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1.
Molecules ; 26(5)2021 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-33800801

RESUMO

Diabetes remains one of the fastest growing chronic diseases and is a leading source of morbidity and accelerated mortality in the world. Loss of beta cell mass (BCM) and decreased sensitivity to insulin underlie diabetes pathogenesis. Yet, the ability to safely and directly assess BCM in individuals with diabetes does not exist. Measures such as blood glucose provide only a crude indirect picture of beta cell health. PET imaging could, in theory, allow for safe, direct, and precise characterization of BCM. However, identification of beta cell-specific radiolabeled tracers remains elusive. G-protein coupled receptor 44 (GPR44) is a transmembrane protein that was characterized in 2012 as highly beta cell-specific within the insulin-positive islets of Langerhans. Accordingly, radiolabeling of existing GPR44 antagonists could be a viable method to accelerate PET tracer development. The present study aims to evaluate and summarize published analogues of the GPR44 antagonist ramatroban to develop 18F-labeled PET tracers for BCM analysis. The 77 corresponding ramatroban analogues containing a fluorine nuclide were characterized for properties including binding affinity, selectivity, and pharmacokinetic and metabolic profile, and 32 compounds with favorable properties were identified. This review illustrates the potential of GPR44 analogues for the development of PET tracers.


Assuntos
Carbazóis/química , Radioisótopos de Flúor/metabolismo , Células Secretoras de Insulina/metabolismo , Tomografia por Emissão de Pósitrons/métodos , Traçadores Radioativos , Compostos Radiofarmacêuticos/metabolismo , Receptores Imunológicos/metabolismo , Receptores de Prostaglandina/metabolismo , Sulfonamidas/química , Humanos , Células Secretoras de Insulina/química , Células Secretoras de Insulina/citologia , Inibidores da Agregação Plaquetária/química
2.
Molecules ; 26(8)2021 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-33921765

RESUMO

INTRODUCTION: Benzodiazepines, including temazepam are described as TSPO antagonists. In fact, TSPO was initially described as a peripheral benzodiazepine receptor (PBR) with a secondary binding site for diazepam. TSPO is a potential imaging target of neuroinflammation because there is an amplification of the expression of this receptor. OBJECTIVES: Herein, we developed a novel fluorinated benzodiazepine ligand, [18F]Fluoroethyltemazepam ([18F]F-FETEM), for positron emission tomography (PET) imaging of translocator protein (18 kDa). METHODS: [18F]F-FETEM was radiolabelled with an automated synthesizer via a one-pot procedure. We conducted a [18F]F-aliphatic nucleophilic substitution of a tosylated precursor followed by purification on C18 and Alumina N SPE cartridges. Quality control tests was also carried out. RESULTS: We obtained 2.0-3.0% decay-uncorrected radiochemical activity yield (3.7% decay-corrected) within the whole synthesis time about 33 min. The radiochemical purity of [18F]F-FETEM was over 90% by TLC analysis. CONCLUSIONS: This automated procedure may be used as basis for future production of [18F]F-FETEM for preclinical PET imaging studies.


Assuntos
Radioisótopos de Flúor/análise , Tomografia por Emissão de Pósitrons/métodos , Animais , Benzodiazepinas/análise , Compostos Radiofarmacêuticos
3.
Eur J Endocrinol ; 185(1): 109-120, 2021 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-33886494

RESUMO

Background: Primary hyperparathyroidism is characterized by an autonomous hypersecretion of parathyroid hormone by one or more parathyroid glands. Preoperative localization of the affected gland(s) is of key importance in order to allow minimally invasive surgery. At the moment, 11C-Methionine and 18F-Fluorocholine PET studies appear to be among the most promising second-line localization techniques; their comparative diagnostic performance, however, is still unknown. Methods: PubMed/Medline and Embase databases were searched up to October 2020 for studies estimating the diagnostic accuracy of 11C-Methionine PET or 18F-Fluorocholine PET for parathyroid localization in patients with primary hyperparathyroidism. Pooled sensitivity and positive predictive value were calculated for each tracer on a 'per-lesion' basis and compared using a random-effect model subgroup analysis. Results: In total, 22Twenty-two studies were finally considered in the meta-analysis. Of these, 8 evaluated the diagnostic accuracy of 11C-Methionine and 14 that of 18F-Fluorocholine. No study directly comparing the two tracers was found. The pooled sensitivity of 18F-Fluorocholine was higher than that of 11C-Methionine (92% vs 80%, P < 0.01), while the positive predictive value was similar (94% vs 95%, P = 0.99). These findings were confirmed in multivariable meta-regression models, demonstrating their apparent independence from other possible predictors or confounders at a study level. Conclusion: This was the first meta-analysis that specifically compared the diagnostic accuracy of 11C-Methionine and 18F-Fluorocholine PET for parathyroid localization in patients with primary hyperparathyroidism. Our results suggested a superior performance of 18F-Fluorocholine in terms of sensitivity, while the two tracers had comparable accuracy in terms of positive predictive value.


