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1.
Medicine (Baltimore) ; 99(16): e19620, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32311931

RESUMO

For the diagnosis of mild cognitive impairment (MCI) and Alzheimer disease (AD), variable neuroimaging and neuropsychological tests have been used. We aimed to evaluate the correlation of neuropsychological domain with new amyloid positron emission tomography (PET) study and to validate the availability of new PET tracer.We enrolled 20 patients who underwent C-PiB-PET/CT, new PET tracer F-FC119S PET/CT from November, 2014 to July, 2015. Among them, 10 patients were diagnosed with AD and 10 patients with MCI. The current version of Seoul Neuropsychological Screening Battery (SNSB) II was performed for cognitive evaluation. Each parameter of SNSB was compared between 2 patient groups. Spearman correlation analysis between value of SNSB domain and standardized uptake value ratio (SUVR) of PET was also performed.The AD group presented significant poor z-score in Korean-Boston Naming Test(K-BNT) (P = .01),copy score of Rey Complex Figure Test (RCFT) (P = .049), immediate (P = .028)and delayed memory of Seoul Verbal Learning Test (SVLT) (P = .028), recognition of RCFT (P = .004), "animal" of Controlled Oral Word Association Test (COWAT) (P = .041), color reading of Korean-Color Word Stroop test (K-CWST) (P = .014), and Digit Symbol Coding (DSC) (P = .007) compared with MCI group. That means, except attention domain, all other cognitive domains were relatively impaired in AD compared with MCI. In correlation analysis, we found that poor performances on copy score of RCFT in MCI groups were associated with great beta amyloid burden in frontal area in both C-PiB-PET/CT and F-FC119S PET/CT. In AD group, F-FC119S PET presented more extensive correlation in each cognitive domain with multiple cortical areas compared with C-PiB-PET.The degree of amyloid burden assessed on F-FC119S PET was significantly correlated with neuropsychological test in AD, and also MCI patients. The combination of neuropsychological evaluation with novel F-FC119S PET/CT can be used for valid biomarker for MCI and AD.


Assuntos
Doença de Alzheimer/diagnóstico por imagem , Amiloide/metabolismo , Disfunção Cognitiva/diagnóstico por imagem , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons/métodos , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/metabolismo , Doença de Alzheimer/psicologia , Compostos de Anilina , Radioisótopos de Carbono , Disfunção Cognitiva/metabolismo , Disfunção Cognitiva/psicologia , Feminino , Radioisótopos de Flúor , Humanos , Masculino , Pessoa de Meia-Idade , Neuroimagem/métodos , Testes Neuropsicológicos , Traçadores Radioativos , Tiazóis
2.
Medicine (Baltimore) ; 99(14): e19662, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32243399

RESUMO

The value of dual imaging mode for the severity assessment of Parkinson disease (PD) is explored by conducting positron emission tomography computed tomography (PET/CT) double imaging using combined 18-fluorine flurodeoxyglucose (F-FDG) brain metabolism and 11C-2ß-carbomethoxy-3ß-(4-fluorophenyl) tropane (C-CFT) brain dopamine transporter (DAT).A total of 102 patients with PD and 50 healthy people in the control group are enrolled for the PET/CT dual imaging of F-FDG brain metabolism and C-CFT brain DAT. The characteristics of F-FDG PET/CT and C-CFT PET/CT imaging are analyzed by delineating the region of interest. Differences in the glucose metabolism and DAT distribution in the basal ganglia of patients with PD and healthy control group in the PET/CT imaging and the radioactive distribution characteristics of cerebral cortex in glucose metabolism imaging are compared. The characteristics of PET/CT imaging of C-CFT brain DAT in the ganglion region in absorbing C-CFT in different PD groups are analyzed.Compared with the healthy control group, changes in the cerebral glucose metabolism in the PD group mainly occur due to the increased symmetry metabolism of the nucleus of bilateral basal ganglia and the decreased metabolism of the cerebral cortex as shown in the F-FDG PET/CT images. With disease progression, the bilateral parietal, frontal, temporal, and occipital leaves showed different degrees of FDG metabolism. Statistically significant difference is observed for theC-CFT absorption among the caudate nucleus and the anterior, middle, and posterior nuclei of the bilateral basal ganglia of the PD and healthy control groups. In the PD group, the bilateral caudate nucleus and the anterior, middle, and posterior parts of the putamen show decreased DAT distribution. Regardless of unilateral or bilateral symptoms, the DAT distribution in the nucleus of the contralateral basal ganglia and in the posterior part of the nucleus is substantially reduced.PET/CT dual imaging by F-FDG PET/CT combined with C-CFT PET/CT features high application value for the severity assessment of PD.


