio/química , Estilbenos/química
10.
Mayo Clin Proc ; 95(3): 449-458, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32138878

RESUMO

OBJECTIVE: To determine if heparin labeled with 99mTechnetium (99mTc) could be an imaging probe to detect eosinophil-related inflammation in eosinophilic esophagitis and to determine the biodistribution and radiation dosimetry of 99mTc-heparin oral administration using image-based dosimetry models with esophageal modeling. METHODS: Freshly prepared 99mTc-heparin was administered orally to 5 research subjects. Radioactivity was measured by whole-body scintigraphy and single-photon emission computed tomography during the 24 hours postadministration. Following imaging, endoscopic examination was performed. The biodistribution of esophageal radioactivity was compared with endoscopic findings, eosinophil counts in biopsy tissues, and immunostaining for eosinophil granule major basic protein-1 (eMBP1). These studies were conducted from July 1, 2013, until April 22, 2017. RESULTS: Oral administration of 99mTc-heparin was well tolerated in all 5 subjects. The entire esophagus could be visualized dynamically during oral administration. Bound esophageal radioactivity marked areas of inflammation as judged by endoscopy scores, by eosinophils per high power field and by localization of eMBP1 using immunostaining. Ninety percent of the radioactivity did not bind to the esophagus and passed through the gastrointestinal tract. CONCLUSION: The biodistribution of ingested 99mTc-heparin is almost exclusively localized to the gastrointestinal tract. Radiation exposure was highest in the lower gastrointestinal tract and was comparable with other orally administered diagnostic radiopharmaceuticals. The use of swallowed 99mTc-heparin may aid in assessing eosinophil-related inflammation in the esophagus.


Assuntos
Esofagite Eosinofílica/diagnóstico por imagem , Heparina/administração & dosagem , Compostos de Organotecnécio/administração & dosagem , Compostos Radiofarmacêuticos/administração & dosagem , Tomografia Computadorizada de Emissão de Fóton Único , Administração Oral , Adulto , Esofagoscopia , Humanos , Masculino , Pessoa de Meia-Idade , Distribuição Tecidual , Imagem Corporal Total
11.
J Surg Res ; 251: 239-247, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32172010

RESUMO

BACKGROUND: Our previous studies showed that neutrophil infiltration and activation plays an important role in the pathogenesis of abdominal aortic aneurysms (AAA). However, there is a lack of noninvasive, inflammatory cell-specific molecular imaging methods to provide early diagnosis of AAA formation. Formyl peptide receptor 1 (FPR1) is rapidly upregulated on neutrophils during inflammation. Therefore, it is hypothesized that the use of cinnamoyl-F-(D)L-F-(D)L-F-K (cFLFLF), a PEGylated peptide ligand that binds FPR1 on activated neutrophils, would permit accurate and noninvasive diagnosis of AAA via single-photon emission computed tomography (SPECT) imaging. MATERIALS AND METHODS: Male C57BL/6 (wild-type) mice were treated with topical elastase (0.4 U/mL type 1 porcine pancreatic elastase) or heat-inactivated elastase (control), and aortic diameter was measured by video micrometry. Comparative histology was performed on Day 14 to assess neutrophil infiltration in aortic tissue. We performed near-infrared fluorescence imaging using c-FLFLF-Cy7 probe on Days 7 and 14 postelastase treatment and measured fluorescence intensity ex vivo in excised aortic tissue. A separate group of animals were injected with 99mTc-c-FLFLF 2 h before SPECT imaging on Day 14 using a SPECT/computed tomography/positron emission tomography trimodal scanner. Coexpression of neutrophils with c-FLFLF was also performed on aortic tissue by immunostaining on Day 14. RESULTS: Aortic diameter was significantly increased in the elastase group compared with controls on Days 7 and 14. Simultaneously, a marked increase in neutrophil infiltration and elastin degradation as well as decrease in smooth muscle integrity were observed in aortic tissue after elastase treatment compared with controls. Moreover, a significant increase in fluorescence intensity of c-FLFLF-Cy7 imaging probe was also observed in elastase-treated mice on Day 7 (approximately twofold increase) and Day 14 (approximately 2.5-fold increase) compared with respective controls. SPECT imaging demonstrated a multifold increase in signal intensity for 99mTc-cFLFLF radiolabel probe in mice with AAA compared with controls on Day 14. Immunostaining of aortic tissue with c-FLFLF-Cy5 demonstrated a marked increase in coexpression with neutrophils in AAA compared with controls. CONCLUSIONS: cFLFLF, a novel FPR1 ligand, enables quantifiable, noninvasive diagnosis and progression of AAAs. Clinical application of this inflammatory, cell-specific molecular probe using SPECT imaging may permit early diagnosis of AAA formation, enabling targeted therapeutic interventions and preventing impending aortic rupture.