Assuntos
Adenoma/diagnóstico por imagem , Colina/análogos & derivados , Hiperparatireoidismo Primário/diagnóstico por imagem , Metionina , Neoplasias das Paratireoides/diagnóstico por imagem , Tomografia por Emissão de Pósitrons/métodos , Adenoma/cirurgia , Radioisótopos de Carbono , Radioisótopos de Flúor , Humanos , Hiperparatireoidismo Primário/cirurgia , Procedimentos Cirúrgicos Minimamente Invasivos , Neoplasias das Paratireoides/cirurgia , Paratireoidectomia , Cuidados Pré-Operatórios
4.
Methods Mol Biol ; 2265: 407-416, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33704730

RESUMO

Melanin exists in the most of melanoma lesions. Melanin plays an important role in melanoma progression, metastasis, therapy response, and the overall survival of patients. Therefore, melanin is a critical target for melanoma diagnosis and therapy. Many melanin targeting probes, such as radioisotope-labeled benzamide analogs, have been developed for melanoma diagnosis using positron emission tomography (PET). The N-(2-(diethylamino)-ethyl)-18F-5-fluoropicolinamide (18F-P3BZA) probe is one of the benzamide analogs and has been preliminarily tested for clinical diagnosis of melanoma in our recent studies. It has shown high specificity and favorable in vivo performance for PET of melanoma. Herein, we describe the detailed synthesis protocol of 18F-P3BZA and PET/CT imaging procedure for animal models and patients.


Assuntos
Radioisótopos de Flúor , Melaninas/metabolismo , Melanoma Experimental , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Compostos Radiofarmacêuticos , Animais , Radioisótopos de Flúor/química , Radioisótopos de Flúor/farmacologia , Melanoma Experimental/diagnóstico , Melanoma Experimental/metabolismo , Camundongos , Compostos Radiofarmacêuticos/síntese química , Compostos Radiofarmacêuticos/química , Compostos Radiofarmacêuticos/farmacologia
5.
Medicine (Baltimore) ; 100(12): e25165, 2021 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-33761691

RESUMO

RATIONALE: Rosai-Dorfman disease (RDD) is a rare and self-limiting condition caused by the non-neoplastic proliferation of histiocytes/phagocytes in the sinusoids of lymph nodes and in extranodal tissues. Of the extranodal involvement, laryngeal involvement is extremely rare. Because of its rarity and nonspecific clinicoradiologic features, RDD is often difficult to differentiate from other benign or malignant lymphoproliferative diseases. We present a case of RDD with infiltration of IgG4-bearing plasma cells manifesting laryngeal and nasal masses with cervical lymphadenopathy. PATIENT CONCERNS: A 45-year-old male patient presented with recurrent epistaxis and airway disturbance. DIAGNOSES: On endoscopy, there were submucosal masses in both nasal cavities and both sides of subglottic larynx. On neck CT, there were well-defined, enhancing soft tissue masses in both nasal cavities and both sides of subglottic larynx, resulting in mild airway narrowing. In addition, multiple enlarged lymph nodes showing homogeneous enhancement were noted in both parotid glands and both internal jugular chains. All lesions demonstrated marked FDG-uptake on PET/CT. Therefore, the initial radiologic differential diagnoses included lymphoma and IgG4-related disease. Biopsy was performed on the nasal and laryngeal lesions, and they revealed RDD with infiltration of IgG4-bearing plasma cells. INTERVENTION: The patient underwent surgical resection of the masses in the nasal cavity and larynx to relieve airway narrowing. OUTCOMES: After surgery, airway obstruction was much improved and the patient was asymptomatic. On outpatient follow-up, he exhibited a stable condition and had no dyspnea on exercise. LESSONS: Clinical awareness and suspicion are important for the accurate diagnosis and management of patients with homogeneous masses in the larynx or nasal cavity, even if there is no combined cervical lymphadenopathy.