Assuntos
Radioisótopos de Carbono , Cocaína/análogos & derivados , Radioisótopos de Flúor , Doença de Parkinson/diagnóstico por imagem , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons/métodos , Idoso , Gânglios da Base/diagnóstico por imagem , Gânglios da Base/metabolismo , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Feminino , Glucose/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/metabolismo , Estudos Prospectivos , Índice de Gravidade de Doença
3.
Nat Protoc ; 15(4): 1525-1541, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32111986

RESUMO

Positron emission tomography (PET) is a diagnostic nuclear imaging modality that relies on automated protocols to prepare agents labeled with a positron-emitting radionuclide (e.g., 18F). In recent years, new reactions have appeared for the 18F-labeling of agents that are difficult to access by applying traditional radiochemistry, for example those requiring 18F incorporation into unactivated (hetero)arenes. However, automation of these new methods for translation to the clinic has progressed slowly because extensive modification of manual protocols is typically required when implementing novel 18F-labeling methodologies within automated modules. Here, we describe the workflow that led to the automated radiosynthesis of the poly(ADP-ribose) polymerase (PARP) inhibitor [18F]olaparib. First, we established a robust manual protocol to prepare [18F]olaparib from the protected N-[2-(trimethylsilyl)ethoxy]methyl (SEM) arylboronate ester precursor in a 17% ± 5% (n = 15; synthesis time, 135 min) non-decay-corrected (NDC) activity yield, with molar activity (Am) up to 34.6 GBq/µmol. Automation of the process, consisting of copper-mediated 18F-fluorodeboronation followed by deprotection, was achieved on an Eckert & Ziegler Modular-Lab radiosynthesis platform, affording [18F]olaparib in a 6% ± 5% (n = 3; synthesis time, 120 min) NDC activity yield with Am up to 319 GBq/µmol.


Assuntos
Técnicas de Química Sintética/métodos , Cobre/química , Radioisótopos de Flúor/química , Ftalazinas , Piperazinas , Inibidores de Poli(ADP-Ribose) Polimerases , Automação , Ftalazinas/síntese química , Ftalazinas/química , Piperazinas/síntese química , Piperazinas/química , Inibidores de Poli(ADP-Ribose) Polimerases/síntese química , Inibidores de Poli(ADP-Ribose) Polimerases/química , Tomografia por Emissão de Pósitrons , Radioquímica , Compostos Radiofarmacêuticos/síntese química , Compostos Radiofarmacêuticos/química
4.
Chem Commun (Camb) ; 56(16): 2507-2510, 2020 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-32003763

RESUMO

Radiolabeling of peptides with fluorine-18 is hurdled by their chemical sensitivity and complicated processes. Original triflyl-pyridine intermediates afforded ammonium precursors that were radiolabeled at low temperature. From that study, a generic tag has been designed to allow a simple one-step/late-stage radiolabelling of peptides. The strategy has been transposed to an automated "on-resin" radiolabelling.


Assuntos
Peptídeos/síntese química , Compostos Radiofarmacêuticos/síntese química , Resinas Sintéticas/síntese química , Radioisótopos de Flúor , Halogenação , Estrutura Molecular , Peptídeos/química , Compostos Radiofarmacêuticos/química , Resinas Sintéticas/química , Temperatura
5.
Medicine (Baltimore) ; 99(2): e18681, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31914064

RESUMO

Hyperparathyroidism is a common endocrine disorder. The precise localization of causal parathyroid gland is crucial to guide surgical treatment. Several studies report the added value of 18F-fluorocholine (FCH) positron emission tomography-computed tomography (PET/CT) as second line imaging but rely on suboptimal first-line imaging using 99mTc-sestaMIBI dual phase scintigraphy. The aim of this study is to evaluate the percentage of successful parathyroid localization with FCH PET/CT after failure of a more sensitive first-line detection protocol associating neck ultrasonography and 99mTc-Pertechnetate/99mTc-sestaMIBI dual tracer subtraction scintigraphy.We included retrospectively 47 patients who underwent a FCH PET/CT as second line imaging for biologically proven primary hyperparathyroidism from November 2016 to October 2018 in Godinot Institute (Reims, France). 99mTc-Pertechnetate/99mTc-sestaMIBI dual tracer subtraction scintigraphy and neck ultrasonography were used as first-line imaging and failed to localize the causal parathyroid lesion in all cases.FCH PET/CT demonstrated at least 1 parathyroid target lesion in 29 patients (62%). 21/29 patients underwent surgery. Target lesions corresponded histologically to hyperfunctioning parathyroid glands for all 21 patients and surgery was followed by hyperparathyroidism biological resolution. Calcium serum levels were associated to FCH PET/CT positivity (P = .002) and a trend toward significance was seen for Parathyroid hormone (PTH) levels (P = .09).FCH PET/CT is a promising tool in second-line parathyroid imaging. Large prospective studies and cost-effectiveness analyses are needed to precise its role.


