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1.
Radiol Clin North Am ; 58(6): 1135-1146, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33040853

RESUMO

This article is a summary of the most up-to-date applications of radiopharmaceuticals to the diagnosis and therapy of benign and malignant diseases involving endocrine or neuroendocrine organs of the head and neck, focusing on radiotracers approved by the US Food and Drug Administration, such as I-123- and I-131-sodium iodide, F-18-fluorodeoxyglucose, Tc99m-sestamibi, as well as the more recently approved tracers Ga-68 DOTATATE and Lu-177 DOTATATE.


Assuntos
Neoplasias de Cabeça e Pescoço/diagnóstico por imagem , Imagem Molecular/métodos , Tumores Neuroendócrinos/diagnóstico por imagem , Tomografia por Emissão de Pósitrons/métodos , Compostos Radiofarmacêuticos/farmacologia , Feminino , Neoplasias de Cabeça e Pescoço/patologia , Neoplasias de Cabeça e Pescoço/terapia , Humanos , Radioisótopos do Iodo/farmacologia , Masculino , Tumores Neuroendócrinos/patologia , Tumores Neuroendócrinos/terapia , Compostos Organometálicos/farmacologia , Sensibilidade e Especificidade , Estados Unidos , United States Food and Drug Administration
2.
Nat Rev Drug Discov ; 19(9): 589-608, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32728208

RESUMO

Radiopharmaceutical therapy (RPT) is emerging as a safe and effective targeted approach to treating many types of cancer. In RPT, radiation is systemically or locally delivered using pharmaceuticals that either bind preferentially to cancer cells or accumulate by physiological mechanisms. Almost all radionuclides used in RPT emit photons that can be imaged, enabling non-invasive visualization of the biodistribution of the therapeutic agent. Compared with almost all other systemic cancer treatment options, RPT has shown efficacy with minimal toxicity. With the recent FDA approval of several RPT agents, the remarkable potential of this treatment is now being recognized. This Review covers the fundamental properties, clinical development and associated challenges of RPT.


Assuntos
Neoplasias/tratamento farmacológico , Compostos Radiofarmacêuticos/farmacologia , Compostos Radiofarmacêuticos/uso terapêutico , Animais , Aprovação de Drogas/métodos , Humanos , Distribuição Tecidual/fisiologia , Estados Unidos , United States Food and Drug Administration
3.
Sci Rep ; 10(1): 10196, 2020 06 23.
Artigo em Inglês | MEDLINE | ID: mdl-32576907

RESUMO

Peptide receptor radionuclide therapy (PRRT) is an important treatment option for patients with somatostatin receptor-2 (SSTR2)-expressing neuroendocrine tumour (NET) though tumour regression occurs in only a minority of patients. Therefore, novel PRRT regimens with improved therapeutic activity are needed. Radiation induced DNA damage repair is an attractive therapeutic target to increase PRRT efficacy and consequently, we have characterised a panel of preclinical models for their SSTR2 expression, in vivo growth properties and response to 177Lu-DOTA-octreotate (LuTate) PRRT to identify models with features suitable for evaluating novel therapeutic combinations. In vitro studies using the SSTR2 expressing AR42J model demonstrate that the combination of LuTate and the small molecule Poly(ADP-ribose) polymerase-1 (PARP) inhibitor, talazoparib led to increased DNA double strand breaks, as assessed by γ-H2AX foci formation, as compared to LuTate alone. Furthermore, using the AR42J tumour model in vivo we demonstrate that the combination of LuTate and talazoparib significantly improved the anti-tumour efficacy of LuTate alone. These findings support the clinical evaluation of the combination of LuTate and PARP inhibition in SSTR2-expressing NET.


Assuntos
Antineoplásicos/farmacologia , Lutécio/fisiologia , Tumores Neuroendócrinos/tratamento farmacológico , Octreotida/análogos & derivados , Octreotida/farmacologia , Compostos Organometálicos/farmacologia , Poli(ADP-Ribose) Polimerases/metabolismo , Receptores de Somatostatina/metabolismo , Animais , Linhagem Celular Tumoral , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Ftalazinas/farmacologia , Inibidores de Poli(ADP-Ribose) Polimerases/farmacologia , Radioisótopos , Compostos Radiofarmacêuticos/farmacologia
4.
Medicine (Baltimore) ; 99(19): e19989, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32384452