Assuntos
Histiocitose Sinusal/imunologia , Histiocitose Sinusal/patologia , Imunoglobulina G/imunologia , Laringe/patologia , Linfadenopatia/patologia , Cavidade Nasal/patologia , Plasmócitos/imunologia , Obstrução das Vias Respiratórias/etiologia , Obstrução das Vias Respiratórias/cirurgia , Biópsia , Diagnóstico Diferencial , Endoscopia , Epistaxe/etiologia , Radioisótopos de Flúor , Histiocitose Sinusal/complicações , Histiocitose Sinusal/cirurgia , Humanos , Laringe/cirurgia , Linfadenopatia/etiologia , Linfadenopatia/cirurgia , Masculino , Pessoa de Meia-Idade , Cavidade Nasal/cirurgia , Pescoço , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Recidiva
6.
Int J Mol Sci ; 22(5)2021 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-33669003

RESUMO

The adenosine A2A receptor (A2AR) represents a potential therapeutic target for neurodegenerative diseases. Aiming at the development of a positron emission tomography (PET) radiotracer to monitor changes of receptor density and/or occupancy during the A2AR-tailored therapy, we designed a library of fluorinated analogs based on a recently published lead compound (PPY). Among those, the highly affine 4-fluorobenzyl derivate (PPY1; Ki(hA2AR) = 5.3 nM) and the 2-fluorobenzyl derivate (PPY2; Ki(hA2AR) = 2.1 nM) were chosen for 18F-labeling via an alcohol-enhanced copper-mediated procedure starting from the corresponding boronic acid pinacol ester precursors. Investigations of the metabolic stability of [18F]PPY1 and [18F]PPY2 in CD-1 mice by radio-HPLC analysis revealed parent fractions of more than 76% of total activity in the brain. Specific binding of [18F]PPY2 on mice brain slices was demonstrated by in vitro autoradiography. In vivo PET/magnetic resonance imaging (MRI) studies in CD-1 mice revealed a reasonable high initial brain uptake for both radiotracers, followed by a fast clearance.


Assuntos
Encéfalo/diagnóstico por imagem , Radioisótopos de Flúor/química , Hidrocarbonetos Fluorados/química , Tomografia por Emissão de Pósitrons/métodos , Compostos Radiofarmacêuticos/química , Receptor A2A de Adenosina/metabolismo , Adenosina/metabolismo , Antagonistas do Receptor A2 de Adenosina/química , Animais , Autorradiografia , Encéfalo/metabolismo , Cromatografia Líquida de Alta Pressão , Cricetinae , Hidrocarbonetos Fluorados/síntese química , Imageamento por Ressonância Magnética , Camundongos , Simulação de Acoplamento Molecular , Relação Estrutura-Atividade
7.
J Med Chem ; 64(6): 3462-3478, 2021 03 25.
Artigo em Inglês | MEDLINE | ID: mdl-33705656

RESUMO

The transamidase activity of transglutaminase 2 (TGase 2) is considered to be important for several pathophysiological processes including fibrotic and neoplastic tissue growth, whereas in healthy cells this enzymatic function is predominantly latent. Methods that enable the highly sensitive detection of TGase 2, such as application of radiolabeled activity-based probes, will support the exploration of the enzyme's function in various diseases. In this context, the radiosynthesis and detailed in vitro radiopharmacological evaluation of an 18F-labeled Nε-acryloyllysine piperazide are reported. Robust and facile detection of the radiotracer-TGase 2 complex by autoradiography of thin layer plates and polyacrylamide gels after chromatographic and electrophoretic separation owing to irreversible covalent bond formation was demonstrated for the isolated protein, cell lysates, and living cells. By use of this radiotracer, quantitative data on the expression profile of activatable TGase 2 in mouse organs and selected tumors were obtained for the first time by autoradiography of tissue sections.