Assuntos
Colina/análogos & derivados , Radioisótopos de Flúor/administração & dosagem , Hiperparatireoidismo/diagnóstico por imagem , Glândulas Paratireoides/diagnóstico por imagem , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons/métodos , Idoso , Idoso de 80 Anos ou mais , Colina/administração & dosagem , Feminino , Humanos , Hiperparatireoidismo/patologia , Masculino , Pessoa de Meia-Idade , Glândulas Paratireoides/patologia , Cintilografia/métodos , Estudos Retrospectivos , Tecnécio Tc 99m Sestamibi/administração & dosagem
6.
Yakugaku Zasshi ; 140(1): 7-13, 2020.
Artigo em Japonês | MEDLINE | ID: mdl-31902888

RESUMO

Matrix metalloproteinases (MMPs) regulate various cellular functions, such as motility, invasion, differentiation, and apoptosis. Precise in vivo quantification of MMPs in disease can provide beneficial information for both basic and clinical research studies. To this end, various types of probes have been developed for imaging MMPs in vivo. In this review, representative MMP-targeted probes, such as binding probes and activatable probes, are outlined, including highlights of our own research. In addition, strategies for the development of probes that apply "theranostics," a concept that integrates therapy and diagnostics, are elucidated with reference to [18F]IPFP, a new probe developed in our laboratory. [18F]IPFP was prepared by iodination of a known MMP inhibitor to enhance its affinity and labeled with the compact prosthetic agent 4-nitrophenyl 2-[18F]fluoropropionate ([18F]NFP) for MMP-targeted positron-emission tomography (PET) and other therapeutic properties. IPFP demonstrated high inhibitory activity toward MMP-12 (IC50 value=1.5 nM). Radioactivity accumulation in the lungs 90 min after administration of [18F]IPFP was 4-fold higher in chronic obstructive pulmonary disease (COPD) mice overexpressing MMPs compared with normal mice. Ex vivo PET confirmed the radioactivity distribution in tissues, and autoradiography analysis demonstrated accumulation differences between COPD and normal mice. Consequently, [18F]IPFP showed potent inhibitory activities against MMPs and suitable pharmacokinetics for imaging pulmonary disease. Thus, [18F]IPFP is a promising theranostic probe for pulmonary disease and is expected to be applied to various other MMP-related diseases. Strategies for MMP probe development introduced in this review are anticipated to lead to the development of superior imaging probes in the future.


Assuntos
Corantes Fluorescentes , Metaloproteinases da Matriz/análise , Imagem Molecular/métodos , Animais , Biomarcadores/análise , Radioisótopos de Flúor , Humanos , Metaloproteinases da Matriz/fisiologia , Camundongos , Tomografia por Emissão de Pósitrons , Doença Pulmonar Obstrutiva Crônica , Compostos Radiofarmacêuticos , Nanomedicina Teranóstica , Tomografia Computadorizada de Emissão de Fóton Único
7.
Int J Radiat Oncol Biol Phys ; 106(3): 546-555, 2020 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-31730876