RESUMO

This study aimed to establish an optimal protocol for Tc-sestamibi parathyroid imaging for lesion localization in patients with hyperparathyroidism (HPT).We retrospectively enrolled 35 consecutive patients who underwent dual-phase (at 10 minutes and 120 minutes) Tc-sestamibi parathyroid scintigraphy with single-photon emission computed tomography (SPECT)/computed tomography (CT). Twenty seven patients had primary HPT, and 8 had secondary or tertiary HPT. Three nuclear medicine physicians independently analyzed the parathyroid images for lesion localization at 9 predefined parathyroid locations using the following 4 different image sets blinded to the clinical information:All SPECT or SPECT/CT image sets were analyzed with dual-phase planar images. The image results were compared with the histopathological results after surgery.Dual-phase SPECT/CT showed the highest positive rate of 85.7% in the patient-based analysis and 13.7% in the location-based analysis. Of 35 patients, surgical pathological results were available in 21 (16 adenomas in 16 primary HPTs and 16 hyperplasias in 5 secondary or tertiary HPTs). Dual-phase SPECT/CT showed the sensitivity values of 100% and 84.4% in the patient-based and location-based analysis, respectively, which were the highest sensitivity values among all image sets. In the primary HPT subgroup, dual-phase SPECT/CT showed the highest sensitivity value of 93.8% in the location-based analyses, whereas dual-phase SPECT, early SPECT/CT, and delayed SPECT/CT showed the sensitivity values of 62.5%, 81.3%, and 81.3%, respectively. In the secondary or tertiary HPT subgroup, dual-phase SPECT/CT also showed the highest sensitivity value of 75.0%, whereas early SPECT/CT, delayed SPECT/CT, and dual-phase SPECT showed the sensitivity values of 43.8%, 56.3%, and 68.8%, respectively.Compared with dual-phase SPECT or single-phase SPECT/CT, the dual-phase SPECT/CT imaging protocol for Tc-sestamibi scintigraphy showed the highest positive rate and sensitivity, and was optimal for parathyroid lesion localization.


Assuntos
Hiperparatireoidismo , Hiperplasia , Glândulas Paratireoides/diagnóstico por imagem , Neoplasias das Paratireoides , Cintilografia , Tomografia Computadorizada com Tomografia Computadorizada de Emissão de Fóton Único/métodos , Tecnécio Tc 99m Sestamibi/farmacologia , Feminino , Humanos , Hiperparatireoidismo/diagnóstico , Hiperparatireoidismo/etiologia , Hiperplasia/diagnóstico , Hiperplasia/patologia , Hiperplasia/cirurgia , Masculino , Pessoa de Meia-Idade , Imagem Multimodal/métodos , Neoplasias das Paratireoides/diagnóstico , Neoplasias das Paratireoides/patologia , Neoplasias das Paratireoides/cirurgia , Cintilografia/métodos , Cintilografia/normas , Compostos Radiofarmacêuticos/farmacologia , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
5.
Inorg Chem ; 59(8): 5728-5741, 2020 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-32242663

RESUMO

[44/47Sc]Sc3+, [68Ga]Ga3+, and [111In]In3+ are the three most attractive trivalent smaller radiometalnuclides, offering a wide range of distinct properties (emission energies and types) in the toolbox of nuclear medicine. In this study, all three of the metal ions are successfully chelated using a new oxine-based hexadentate ligand, H3glyox, which forms thermodynamically stable neutral complexes with exceptionally high pM values [pIn (34) > pSc (26) > pGa (24.9)]. X-ray diffraction single crystal structures with stable isotopes revealed that the ligand is highly preorganized and has a perfect fit to size cavity to form [Sc(glyox)(H2O)] and [In(glyox)(H2O)] complexes. Quantitative radiolabeling with gallium-68 (RCY > 95%, [L] = 10-5 M) and indium-111 (RCY > 99%, [L] = 10-8 M) was achieved under ambient conditions (RT, pH 7, and 15 min) with very high apparent molar activities of 750 MBq/µmol and 650 MBq/nmol, respectively. Preliminary quantitative radiolabeling of [44Sc]ScCl3 (RCY > 99%, [L] = 10-6 M) was fast at room temperature (pH 7 and 10 min). In vitro experiments revealed exceptional stability of both [68Ga]Ga(glyox) and [111In]In(glyox) complexes against human serum (transchelation <2%) and its suitability for biological applications. Additionally, on chelation with metal ions, H3glyox exhibits enhanced fluorescence, which was employed to determine the stability constants for Sc(glyox) in addition to the in-batch UV-vis spectrophotometric titrations; as a proof-of-concept these complexes were used to obtain fluorescence images of live HeLa cells using Sc(glyox) and Ga(glyox), confirming the viability of the cells. These initial investigations suggest H3glyox to be a valuable chelator for radiometal-based diagnosis (nuclear and optical imaging) and therapy.