Assuntos
Radioisótopos de Flúor/química , Proteínas de Ligação ao GTP/análise , Lisina/análogos & derivados , Piperazinas/química , Transglutaminases/análise , Animais , Linhagem Celular Tumoral , Proteínas de Ligação ao GTP/antagonistas & inibidores , Humanos , Lisina/síntese química , Camundongos , Neoplasias/enzimologia , Neoplasias/patologia , Piperazinas/síntese química , Transglutaminases/antagonistas & inibidores
8.
J Med Chem ; 64(7): 4179-4195, 2021 04 08.
Artigo em Inglês | MEDLINE | ID: mdl-33783213

RESUMO

The prostate-specific membrane antigen (PSMA) is considered to be an excellent theranostic target of prostate cancer (PCa). In this study, three 18F-labeled PSMA tracers with a more lipophilic quinoline functional spacer were designed, synthesized, and evaluated based on the Glu-Ureido-Lys binding motif. The effect of structure-related lipophilic difference on distribution and excretion of these tracers in vitro and in vivo (cells, rodent, primate, and human) was investigated by comparing with [18F]DCFPyL. There is no significant correlation between the renal elimination and the lipophilicity of the tracers in all species. However, the higher the lipophilicity of tracer, the higher the radioactivity accumulation in the liver of primate and human, and the less radioactivity is to excrete to the bladder with urine. The screened tracer [18F]8c, with a Ki value of 4.58 nM, displayed notable low bladder retention and demonstrated good imaging properties in patients with PCa.


Assuntos
Antígenos de Superfície/metabolismo , Meios de Contraste/química , Glutamato Carboxipeptidase II/metabolismo , Neoplasias da Próstata/diagnóstico por imagem , Quinolinas/química , Compostos Radiofarmacêuticos/química , Ureia/análogos & derivados , Animais , Linhagem Celular Tumoral , Meios de Contraste/síntese química , Radioisótopos de Flúor/química , Humanos , Macaca fascicularis , Masculino , Camundongos Endogâmicos ICR , Tomografia por Emissão de Pósitrons , Neoplasias da Próstata/metabolismo , Quinolinas/síntese química , Quinolinas/urina , Compostos Radiofarmacêuticos/síntese química , Compostos Radiofarmacêuticos/urina , Eliminação Renal , Ureia/síntese química , Ureia/urina
9.
Ann Hematol ; 100(4): 1039-1047, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33634350

RESUMO

Extranodal natural killer/T-cell lymphoma, nasal-type (ENKTL) is a type of rare and distinct entity of non-Hodgkin lymphoma with poor prognosis. It is important to evaluate the early treatment response accurately to decide further treatment strategy. 18F-FDG PET/CT plays an important role in response evaluation and prognostic prediction in some kinds of lymphomas. However, data available regarding patients with ENKTL are limited. Thus, in this prospective study, we analyzed the prognostic value of 18F-FDG PET/CT in ENKTL. Thirty-four patients with newly diagnosed ENKTL were enrolled in this phase 2 study (NCT02825147, July 7, 2016). The patients received pre-, mid-, and end-treatment 18F-FDG PET/CT scans. Deauville score (DS), maximal standardized uptake values (SUVmax), and the change in SUVmax (ΔSUVmax) were recorded for response assessment. The median follow-up period was 42.2 months. The 2-year overall survival (OS) and progression-free survival (PFS) were 82.4% and 73.5%, respectively. Univariate analysis revealed that Ann Arbor stage (P < 0.002), mid-treatment DS (P = 0.005), mid-SUVmax (P = 0.001), mid-∆SUVmax (P = 0.004), end-treatment DS (P < 0.001), and end-SUVmax (P = 0.014) were prognostic factors for OS. Ann Arbor stage (P = 0.001), mid-treatment DS (P = 0.008), mid-SUVmax (P = 0.029), mid-∆SUVmax (P < 0.001), and end-treatment DS (P =0.021) were of prognostic significance for PFS. Multivariate analysis showed that mid-SUVmax (P = 0.042) and DS at the middle (P = 0.050) and end (P = 0.044) of treatment were significant independent predictors of PFS. 18F-FDG PET/CT is useful for predicting the prognosis of ENKTL.


Assuntos
Linfoma Extranodal de Células T-NK/diagnóstico por imagem , Cavidade Nasal , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Adolescente , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Asparaginase/administração & dosagem , Dexametasona/administração & dosagem , Etoposídeo/administração & dosagem , Feminino , Radioisótopos de Flúor , Fluordesoxiglucose F18 , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Linfoma Extranodal de Células T-NK/tratamento farmacológico , Linfoma Extranodal de Células T-NK/mortalidade , Linfoma Extranodal de Células T-NK/radioterapia , Masculino , Metotrexato/administração & dosagem , Pessoa de Meia-Idade , Polietilenoglicóis/administração & dosagem , Prognóstico , Intervalo Livre de Progressão , Modelos de Riscos Proporcionais , Estudos Prospectivos , Compostos Radiofarmacêuticos , Radioterapia de Alta Energia , Sensibilidade e Especificidade , Adulto Jovem
10.
Br J Radiol ; 94(1120): 20210043, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33571003