RESUMO

PURPOSE: Radio-recurrent prostate cancer is typically detected by a rising prostate-specific antigen and may reflect local or distant disease. Positron emission tomography (PET) radiotracers targeting prostate-specific membrane antigen, such as 18F-DCFPyL have shown promise in restaging men with recurrent disease postprostatectomy but are less well characterized in the setting of radio-recurrent disease. METHODS AND MATERIALS: A prospective, multi-institutional study was conducted to evaluate the effect of 18F-DCFPyL PET/computed tomography (CT) when added to diagnostic imaging (DI; CT abdomen and pelvis, bone scan, multiparametric magnetic resonance imaging pelvis) for men with radio-recurrent prostate cancer. All men were imaged with DI and subsequently underwent 18F-DCFPyL PET/CT with local and central reads. Tie break reads were performed as required. Management questionnaires were completed after DI and again after 18F-DCFPyL PET/CT. Discordance in patterns of disease detected with 18F-DCFPyL PET/CT versus DI and changes in management were characterized. RESULTS: Seventy-nine men completed the study. Most men had T1 disease (62%) and Gleason score <7 (95%). Median prostate-specific antigen at diagnosis was 7.4 ng/mL and at relapse was 4.8 ng/mL. DI detected isolated intraprostatic recurrence in 38 out of 79 men (48%), regional nodal recurrence in 9 out of 79 (11%), distant disease in 12 out of 79 (15%), and no disease in 26 out of 79 (33%). 18F-DCFPyL PET/CT detected isolated intraprostatic recurrence in 38 out of 79 men (48%), regional nodal recurrence in 21 out of 79 (27%), distant disease in 24 out of 79 (30%), and no disease in 10 out of 79 (13%). DI identified 8 out of 79 (10%) patients to have oligometastatic disease, compared with 21 out of 79 (27%) with 18F-DCFPyL PET/CT. 18F-DCFPyL PET/CT changed proposed management in 34 out of 79 (43%) patients. CONCLUSIONS: 18F-DCFPyL PET/CT identified extraprostatic disease in twice as many men with radio-recurrent prostate cancer compared with DI and detected a site of recurrence in 87% of men compared with 67% with DI. Furthermore, 18F-DCFPyL PET/CT identified potentially actionable disease (prostate only recurrence or oligometastatic disease) in 75% of men and changed proposed management in 43% of men.


Assuntos
Lisina/análogos & derivados , Recidiva Local de Neoplasia/diagnóstico por imagem , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons/métodos , Neoplasias da Próstata/diagnóstico por imagem , Ureia/análogos & derivados , Idoso , Idoso de 80 Anos ou mais , Antígenos de Superfície/sangue , Radioisótopos de Flúor , Glutamato Carboxipeptidase II/sangue , Humanos , Calicreínas/sangue , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/sangue , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/radioterapia , Estudos Prospectivos , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/sangue , Neoplasias da Próstata/patologia , Neoplasias da Próstata/radioterapia
8.
Eur J Med Chem ; 187: 111979, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31877537

RESUMO

Fluorine-18 is one of the most widely used radionuclides for the production of radiopharmaceuticals for positron emission tomography (PET). The radiolabeling methods like nucleophilic, electrophilic, Cu mediated mechanisms or prosthetic groups are widely using to achieve high regioselective radiochemical yields. It acts as a powerful tool to identify new drug targets through cellular uptake, pharmacokinetic (ADME) and pharmacodynamic parameters of the 18F labeled tracer or drug. These PET tracers have been developed based on the receptors expressed in a disease condition. A number of 18F radiotracers have been developed against the Tropomyosin Receptor Kinases (Trks), Carbonic anhydrases (CAs), Epidermal Growth Factor Receptors (EGFR), Poly ADP ribose polymerase (PARP) etc. for the diagnosis in cancer therapy. The current research also focused on the development of novel 18F radiotracers for neurological conditions for deciphering underlying physiology in diseases like Alzheimer, and Parkinson. Therefore, in this review we have focused on 18F labeling methods, and radiotracers developed against common cancers and neurological conditions.


Assuntos
Inibidores Enzimáticos/química , Neoplasias/diagnóstico por imagem , Doenças do Sistema Nervoso/diagnóstico por imagem , Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos/química , Animais , Anidrases Carbônicas/metabolismo , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/farmacologia , Receptores ErbB/antagonistas & inibidores , Receptores ErbB/metabolismo , Radioisótopos de Flúor , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Doenças do Sistema Nervoso/tratamento farmacológico , Doenças do Sistema Nervoso/metabolismo , Poli(ADP-Ribose) Polimerases/metabolismo , Compostos Radiofarmacêuticos/síntese química , Compostos Radiofarmacêuticos/farmacologia , Receptores Proteína Tirosina Quinases/antagonistas & inibidores , Receptores Proteína Tirosina Quinases/metabolismo
9.
Clin Nucl Med ; 45(1): e61-e62, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31162269

RESUMO

A 64-year-old man with a known case of right parietal lobe glioblastoma multiforme operated on in August 2018 was referred for F-FDG PET/CT with a clinical suspicion of recurrence. He underwent F-FDG and F-PSMA 1007 scans. Both the scans showed intense tracer uptake in right parietal lobe lesion, which concurred with MRI findings of recurrent disease and was later proven on histopathologic examination as recurrence. Our case highlights the feasibility of F-PSMA 1007 PET/CT imaging of suspected glioblastoma recurrence. Considering its similarity to PSMA-617, it may be used as a surrogate imaging tracer for potential theranostic application using alpha or beta emitters.