Assuntos
Quelantes/farmacologia , Complexos de Coordenação/farmacologia , Corantes Fluorescentes/farmacologia , Oximas/farmacologia , Compostos Radiofarmacêuticos/farmacologia , Quelantes/síntese química , Complexos de Coordenação/sangue , Complexos de Coordenação/química , Estabilidade de Medicamentos , Corantes Fluorescentes/química , Radioisótopos de Gálio/química , Células HeLa , Humanos , Radioisótopos de Índio/química , Marcação por Isótopo , Ligantes , Microscopia de Fluorescência/métodos , Oximas/síntese química , Estudo de Prova de Conceito , Radioisótopos/química , Compostos Radiofarmacêuticos/sangue , Compostos Radiofarmacêuticos/química , Escândio/química , Termodinâmica
7.
J Med Chem ; 63(9): 4496-4505, 2020 05 14.
Artigo em Inglês | MEDLINE | ID: mdl-32302130

RESUMO

The insertion of single 1,4-disubstituted 1,2,3-triazoles as metabolically stable bioisosteres of trans-amide bonds (triazole scan) was recently applied to the 177Lu-labeled tumor-targeting analog of minigastrin, [Nle15]MG11. The reported novel mono-triazolo-peptidomimetics of [Nle15]MG11 showed either improved resistance against enzymatic degradation or a significantly increased affinity toward the target receptor but never both. To enhance further the tumor-targeting properties of the minigastrin analogs, we studied conjugates with multiple amide-to-triazole substitutions for additive or synergistic effects. Promising candidates were identified by modification of two or three amide bonds, which yielded both improved stability and increased receptor affinity of the peptidomimetics in vitro. Biodistribution studies of radiolabeled multi-triazolo-peptidomimetics in mice bearing receptor-positive tumor xenografts revealed up to 4-fold increased tumor uptake in comparison to the all-amide reference compound [Nle15]MG11. In addition, we report here for the first time a linear peptidomimetic with three triazole insertions in its backbone and maintained biological activity.


Assuntos
Antineoplásicos/farmacologia , Gastrinas/farmacologia , Peptidomiméticos/farmacologia , Compostos Radiofarmacêuticos/farmacologia , Triazóis/farmacologia , Animais , Antineoplásicos/síntese química , Antineoplásicos/metabolismo , Antineoplásicos/farmacocinética , Linhagem Celular Tumoral , Desenho de Fármacos , Gastrinas/síntese química , Gastrinas/metabolismo , Gastrinas/farmacocinética , Humanos , Lutécio/química , Camundongos , Neoplasias/metabolismo , Peptidomiméticos/síntese química , Peptidomiméticos/metabolismo , Peptidomiméticos/farmacocinética , Ligação Proteica , Radioisótopos/química , Compostos Radiofarmacêuticos/síntese química , Compostos Radiofarmacêuticos/metabolismo , Compostos Radiofarmacêuticos/farmacocinética , Receptor de Colecistocinina B/metabolismo , Triazóis/síntese química , Triazóis/metabolismo , Triazóis/farmacocinética
8.
J Med Chem ; 63(9): 4484-4495, 2020 05 14.
Artigo em Inglês | MEDLINE | ID: mdl-32302139

RESUMO

MG11 is a truncated analog of minigastrin, a peptide with high affinity and specificity toward the cholecystokinin-2 receptor (CCK2R), which is overexpressed by different tumors. Thus, radiolabeled MG11 derivatives have great potential for use in cancer diagnosis and therapy. A drawback of MG11 is its fast degradation by proteases, leading to moderate tumor uptake in vivo. We introduced 1,4-disubstituted 1,2,3-triazoles as metabolically stable bioisosteres to replace labile amide bonds of the peptide. The "triazole scan" yielded peptidomimetics with improved resistance to enzymatic degradation and/or enhanced affinity toward the CCK2R. Remarkably, our lead compound achieved a 10-fold increase in receptor affinity, resulting in a 2.6-fold improved tumor uptake in vivo. Modeling of the ligand-CCK2R complex suggests that an additional cation-π interaction of the aromatic triazole moiety with the Arg356 residue of the receptor is accountable for these observations. We show for the first time that the amide-to-triazole substitution strategy offers new opportunities in drug development that go beyond the metabolic stabilization of bioactive peptides.