RESUMO

OBJECTIVE: A new Bayesian penalized likelihood reconstruction algorithm for positron emission tomography (PET) (Q.Clear) is now in clinical use for fludeoxyglucose (FDG) PET/CT. However, experience with non-FDG tracers and in special patient populations is limited. This pilot study aims to compare Q.Clear to standard PET reconstructions for 18F sodium fluoride (18F-NaF) PET in obese patients. METHODS: 30 whole body 18F-NaF PET/CT scans (10 patients with BMI 30-40 Kg/m2 and 20 patients with BMI >40 Kg/m2) and a NEMA image quality phantom scans were analyzed using ordered subset expectation maximization (OSEM) and Q.Clear reconstructions methods with B400, 600, 800 and 1000. The images were assessed for overall image quality (IQ), noise level, background soft tissue, and lesion detectability, contrast recovery (CR), background variability (BV) and contrast-to-noise ratio (CNR) for both algorithms. RESULTS: CNR for clinical cases was higher for Q.Clear than OSEM (p < 0.05). Mean CNR for OSEM was (21.62 ± 8.9), and for Q.Clear B400 (31.82 ± 14.6), B600 (35.54 ± 14.9), B800 (39.81 ± 16.1), and B1000 (40.9 ± 17.8). As the ß value increased the CNR increased in all clinical cases. B600 was the preferred ß value for reconstruction in obese patients. The phantom study showed Q.Clear reconstructions gave lower CR and lower BV than OSEM. The CNR for all spheres was significantly higher for Q.Clear (independent of ß) than OSEM (p < 0.05), suggesting superiority of Q.Clear. CONCLUSION: This pilot clinical study shows that Q.Clear reconstruction algorithm improves overall IQ of 18F-NaF PET in obese patients. Our clinical and phantom measurement results demonstrate improved CNR and reduced BV when using Q.Clear. A ß value of 600 is preferred for reconstructing 18F-NaF PET/CT with Q.Clear in obese patients. ADVANCES IN KNOWLEDGE: 18F-NaF PET/CT is less susceptible to artifacts induced by body habitus. Bayesian penalized likelihood reconstruction with18F-NaF PET improves overall IQ in obese patients.


Assuntos
Neoplasias Ósseas/diagnóstico por imagem , Radioisótopos de Flúor , Interpretação de Imagem Assistida por Computador/métodos , Obesidade/complicações , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Fluoreto de Sódio , Algoritmos , Teorema de Bayes , Neoplasias Ósseas/complicações , Neoplasias Ósseas/secundário , Osso e Ossos/diagnóstico por imagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Imagem Corporal Total/métodos
11.
Eur J Med Chem ; 214: 113245, 2021 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-33582389

RESUMO

18F-Labelled pyrrolopyrimidines were synthesized and evaluated as positron emission tomography (PET) probes to determine leucine-rich repeat kinase 2 (LRRK2) expression in the brain. With pyrrolopyrimidine derivative PF-06447475 as the lead compound, two in vivo-stable 18F-labelled pyrrolopyrimidines ([18F]1 and [18F]2) were synthesized automatically at radiochemical yields 8-10% (non-decay-corrected) with molar activities of 0.95 and 0.5 GBq/µmol, respectively. The measured Kd of 6.90 nM for 1 and 14.27 nM for 2 demonstrated high affinities for LRRK2. The LRRK2 G2019S mice had higher uptakes (P < 0.01) of [18F]1 in the olfactory bulb, striatum, and hippocampus than WT mice during microPET/CT imaging, consistent with immunohistology results of LRRK2 distribution. [11C]CFT microPET/CT imaging demonstrated a lower expression of dopamine transporter in LRRK2 G2019S mice. Parkinson's disease-like deficits in dopamine transporter synthesis and cognitive declines were noticed along with LRRK2 expression increase in the olfactory bulb, striatum, and hippocampus. Therefore, 18F-labelled pyrrolopyrimidines can reflect real-time LRRK2 expression changes implicated in Parkinson's disease, which paves the way for LRRK2-related neurodegenerative precise therapy.