Assuntos
Aneurisma Aórtico/diagnóstico por imagem , Infiltração de Neutrófilos , Receptores de Formil Peptídeo/metabolismo , Tecnécio/metabolismo , Tomografia Computadorizada de Emissão de Fóton Único , Animais , Ligantes , Masculino , Camundongos Endogâmicos C57BL , Imagem Óptica , Compostos de Organotecnécio , Receptores de Formil Peptídeo/agonistas , Tecnécio/química
12.
Int J Gynecol Cancer ; 30(3): 325-331, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32029429

RESUMO

OBJECTIVE: To evaluate the relationship between pelvic/para-aortic sentinel lymph node status and two different injection sites of 99m-technetium (99mTc)-labeled phytate in patients with endometrial cancer. METHODS: This was a randomized controlled trial involving 81 patients with endometrial cancer. In the cervical group (n=40), injections of 99mTc were performed at the 3 and 9 o'clock positions of the uterine cervix. In the endometrial group (n=41), 99mTc was injected into the fundal endometrium using a transcervical catheter. Sentinel lymph nodes were detected through pre-operative lymphoscintigraphy and intra-operatively using a handheld gamma probe. All patients underwent complete pelvic and para-aortic lymphadenectomy procedures. Pathologic ultra-staging was performed with immunostaining for cytokeratin in sentinel lymph nodes after routine hematoxylin and eosin histological examinations. The primary endpoint was the estimation of detection rates, sensitivity, false-negative rates, negative predictive value, and analysis of the distribution of pelvic and para-aortic sentinel lymph nodes. RESULTS: The rate of detection of at least one sentinel lymph node, sensitivity, and the negative predictive value was 80%, 66.6%, 96.6% for the cervical group and 85%, 66.6%, 96.9% for the endometrial group, respectively. False-negative sentinel lymph nodes were detected in one patient from each group . There was no significant difference between the groups in terms of total sentinel lymph node count, sentinel pelvic lymph node count, and pelvic bilaterality, but the para-aortic sentinel lymph node count was significantly higher in the endometrial group (p<0.001). Ultra-staging examination of the pelvic sentinel lymph nodes revealed isolated tumor cells in one patient from each group. CONCLUSION: Transcervical endometrial tracer injection in endometrial cancer revealed similar pelvic but significantly higher para-aortic sentinel lymph node detection.


Assuntos
Neoplasias do Endométrio/diagnóstico por imagem , Compostos de Organotecnécio/administração & dosagem , Ácido Fítico/administração & dosagem , Compostos Radiofarmacêuticos/administração & dosagem , Biópsia de Linfonodo Sentinela/métodos , Linfonodo Sentinela/diagnóstico por imagem , Idoso , Aorta , Neoplasias do Endométrio/patologia , Neoplasias do Endométrio/cirurgia , Feminino , Humanos , Linfonodos/diagnóstico por imagem , Linfonodos/patologia , Linfonodos/cirurgia , Linfocintigrafia/métodos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Pelve , Estudos Prospectivos , Linfonodo Sentinela/patologia , Linfonodo Sentinela/cirurgia
13.
Circ Cardiovasc Imaging ; 13(2): e009769, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-32069116