Assuntos
Antineoplásicos/farmacologia , Gastrinas/farmacologia , Peptidomiméticos/farmacologia , Compostos Radiofarmacêuticos/farmacologia , Triazóis/farmacologia , Animais , Antineoplásicos/síntese química , Antineoplásicos/metabolismo , Antineoplásicos/farmacocinética , Linhagem Celular Tumoral , Feminino , Gastrinas/síntese química , Gastrinas/metabolismo , Gastrinas/farmacocinética , Humanos , Lutécio/química , Camundongos , Neoplasias/metabolismo , Peptidomiméticos/síntese química , Peptidomiméticos/metabolismo , Peptidomiméticos/farmacocinética , Ligação Proteica , Conformação Proteica , Radioisótopos/química , Compostos Radiofarmacêuticos/síntese química , Compostos Radiofarmacêuticos/metabolismo , Compostos Radiofarmacêuticos/farmacocinética , Receptor de Colecistocinina B/metabolismo , Triazóis/síntese química , Triazóis/metabolismo , Triazóis/farmacocinética
9.
PLoS One ; 15(3): e0229859, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32191718

RESUMO

OBJECTIVES: We had developed a method that can help detect and identify lymph nodes affected by the neoplastic process. Our group evaluated the fractal dimension (FD) and X-ray attenuation (XRA) of lymph nodes in HL and compared to their metabolic activity as measured by 18F-FDG-PET examination. METHODS: The training set included 72 lymph nodes from 31 consecutive patients, and the tested set of 71 lymph nodes from next 19 patients. The measurement of FD of each lymph node was performed before the start of therapy using original software. X-ray attenuation (XRA) expressed in HU (Hounsfield Units) from CT scans was compared with the metabolic activity of the lymphatic nodes, measured by 18F-FDG-PET examination. RESULTS: Significant differences were observed between XRAmax and FDmax values in assessing the PET(+) and PET(-) nodes. All nodes were scored from 0 to 2. The HUFRA test properly qualified 95% with a score of 2 and 0 points as PET(+) or PET(-). CONCLUSION: The HUFRA test can differentiate about 70-80% of lymph nodes as PET(+) or PET(-) based solely on the CT examination. It can be useful in patients who were not subjected to 18FFDG-PET/CT examination before the treatment, or who had an unreliable result of 18F-FDG-PET/CT with further research requirements.


Assuntos
Doença de Hodgkin/diagnóstico , Linfonodos/diagnóstico por imagem , Metástase Linfática/diagnóstico , Tomografia por Emissão de Pósitrons , Adolescente , Criança , Feminino , Fluordesoxiglucose F18/farmacologia , Fractais , Doença de Hodgkin/diagnóstico por imagem , Doença de Hodgkin/patologia , Humanos , Linfonodos/patologia , Metástase Linfática/diagnóstico por imagem , Metástase Linfática/patologia , Masculino , Compostos Radiofarmacêuticos/farmacologia
10.
Circ Cardiovasc Imaging ; 13(3): e009889, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32164451

RESUMO

BACKGROUND: The monocyte chemoattractant protein-1/CCR2 (chemokine receptor 2) axis plays an important role in abdominal aortic aneurysm (AAA) pathogenesis, with effects on disease progression and anatomic stability. We assessed the expression of CCR2 in a rodent model and human tissues, using a targeted positron emission tomography radiotracer (64Cu-DOTA-ECL1i). METHODS: AAAs were generated in Sprague-Dawley rats by exposing the infrarenal, intraluminal aorta to PPE (porcine pancreatic elastase) under pressure to induce aneurysmal degeneration. Heat-inactivated PPE was used to generate a sham operative control. Rat AAA rupture was stimulated by the administration of ß-aminopropionitrile, a lysyl oxidase inhibitor. Biodistribution was performed in wild-type rats at 1 hour post tail vein injection of 64Cu-DOTA-ECL1i. Dynamic positron emission tomography/computed tomography imaging was performed in rats to determine the in vivo distribution of radiotracer. RESULTS: Biodistribution showed fast renal clearance. The localization of radiotracer uptake in AAA was verified with high-resolution computed tomography. At day 7 post-AAA induction, the radiotracer uptake (standardized uptake value [SUV]=0.91±0.25) was approximately twice that of sham-controls (SUV=0.47±0.10; P<0.01). At 14 days post-AAA induction, radiotracer uptake by either group did not significantly change (AAA SUV=0.86±0.17 and sham-control SUV=0.46±0.10), independent of variations in aortic diameter. Competitive CCR2 receptor blocking significantly decreased AAA uptake (SUV=0.42±0.09). Tracer uptake in AAAs that subsequently ruptured (SUV=1.31±0.14; P<0.005) demonstrated uptake nearly twice that of nonruptured AAAs (SUV=0.73±0.11). Histopathologic characterization of rat and human AAA tissues obtained from surgery revealed increased expression of CCR2 that was co-localized with CD68+ macrophages. Ex vivo autoradiography demonstrated specific binding of 64Cu-DOTA-ECL1i to CCR2 in both rat and human aortic tissues. CONCLUSIONS: CCR2 positron emission tomography is a promising new biomarker for the noninvasive assessment of AAA inflammation that may aid in associated rupture prediction.