Assuntos
Encéfalo/metabolismo , Serina-Treonina Proteína Quinase-2 com Repetições Ricas em Leucina/genética , Sondas Moleculares/química , Doença de Parkinson/metabolismo , Pirimidinas/química , Pirróis/química , Animais , Encéfalo/patologia , Relação Dose-Resposta a Droga , Radioisótopos de Flúor , Células HEK293 , Humanos , Serina-Treonina Proteína Quinase-2 com Repetições Ricas em Leucina/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos ICR , Simulação de Acoplamento Molecular , Sondas Moleculares/síntese química , Estrutura Molecular , Doença de Parkinson/patologia , Tomografia por Emissão de Pósitrons , Pirimidinas/síntese química , Pirróis/síntese química , Relação Estrutura-Atividade
12.
Clin Nucl Med ; 46(1): 43-44, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33156044

RESUMO

Metastatic involvement of the thyroid cartilage is rare due to the absence of vessels within the cartilaginous tissue. We present the case of a 65-year-old woman recently diagnosed with breast cancer referred for skeletal staging with F-NaF PET/CT. She was found to have multiple osteoblastic metastases along with thyroid cartilage metastasis. Rare thyroid cartilage metastasis on F-NaF PET/CT may have prognostic significance in cancer patients.


Assuntos
Neoplasias da Mama/patologia , Radioisótopos de Flúor , Neoplasias Laríngeas/diagnóstico por imagem , Neoplasias Laríngeas/secundário , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Fluoreto de Sódio , Cartilagem Tireóidea/diagnóstico por imagem , Idoso , Neoplasias Ósseas/secundário , Feminino , Humanos , Prognóstico
13.
Clin Nucl Med ; 46(1): e65-e67, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33181733

RESUMO

A 46-year-old man with end-stage renal disease and renal cell carcinoma underwent F-FDG PET/CT for initial staging followed by F-PSMA-1007 PET/CT. Unlike F-FDG, which undergoes renal clearance, F-PSMA-1007 undergoes hepatobiliary clearance and thus generates superior quality images. F-PSMA-1007 PET/CT showed intense tracer-avid left renal mass lesion (FDG nonavid); lytic bone lesions (FDG avid) and single liver lesion (FDG nonavid). This case highlights the superiority of F-PSMA-1007 over F-FDG PET/CT in identifying primary lesion as well as metastatic sites in case of renal cell carcinoma even in the presence of end-stage renal disease.


Assuntos
Carcinoma de Células Renais/diagnóstico por imagem , Carcinoma de Células Renais/patologia , Falência Renal Crônica/complicações , Neoplasias Renais/diagnóstico por imagem , Neoplasias Renais/patologia , Niacinamida/análogos & derivados , Oligopeptídeos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Carcinoma de Células Renais/complicações , Feminino , Radioisótopos de Flúor , Humanos , Neoplasias Renais/complicações , Pessoa de Meia-Idade , Estadiamento de Neoplasias
14.
Clin Nucl Med ; 46(5): e273-e275, 2021 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-33323739

RESUMO

ABSTRACT: A 68-year-old man underwent 18F-prostate-specific membrane antigen (PSMA) PET/CT for staging of a newly diagnosed prostate adenocarcinoma. Unexpectedly, PET/CT revealed high focal 18F-PSMA brain uptake, which initially was suspected for a brain metastasis. Corresponding CT and MRI scans revealed characteristic imaging features of an intracranial dermoid cyst at this site. This is an exceptional location for a dermoid cyst, which had been followed up conservatively with no substantial changes. This case shows that dermoid cyst should be added to the reported list of benign neoplasms that shows "false-positive" PSMA uptake during evaluation of patients with prostate carcinoma, representing a potential interpretative pitfall.


Assuntos
Antígenos de Superfície/metabolismo , Cisto Dermoide/diagnóstico por imagem , Radioisótopos de Flúor , Glutamato Carboxipeptidase II/metabolismo , Achados Incidentais , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Neoplasias da Próstata/complicações , Idoso , Transporte Biológico , Cisto Dermoide/complicações , Cisto Dermoide/metabolismo , Humanos , Masculino , Estadiamento de Neoplasias , Neoplasias da Próstata/patologia
16.
Clin Nucl Med ; 46(5): e250-e252, 2021 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-33323731

RESUMO

ABSTRACT: 18F-prostate-specific membrane antigen (PSMA) PET/CT imaging is increasingly used in staging, assessment of biochemical recurrence, and treatment response in men with prostate cancer. We present a case report of a 70-year-old man who underwent 18F-PSMA PET/CT imaging to investigate biochemical recurrence following radical prostatectomy for prostate adenocarcinoma. New focal moderate PSMA uptake was identified in the left femur. A previous PSMA study, performed 5 months earlier, was normal. A subsequent MRI scan demonstrated that the PSMA avidity corresponded to a new femoral bone infarct. An English literature search revealed no previous cases of PSMA tracer uptake in bone infarction.