RESUMO

BACKGROUND: Measurement of myocardial blood flow (MBF) with single photon emission computed tomography (SPECT) is feasible using cardiac cameras with solid-state detectors. SPECT MBF has been shown to be accurate when compared with positron emission tomography MBF measured in the same patients. However, the value of a test result applied to an individual patient depends strongly on the precision or repeatability of the test. The purpose of our study is to measure the precision of SPECT MBF measurements using 99mTc-tetrofosmin and a solid-state cardiac camera. METHODS: SPECT MBF was measured in 30 patients and repeated at a mean interval of 18 days. MBF was evaluated from images with and without attenuation correction based on a separately acquired CT scan. The dynamic images were processed independently by 2 operators using in-house kinetic analysis software that applied a 1-tissue-compartment model. The K1 rate constant was converted to MBF using previously determined extraction fraction corrections. Correction for patient body motion was applied manually. RESULTS: The average coefficient of variation (COV) in the differences between the 2 MBF measurements was between 28% and 31%. The interobserver COV was between 11% and 15%. Myocardial flow reserve is the ratio of MBF measured at stress and rest, and the COV is correspondingly higher. The COV for the difference in repeated myocardial flow reserve was 33% to 38%, whereas the interobserver COV was 13% to 22%. CONCLUSIONS: The COV for the difference in SPECT MBF measurements obtained on separate days is 28% to 31%. The corresponding COV for myocardial flow reserve is 33% to 38%.


Assuntos
Doença da Artéria Coronariana/diagnóstico , Circulação Coronária/fisiologia , Vasos Coronários/diagnóstico por imagem , Compostos Organofosforados/farmacologia , Compostos de Organotecnécio/farmacologia , Fluxo Sanguíneo Regional/fisiologia , Tomografia Computadorizada de Emissão de Fóton Único/métodos , Idoso , Doença da Artéria Coronariana/fisiopatologia , Vasos Coronários/fisiopatologia , Feminino , Humanos , Masculino , Valor Preditivo dos Testes , Curva ROC , Compostos Radiofarmacêuticos/farmacologia
14.
Appl Radiat Isot ; 158: 109047, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31989931

RESUMO

The specific uptake of 99mTc radiolabeled Staphylococcus aureus aptamers in the infectious foci was evaluated by scintigraphic imaging of infection-bearing mice. The radiotracer uptake was inhibited by non-radiolabeled aptamers in a competition assay. In addition, when a different number of bacterial cells was used to infect mice an increase in the target/non-target ratios of images correlated with the increase of CFU per gram of tissue was verified. These results confirmed that 99mTc-aptamers were specific to bacterial focus and the level of uptake was dependent on the number of bacterial cells.


Assuntos
Aptâmeros de Nucleotídeos/farmacocinética , Compostos de Organotecnécio/farmacocinética , Infecções Estafilocócicas/diagnóstico por imagem , Staphylococcus aureus/metabolismo , Animais , Contagem de Colônia Microbiana , Eletroforese em Gel de Ágar , Estudos de Avaliação como Assunto , Camundongos , Cintilografia , Infecções Estafilocócicas/metabolismo , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus/isolamento & purificação
15.
Molecules ; 25(2)2020 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-31936303

RESUMO

The diaminedithiol (N2S2) tetradentate ligand constitutes a useful chelating molecule for preparing 99mTc-labeled compounds of high in vivo stability in high radiochemical yields. However, since the thiol groups in the N2S2 ligand are easy to be oxidized to disulfide bonds, they need to be protected with an appropriate protecting group, which hinders the broad applications of the N2S2 ligand for radiopharmaceuticals. In this study, a Zn chelate of N2S2 was evaluated as a precursor for purification-free 99mTc-labeled N2S2 under the mild and simple procedure. Zn-N2S2 was prepared by reacting Zn acetate with N2S2, and the Zn-N2S2 remained stable under aerobic conditions at room temperature. 99mTc-N2S2 was obtained over 90% radiochemical yields at room temperature by a one-pot reaction, consisting of Zn-N2S2 (10-5 M), 99mTcO4-, ethylenediaminetetraacetic acid (EDTA), and a reducing agent (Sn2+) at pH = 5.5 to 7.5. 99mTc-N2S2 was also obtained over 90% radiochemical yields when the reaction was conducted in the presence of an equimolar amount of IgG antibody. These findings indicate the Zn complex of N2S2 ligand constitutes a stable and useful precursor to prepare 99mTc-labeled N2S2 compounds in high yields under the mild and simple procedure.