Assuntos
Aneurisma Roto/diagnóstico , Aorta Abdominal/diagnóstico por imagem , Aneurisma da Aorta Abdominal/diagnóstico , Regulação da Expressão Gênica , Tomografia por Emissão de Pósitrons/métodos , Receptores CCR2/genética , Aneurisma Roto/genética , Aneurisma Roto/metabolismo , Animais , Aorta Abdominal/metabolismo , Aneurisma da Aorta Abdominal/genética , Aneurisma da Aorta Abdominal/metabolismo , Biomarcadores/metabolismo , Fluordesoxiglucose F18/farmacologia , Masculino , Prognóstico , RNA/genética , Compostos Radiofarmacêuticos/farmacologia , Ratos , Ratos Sprague-Dawley , Receptores CCR2/biossíntese
11.
Eur Radiol ; 30(5): 2443-2453, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32034487

RESUMO

OBJECTIVES: To compare the diagnostic accuracy of preoperative 18F-FDG PET/CT and MRI tumor markers for prediction of lymph node metastases (LNM) and aggressive disease in endometrial cancer (EC). METHODS: Preoperative whole-body 18F-FDG PET/CT and pelvic MRI were performed in 215 consecutive patients with histologically confirmed EC. PET/CT-based tumor standardized uptake value (SUVmax and SUVmean), metabolic tumor volume (MTV), and PET-positive lymph nodes (LNs) (SUVmax > 2.5) were analyzed together with the MRI-based tumor volume (VMRI), mean apparent diffusion coefficient (ADCmean), and MRI-positive LN (maximum short-axis diameter ≥ 10 mm). Imaging parameters were explored in relation to surgicopathological stage and tumor grade. Receiver operating characteristic (ROC) curves were generated yielding optimal cutoff values for imaging parameters, and regression analyses were used to assess their diagnostic performance for prediction of LNM and progression-free survival. RESULTS: For prediction of LNM, MTV yielded the largest area under the ROC curve (AUC) (AUC = 0.80), whereas VMRI had lower AUC (AUC = 0.72) (p = 0.03). Furthermore, MTV > 27 ml yielded significantly higher specificity (74%, p < 0.001) and accuracy (75%, p < 0.001) and also higher odds ratio (12.2) for predicting LNM, compared with VMRI > 10 ml (58%, 62%, and 9.7, respectively). MTV > 27 ml also tended to yield higher sensitivity than PET-positive LN (81% vs 50%, p = 0.13). Both VMRI > 10 ml and MTV > 27 ml were significantly associated with reduced progression-free survival. CONCLUSIONS: Tumor markers from 18F-FDG PET/CT outperform MRI markers for the prediction of LNM. MTV > 27 ml yields a high diagnostic performance for predicting aggressive disease and represents a promising supplement to conventional PET/CT reading in EC. KEY POINTS: • Metabolic tumor volume (MTV) outperforms other 18F-FDG PET/CT and MRI markers for preoperative prediction of lymph node metastases (LNM) in endometrial cancer patients. • Using cutoff values for tumor volume for prediction of LNM, MTV > 27 ml yielded higher specificity and accuracy than VMRI> 10 ml. • MTV represents a promising supplement to conventional PET/CT reading for predicting aggressive disease in EC.