Assuntos
Antígenos de Superfície/metabolismo , Neoplasias Ósseas/diagnóstico por imagem , Neoplasias Ósseas/secundário , Radioisótopos de Flúor , Glutamato Carboxipeptidase II/metabolismo , Infarto/diagnóstico por imagem , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Neoplasias da Próstata/patologia , Idoso , Neoplasias Ósseas/metabolismo , Osso e Ossos/diagnóstico por imagem , Osso e Ossos/patologia , Diagnóstico Diferencial , Humanos , Imageamento por Ressonância Magnética , Masculino , Prostatectomia , Neoplasias da Próstata/cirurgia
17.
Eur J Nucl Med Mol Imaging ; 48(5): 1312-1326, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33340054

RESUMO

BACKGROUND: Many malignant tumours have increased TSPO expression, which has been related to a poor prognosis. TSPO-PET tracers have not comprehensively been evaluated in peripherally located tumours. This study aimed to evaluate whether N,N-diethyl-2-(2-(4-([18F]fluoro)phenyl)-5,7-dimethylpyrazolo[1,5-a]pyrimidin-3-yl)acetamide ([18F]F-DPA) can reflect radiotherapy (RT)-induced changes in TSPO activity in head and neck squamous cell carcinoma (HNSCC). METHODS: RT was used to induce inflammatory responses in HNSCC xenografts and cells. [18F]F-DPA uptake was measured in vivo in non-irradiated and irradiated tumours, followed by ex vivo biodistribution, autoradiography, and radiometabolite analysis. In vitro studies were performed in parental and TSPO-silenced (TSPO siRNA) cells. TSPO protein and mRNA expression, as well as tumour-associated macrophages (TAMs), were also assessed. RESULTS: In vivo imaging and ex vivo measurement revealed significantly higher [18F]F-DPA uptake in irradiated, compared to non-irradiated tumours. In vitro labelling studies with cells confirmed this finding, whereas no effect of RT on [18F]F-DPA uptake was detected in TSPO siRNA cells. Radiometabolite analysis showed that the amount of unchanged [18F]F-DPA in tumours was 95%, also after irradiation. PK11195 pre-treatment reduced the tumour-to-blood ratio of [18F]F-DPA by 73% in xenografts and by 88% in cells. TSPO protein and mRNA levels increased after RT, but were highly variable. The proportion of M1/M2 TAMs decreased after RT, whereas the proportion of monocytes and migratory monocytes/macrophages increased. CONCLUSIONS: [18F]F-DPA can detect changes in TSPO expression levels after RT in HNSCC, which does not seem to reflect inflammation. Further studies are however needed to clarify the physiological mechanisms regulated by TSPO after RT.


Assuntos
Radioisótopos de Flúor , Neoplasias de Cabeça e Pescoço , Animais , Neoplasias de Cabeça e Pescoço/diagnóstico por imagem , Neoplasias de Cabeça e Pescoço/radioterapia , Tomografia por Emissão de Pósitrons , Pirazóis , Pirimidinas , Distribuição Tecidual
18.
Molecules ; 25(24)2020 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-33371284

RESUMO

Recent progress realized in the development of optical imaging (OPI) probes and devices has made this technique more and more affordable for imaging studies and fluorescence-guided surgery procedures. However, this imaging modality still suffers from a low depth of penetration, thus limiting its use to shallow tissues or endoscopy-based procedures. In contrast, positron emission tomography (PET) presents a high depth of penetration and the resulting signal is less attenuated, allowing for imaging in-depth tissues. Thus, association of these imaging techniques has the potential to push back the limits of each single modality. Recently, several research groups have been involved in the development of radiolabeled fluorophores with the aim of affording dual-mode PET/OPI probes used in preclinical imaging studies of diverse pathological conditions such as cancer, Alzheimer's disease, or cardiovascular diseases. Among all the available PET-active radionuclides, 18F stands out as the most widely used for clinical imaging thanks to its advantageous characteristics (t1/2 = 109.77 min; 97% ß+ emitter). This review focuses on the recent efforts in the synthesis and radiofluorination of fluorescent scaffolds such as 4,4-difluoro-4-bora-diazaindacenes (BODIPYs), cyanines, and xanthene derivatives and their use in preclinical imaging studies using both PET and OPI technologies.