Assuntos
Compostos de Organotecnécio/química , Compostos de Sulfidrila/química , Zinco/química , Cromatografia Líquida de Alta Pressão , Cromatografia de Fase Reversa , Ligantes , Compostos de Organotecnécio/síntese química , Compostos de Sulfidrila/síntese química
16.
Eur J Med Chem ; 188: 112032, 2020 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-31926467

RESUMO

Overexpression and amplification of cyclin-dependent kinase 4/6 (CDK4/6) occur in many cancers and may be the cause of resistance to CDK4/6 inhibitors in preclinical models. However, there are few investigations on the assessment of CDK4/6 expression in tumors or other tissues. Palbociclib, which was approved in 2015 to treat ER+/HER2-breast cancer in combination with letrozole, is a selective CDK4/6 inhibitor. In this study, an intermediate (compound 3), which could be hydrolyzed into the ligand (compound L) consisting of palbociclib as the bioactive molecule and 6-hydrazino nicotinamide (HYNIC) as the bifunctional chelator, was synthesized. Compound L was radiolabeled with 99mTc using tricine/TPPTS or tricine/TPPMS as co-ligands. 99mTc-tricine-TPPTS-L and 99mTc-tricine-TPPMS-L were prepared with high radiochemical purity without postlabeling purification. They had great in vitro stability. Both radiotracers were hydrophilic, but 99mTc-tricine-TPPTS-L had a lower log P value. In vitro cell uptake studies in MCF-7 cells showed that cellular uptake was blocked by preincubation with palbociclib, suggesting a CDK4/6-mediated uptake mechanism. Biodistribution in mice bearing MCF-7 tumors showed that 99mTc-tricine-TPPTS-L had higher tumor uptake than 99mTc-tricine-TPPMS-L, while they had comparable tumor-to-muscle and tumor-to-blood ratios. Radioactivity accumulation in tumors was obvious in micro-SPECT/CT images with 99mTc-tricine-TPPTS-L. When mice were preinjected with palbociclib, tumor uptake of 99mTc-tricine-TPPTS-L significantly decreased and the tumor accumulation was clearly lost, confirming CDK4/6 specificity. All results in this work indicated that 99mTc-tricine-TPPTS-L is a promising tumor imaging agent that targets CDK4/6.


Assuntos
Neoplasias da Mama/diagnóstico por imagem , Hidrazinas/química , Niacinamida/análogos & derivados , Compostos de Organotecnécio/química , Piperazinas/química , Piridinas/química , Compostos Radiofarmacêuticos/química , Neoplasias da Mama/metabolismo , Quinase 4 Dependente de Ciclina/antagonistas & inibidores , Quinase 4 Dependente de Ciclina/metabolismo , Quinase 6 Dependente de Ciclina/antagonistas & inibidores , Quinase 6 Dependente de Ciclina/metabolismo , Relação Dose-Resposta a Droga , Humanos , Hidrazinas/farmacologia , Células MCF-7 , Estrutura Molecular , Niacinamida/química , Niacinamida/farmacologia , Compostos de Organotecnécio/síntese química , Compostos de Organotecnécio/farmacologia , Piperazinas/farmacologia , Piridinas/farmacologia , Compostos Radiofarmacêuticos/síntese química , Compostos Radiofarmacêuticos/farmacologia , Relação Estrutura-Atividade , Distribuição Tecidual
17.
Inorg Chem ; 59(4): 2367-2378, 2020 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-31984731