Assuntos
Neoplasias do Endométrio/diagnóstico , Fluordesoxiglucose F18/farmacologia , Linfonodos/diagnóstico por imagem , Imagem por Ressonância Magnética/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias do Endométrio/secundário , Feminino , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons/métodos , Tomografia por Emissão de Pósitrons/métodos , Curva ROC , Compostos Radiofarmacêuticos/farmacologia
13.
Eur Radiol ; 30(5): 2435-2442, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32002639

RESUMO

OBJECTIVE: To evaluate the imaging features of hepatic epithelioid hemangioendothelioma (HEH) on multiphasic CT, MR, and FDG-PET-CT. METHODS: Bi-institutional review identified 67 adults (mean age, 47 years; 23 M/44 F) with pathologically proven HEH and pretreatment multiphasic CT (n = 67) and/or MR (n = 30) and/or FDG-PET-CT (n = 13). RESULTS: HEHs were multifocal in 88% (59/67). Mean size of the dominant mass was 4.1 cm (range, 1.4-19 cm). The tumors were located in the peripheral, subcapsular regions of the liver in 96% (64/67). Capsular retraction was present in 81% (54/67 cases) and tumors were coalescent in 61% (41/67). HEH demonstrated peripheral ring enhancement on arterial phase imaging in 33% (21/64) and target appearance on the portal venous phase in 69% (46/67). Persistent peripheral enhancement on the delayed phase was seen in 49% (31/63). On MR, multilayered target appearance was seen on the T2-weighted sequences in 67% (20/30) and on the diffusion-weighted sequences in 61% (11/18). Target appearance on hepatobiliary phase of MRI was seen in 57% (4/7). On pre-therapy FDG-PET-CT, increased FDG uptake above the background liver parenchyma was seen in 62% (8/13). CONCLUSION: HEHs typically manifest as multifocal, coalescent hepatic nodules in peripheral subcapsular location, with associated capsular retraction. Peripheral arterial ring enhancement and target appearance on portal venous phase are commonly seen on CT. Similarly, multilayered target appearance correlating with its histopathological composition is typically seen on multiple sequences of MR including T2-weighted, diffusion-weighted, and dynamic contrast-enhanced multiphasic MR. KEY POINTS: • Hepatic epithelioid hemangioendotheliomas manifest on CT and MR as multifocal, coalescent hepatic nodules in peripheral subcapsular location, with associated capsular retraction. • Enhancement pattern on contrast-enhanced CT and MR can vary but peripheral ring enhancement on arterial phase and target appearance on portal venous phase are commonly seen. • Retrospective two-center study showed that cross-sectional imaging may help in the diagnosis.


Assuntos
Fluordesoxiglucose F18/farmacologia , Hemangioendotelioma Epitelioide/diagnóstico , Neoplasias Hepáticas/diagnóstico , Imagem por Ressonância Magnética/métodos , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Compostos Radiofarmacêuticos/farmacologia , Estudos Retrospectivos , Adulto Jovem
14.
Interact Cardiovasc Thorac Surg ; 30(4): 593-596, 2020 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-32003806

RESUMO

Although 18F-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) scan has been generally validated in the staging of malignant pleural mesothelioma (MPM), its diagnostic and prognostic performances are not clearly established. Aiming to identify possible factors causing 18F-fluorodeoxyglucose PET/CT false-negative results and influencing prognosis in MPM patients, we analysed clinical, radiometabolic and pathological features in 141 MPM patients who underwent diagnostic 18F-fluorodeoxyglucose PET/CT scan (January 2009-July 2018) at 2 high-volume institutions. The Fisher's exact test and the Cox model were used in statistical analysis. Overall detection rate was 88.3% with 16 patients (11.6%) presenting with a standardized uptake value (SUV) max <2.5 (PET-negative). PET-negative cases were more frequently detected in older patients (P = 0.027) and early-stage tumours (33.3% false-negative in stage I and 40.0% false-negative in T1-tumours, with P = 0.014 both). Mean SUVmax value was higher in sarcomatoid (11.8 ± 4.6) and biphasic MPM (9.3 ± 7.0), rather than in epithelioid MPM (6.9 ± 3.8, P < 0.001). Concerning overall survival, SUVmax (both as continuous and as categorical variable) was found to be a prognostic factor, in addition to stage (P = 0.032) and histology (P = 0.014) as confirmed by multivariable analysis (hazard ratio 2.65, confidence interval 1.23-5.70; P < 0.001). In the light of such results, we highlight that a low fluorodeoxyglucose uptake might be observed in more than 10% MPMs, especially in early-stage tumours affecting elderly patients. Furthermore, high SUVmax values significantly correlated with a worse prognosis.