Assuntos
Corantes Fluorescentes/administração & dosagem , Radioisótopos de Flúor/administração & dosagem , Imagem Molecular/métodos , Imagem Óptica/métodos , Animais , Doença , Fluorescência , Humanos , Neoplasias/diagnóstico , Tomografia por Emissão de Pósitrons/métodos , Compostos Radiofarmacêuticos/administração & dosagem
19.
Biomedica ; 40(Supl. 2): 27-33, 2020 10 30.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-33152185

RESUMO

COVID-19 is the viral infection caused by SARS-CoV-2 declared by the World Health Organization (WHO) as a pandemic. Patients with cancer have a higher risk to acquire the infection and worse prognosis as they have to attend more medical visits in healthcare institutions, receive medical and surgical treatments, and be subjected to diagnostic studies such as PET/CT in nuclear medicine services where the infection may be an incidental finding. We present here F18-FDG PET/CT (Positron Emission Tomography and Computed Tomography with 2-deoxy-2-[fluorine-18]fluoro-D-glucose), images with findings of COVID-19 from patients with different oncological conditions but no respiratory symptoms.


Assuntos
Betacoronavirus/isolamento & purificação , Infecções por Coronavirus/diagnóstico por imagem , Achados Incidentais , Neoplasias/complicações , Pneumonia Viral/diagnóstico por imagem , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Adulto , Idoso , Doenças Assintomáticas , Carcinoma de Células em Anel de Sinete/complicações , Carcinoma de Células em Anel de Sinete/diagnóstico por imagem , Carcinoma de Células em Anel de Sinete/secundário , Técnicas de Laboratório Clínico , Infecções por Coronavirus/complicações , Infecções por Coronavirus/diagnóstico , Feminino , Radioisótopos de Flúor , Fluordesoxiglucose F18 , Humanos , Metástase Linfática/diagnóstico por imagem , Linfoma não Hodgkin/complicações , Linfoma não Hodgkin/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Neoplasias/diagnóstico por imagem , Pandemias , Derrame Pleural/diagnóstico por imagem , Derrame Pleural/etiologia , Pneumonia Viral/complicações , Compostos Radiofarmacêuticos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Seminoma/complicações , Seminoma/diagnóstico por imagem , Seminoma/secundário , Neoplasias Gástricas
20.
Medicine (Baltimore) ; 99(41): e22486, 2020 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-33031282

RESUMO

RATIONALE: Prostate-specific membrane antigen positron emission tomography-computed tomography (F-PSMA-1007 PET/CT) imaging is an emerging method for the diagnosis of prostate cancer (PC), but its efficiency in detecting other accompanying diseases has rarely been investigated. PATIENT CONCERNS: A 77-year-old man presented with a complaint of bone pain throughout his entire body lasting for 2 weeks. Routine preoperative whole-body bone scanning revealed multiple osteogenic metastases. His alpha-fetoprotein and prostate-specific antigen levels were 108.2 ng/mL and 53.32 ng/mL, respectively. F-PSMA-1007 PET/CT imaging revealed high tracer uptake in the primary lesion in the liver and the peripheral zone of the prostate. DIAGNOSES: Due to the results from imaging and pathological examinations, a diagnosis of PC with multiple bone metastases accompanied by primary hepatocellular carcinoma was made. INTERVENTIONS: Taking into consideration the patient's age, interventional therapy was performed for the liver lesion, whereas the prostate and bone lesions were treated with endocrine therapy. OUTCOMES: The patient recovered well and was discharged uneventfully postoperatively. The patient was also doing well at the 6-month follow-up. LESSONS: PSMA-PET/CT imaging results must be interpreted cautiously when the uptake of PSMA increases in a single lesion instead of the most common sites of PC metastasis. Pathological examination of the suspected lesions is also recommended.


Assuntos
Carcinoma Hepatocelular/diagnóstico por imagem , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Primárias Múltiplas/diagnóstico por imagem , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Idoso , Antígenos de Superfície , Radioisótopos de Flúor , Glutamato Carboxipeptidase II , Humanos , Achados Incidentais , Masculino , Neoplasias da Próstata
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