RESUMO

Reaction of [ReOCl3(PPh3)2] or [ReO2I(PPh3)2] with 2,2'-diphenylglycine (dpgH2) in refluxing ethanol afforded the air-stable complex [ReO(dpgH)(dpg)(PPh3)] (1). Treatment of [ReO(OEt)I2(PPh3)2] with 1,2,3-triaza-7-phosphaadamantane (PTA) afforded the complex [ReO(OEt)I2(PTA)2] (2). Reaction of [ReOI2(PTA)3] with dpgH2 led to the isolation of the complex [Re(NCPh2)I2(PTA)3]·0.5EtOH (3·0.5EtOH). A similar reaction but using [ReOX2(PTA)3] (X = Cl, Br) resulted in the analogous halide complexes [Re(NCPh2)Cl2(PTA)3]·2EtOH (4·2EtOH) and [Re(NCPh2)(PTA)3Br2]·1.6EtOH (5·1.6EtOH). Using benzilic acid (2,2'-diphenylglycolic acid, benzH) with 2 afforded the complex [ReO(benz)2(PTA)][PTAH]·EtOH (6·EtOH). The potential for the formation of complexes using radioisotopes with relatively short half-lives suitable for nuclear medicine applications by developing conditions for [Re(NCPh2)(dpg)I(PTA)3] (7)[ReO4]- in a 4 h time scale was investigated. A procedure for the technetium analog of complex [Re(NCPh2)I2(PTA)3] (3) from 99mTc[TcO4]- was then investigated. The molecular structures of 1-7 are reported; complexes 3-7 have been studied using in vitro cell assays (HeLa, HCT116, HT-29, and HEK 293) and were found to have IC50 values in the range of 29-1858 µM.


Assuntos
Complexos de Coordenação/química , Complexos de Coordenação/toxicidade , Linhagem Celular Tumoral , Complexos de Coordenação/síntese química , Células HEK293 , Humanos , Estrutura Molecular , Compostos de Organotecnécio/síntese química , Compostos de Organotecnécio/química , Fosfinas/síntese química , Fosfinas/química , Fosfinas/toxicidade , Rênio/química , Solubilidade , Água/química
18.
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
19.
Clin Nucl Med ; 45(3): e148-e150, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31977466

RESUMO

We present the case of a 69-year-old man with history of prostate carcinoma treated with prostatectomy and subsequently with external beam radiotherapy and hormone therapy because of biochemical recurrences. More than 10 years after the diagnosis, follow-up Tc-HDP bone scans and SPECT/CT images demonstrated an incidental diagnosis of osteoblastic pleural plaques that quickly evolve to mesothelioma. PET/CT achieved the definitive diagnosis by guiding the biopsy to the highest and most accessible focus of glucidic hypermetabolism. Our case report raises the association between prostate cancer patients treated with external beam radiotherapy and the development of pleural mesothelioma despite having no history of exposure to asbestos.


Assuntos
Neoplasias Pulmonares/diagnóstico por imagem , Mesotelioma/diagnóstico por imagem , Neoplasias Pleurais/diagnóstico por imagem , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Neoplasias da Próstata/complicações , Tomografia Computadorizada com Tomografia Computadorizada de Emissão de Fóton Único , Idoso , Difosfonatos , Fluordesoxiglucose F18 , Humanos , Neoplasias Pulmonares/complicações , Masculino , Mesotelioma/complicações , Compostos de Organotecnécio , Neoplasias Pleurais/complicações , Neoplasias da Próstata/sangue , Compostos Radiofarmacêuticos
20.
Clin Nucl Med ; 45(3): 250-251, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31977492

RESUMO

We report of a 71-year-old woman with a 2-cm somatostatin receptor-positive intrapancreatic lesion almost misdiagnosed as neuroendocrine neoplasm. By additional red blood cell scintigraphy with heat-damaged erythrocytes, the lesion was identified as an intrapancreatic accessory spleen, and unnecessary operation (which was already planned) could be avoided. This case report reminds colleagues to consider accessory spleen as differential diagnosis for somatostatin receptor-positive lesions even when located inside the pancreas. In doubtful cases, a scintigraphy with heat-damaged erythrocytes is a very useful and complementary imaging method and should be performed before any planning of surgery.


Assuntos
Tumores Neuroendócrinos/diagnóstico por imagem , Neoplasias Pancreáticas/diagnóstico por imagem , Tomografia Computadorizada com Tomografia Computadorizada de Emissão de Fóton Único , Esplenopatias/diagnóstico por imagem , Idoso , Diagnóstico Diferencial , Feminino , Humanos , Octreotida/análogos & derivados , Compostos de Organotecnécio , Compostos Radiofarmacêuticos
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