Assuntos
Fluordesoxiglucose F18/farmacologia , Neoplasias Pulmonares/diagnóstico , Mesotelioma/diagnóstico , Estadiamento de Neoplasias/métodos , Neoplasias Pleurais/diagnóstico , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons/métodos , Idoso , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Prognóstico , Compostos Radiofarmacêuticos/farmacologia , Reprodutibilidade dos Testes
16.
Int J Mol Sci ; 21(4)2020 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-32075258

RESUMO

Human epidermal growth factor receptor type 3 (HER3) is an emerging therapeutic target in several malignancies. To select potential responders to HER3-targeted therapy, radionuclide molecular imaging of HER3 expression using affibody molecules could be performed. Due to physiological expression of HER3 in normal organs, high imaging contrast remains challenging. Due to slow internalization of affibody molecules by cancer cells, we hypothesized that labeling (HE)3-ZHER3:08698-DOTAGA affibody molecule with non-residualizing [125I]-N-succinimidyl-4-iodobenzoate (PIB) label would improve the tumor-to-normal organs ratios compared to previously reported residualizing radiometal labels. The [125I]I-PIB-(HE)3-ZHER3:08698-DOTAGA was compared side-by-side with [111In]In-(HE)3-ZHER3:08698-DOTAGA. Both conjugates demonstrated specific high-affinity binding to HER3-expressing BxPC-3 and DU145 cancer cells. Biodistribution in mice bearing BxPC-3 xenografts at 4 and 24 h pi showed faster clearance of the [125I]I-PIB label compared to the indium-111 label from most tissues, except blood. This resulted in higher tumor-to-organ ratios in HER3-expressing organs for [125I]I-PIB-(HE)3-ZHER3:08698-DOTAGA at 4 h, providing the tumor-to-liver ratio of 2.4 ± 0.3. The tumor uptake of both conjugates was specific, however, it was lower for the [125I]I-PIB label. In conclusion, the use of non-residualizing [125I]I-PIB label for HER3-targeting affibody molecule provided higher tumor-to-liver ratio than the indium-111 label, however, further improvement in tumor uptake and retention is needed.


Assuntos
Regulação Neoplásica da Expressão Gênica/efeitos da radiação , Radioisótopos/farmacologia , Receptor ErbB-3/isolamento & purificação , Distribuição Tecidual/efeitos da radiação , Animais , Linhagem Celular Tumoral , Xenoenxertos , Humanos , Radioisótopos de Índio/química , Radioisótopos do Iodo/química , Marcação por Isótopo , Camundongos , Imagem Molecular/métodos , Compostos Radiofarmacêuticos/farmacologia , Receptor ErbB-3/genética
17.
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
18.
Circ Cardiovasc Imaging ; 13(2): e010249, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-32063053

RESUMO

BACKGROUND: Technetium-99 m pyrophosphate protocols for transthyretin cardiac amyloidosis diagnosis have variably used 1- and 3-hour imaging time points. We investigated whether imaging at 1 hour with superior efficiency had comparable diagnostic accuracy as 3-hour imaging. METHODS: This is a registry analysis of patients with suspected transthyretin cardiac amyloidosis referred for technetium-99 m pyrophosphate at a single tertiary center from June 2015 through January 2019. Patients underwent planar and single-photon emission computed tomography (SPECT) imaging at 1 and 3 hours. A positive Tc-99m pyrophosphate study was defined by the presence of diffuse myocardial tracer uptake on SPECT. For planar imaging, visual semiquantitative (grades 0-3, ≥2 considered positive) and quantitative heart to contralateral ratios (≥1.5 considered positive) were used. RESULTS: Two hundred thirty-three patients (69% men; median age, 77 [69-83] years) underwent the study protocol. There were 60 (25.8%) patients with diffuse myocardial uptake, 1 (0.4%) with regional uptake, and 172 (73.8%) with no myocardial uptake. Results of SPECT were identical at 1 and 3 hours. Planar imaging at 1 hour had 98% sensitivity and 96% specificity. Planar grade 0 uptake or heart to contralateral ratio ≤1.2 and planar grade 3 uptake or heart to contralateral ratio ≥2.0 were always associated with negative and positive SPECT, respectively. For planar grades 1 and 2 uptake and heart to contralateral ratio 1.3 to 1.9, SPECT was needed to make a diagnosis. No patient with light-chain cardiac amyloidosis had positive SPECT. CONCLUSIONS: An efficient 1-hour technetium-99 m pyrophosphate protocol had comparable diagnostic performance to a 3-hour protocol.


Assuntos
Neuropatias Amiloides Familiares/diagnóstico , Cardiomiopatias/diagnóstico , Pirofosfato de Tecnécio Tc 99m/farmacologia , Tomografia Computadorizada de Emissão de Fóton Único/métodos , Idoso , Idoso de 80 Anos ou mais , Diagnóstico Diferencial , Feminino , Seguimentos , Humanos , Masculino , Compostos Radiofarmacêuticos/farmacologia , Reprodutibilidade dos Testes , Estudos Retrospectivos , Fatores de Tempo
19.
Eur Radiol ; 30(6): 3310-3323, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32060716

RESUMO

INTRODUCTION: A systematic review and meta-analysis were performed to determine the diagnostic performance of dynamic contrast-enhanced computed tomography (DCE-CT) for the differentiation between malignant and benign pulmonary nodules. METHODS: Ovid MEDLINE and EMBASE were searched for studies published up to October 2018 on the diagnostic accuracy of DCE-CT for the characterisation of pulmonary nodules. For the index test, studies with a minimum of a pre- and post-contrast computed tomography scan were evaluated. Studies with a reference standard of biopsy for malignancy, and biopsy or 2-year follow-up for benign disease were included. Study bias was assessed using QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies). The sensitivities, specificities, and diagnostic odds ratios were determined along with 95% confidence intervals (CIs) using a bivariate random effects model. RESULTS: Twenty-three studies were included, including 2397 study participants with 2514 nodules of which 55.3% were malignant (1389/2514). The pooled accuracy results were sensitivity 94.8% (95% CI 91.5; 96.9), specificity 75.5% (69.4; 80.6), and diagnostic odds ratio 56.6 (24.2-88.9). QUADAS 2 assessment showed intermediate/high risk of bias in a large proportion of the studies (52-78% across the domains). No difference was present in sensitivity or specificity between subgroups when studies were split based on CT technique, sample size, nodule size, or publication date. CONCLUSION: DCE-CT has a high diagnostic accuracy for the diagnosis of pulmonary nodules although study quality was indeterminate in a large number of cases. KEY POINTS: • The pooled accuracy results were sensitivity 95.1% and specificity 73.8% although individual studies showed wide ranges of values. • This is comparable to the results of previous meta-analyses of PET/CT (positron emission tomography/computed tomography) diagnostic accuracy for the diagnosis of solitary pulmonary nodules. • Robust direct comparative accuracy and cost-effectiveness studies are warranted to determine the optimal use of DCE-CT and PET/CT in the diagnosis of SPNs.


Assuntos
Fluordesoxiglucose F18/farmacologia , Neoplasias Pulmonares/diagnóstico , Nódulos Pulmonares Múltiplos/diagnóstico , Nódulo Pulmonar Solitário/diagnóstico , Tomografia Computadorizada por Raios X/métodos , Humanos , Compostos Radiofarmacêuticos/farmacologia
20.
Org Biomol Chem ; 18(13): 2387-2391, 2020 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-32073113

RESUMO

Dihydromethidine (DHM) labeled with 18F at the para position of the peripheral benzene ring was designed as a positron emission tomography (PET) radiotracer for non-invasive imaging of reactive oxygen species (ROS). This compound readily crosses the blood-brain barrier and is oxidized by ROS, and the oxidation product is retained intracellularly. PET imaging of ROS-producing rat brain microinfused with sodium nitroprusside identified specific brain regions with high ROS concentrations. This tracer should be useful for studies of the pathophysiological roles of ROS, and in the diagnosis of neurodegenerative diseases.


Assuntos
Encéfalo/diagnóstico por imagem , Fenantridinas/farmacologia , Compostos Radiofarmacêuticos/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Animais , Encéfalo/metabolismo , Encéfalo/patologia , Radioisótopos de Flúor/química , Inflamação/induzido quimicamente , Inflamação/diagnóstico por imagem , Inflamação/patologia , Nitroprussiato , Oxirredução , Fenantridinas/síntese química , Fenantridinas/farmacocinética , Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos/síntese química , Compostos Radiofarmacêuticos/farmacocinética , Ratos
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