Assuntos
Neoplasias Encefálicas/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Radioisótopos de Flúor , Glioblastoma/diagnóstico por imagem , Niacinamida/análogos & derivados , Oligopeptídeos , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Encéfalo/patologia , Neoplasias Encefálicas/patologia , Glioblastoma/patologia , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Recidiva
10.
Clin Nucl Med ; 45(1): e59-e60, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31283607

RESUMO

Ocular prosthesis is used as a replacement in the orbit following enucleation or evisceration of the eye. Polymethyl methacrylate (PMMA), hydroxyapatite (HA) and porous polyethylene (PP) are some examples of the materials used in ocular prosthesis. We present a case of an 82-year-old man with prostate cancer who underwent F-NaF PET/CT imaging for evaluation of bone metastases and was incidentally found to have increased NaF uptake in the ocular prosthesis.


Assuntos
Olho Artificial , Radioisótopos de Flúor , Fluoreto de Sódio/metabolismo , Idoso de 80 Anos ou mais , Transporte Biológico , Reações Falso-Positivas , Humanos , Masculino , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia
11.
Chem Commun (Camb) ; 56(5): 723-726, 2020 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-31840690

RESUMO

A new prosthetic group is reported for 18F-labelling of peptides and proteins based on the chemoselective ligation of potassium acyltrifluoroborates (KATs) and hydroxylamines without any detectable 18F/19F isotope exchange at the acyltrifluoroborate moiety. The new building block is appended via a common amide bond at room temperature with no need for protecting groups which enables an effective orthogonal 18F-radiolabelling.


Assuntos
Boratos/química , Radioisótopos de Flúor/química , Marcação por Isótopo/métodos , Peptídeos/química , Proteínas/química , Piridinas/química , Animais , Indicadores e Reagentes/química , Masculino , Camundongos Endogâmicos C57BL , Peptídeos/metabolismo , Tomografia por Emissão de Pósitrons/métodos , Proteínas/metabolismo , Compostos Radiofarmacêuticos/química , Temperatura
12.
Clin Nucl Med ; 45(3): 223-224, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31876816

RESUMO

We report the case of a 74-year-old man with suspected recurrent prostate carcinoma who underwent F-PSMA-1007 PET/CT for restaging the disease. PET/CT imaging presented an incidentaloma with intense F-PSMA-1007 uptake in the right thyroid lobe. Biopsy and genomic sequencing test confirmed the diagnosis of Hürthle cell thyroid adenoma. Therefore, it is important to raise awareness of this benign lesion in the differential diagnosis of incidental thyroid nodules with high F-PSMA-1007 activity.


Assuntos
Adenoma Oxífilo/diagnóstico por imagem , Adenoma Oxífilo/metabolismo , Radioisótopos de Flúor , Niacinamida/análogos & derivados , Oligopeptídeos/metabolismo , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Neoplasias da Glândula Tireoide/metabolismo , Adenoma Oxífilo/complicações , Idoso , Transporte Biológico , Humanos , Masculino , Estadiamento de Neoplasias , Niacinamida/metabolismo , Neoplasias da Próstata/complicações , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/patologia , Neoplasias da Glândula Tireoide/complicações
13.
Clin Nucl Med ; 44(12): 991-992, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31689283

RESUMO

A 48-year-old woman with intermittent lower back pain for 9 months and known retroperitoneal neurofibroma underwent F-NaF PET/CT scan to assess possible bony lesions causing the pain. Incidentally, the images showed elevated NaF activity in the retroperitoneal neurofibroma. In addition, uterine leiomyoma with heterogeneous calcifications revealed increased NaF activity.


Assuntos
Calcinose/complicações , Radioisótopos de Flúor , Leiomioma/complicações , Neurofibroma/metabolismo , Neoplasias Retroperitoneais/metabolismo , Fluoreto de Sódio/metabolismo , Transporte Biológico , Humanos , Masculino , Pessoa de Meia-Idade , Neurofibroma/complicações , Neurofibroma/diagnóstico por imagem , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Neoplasias Retroperitoneais/complicações , Neoplasias Retroperitoneais/diagnóstico por imagem
14.
Nat Commun ; 10(1): 4627, 2019 10 11.
Artigo em Inglês | MEDLINE | ID: mdl-31604917

RESUMO

Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) are a popular chemogenetic technology for manipulation of neuronal activity in uninstrumented awake animals with potential for human applications as well. The prototypical DREADD agonist clozapine N-oxide (CNO) lacks brain entry and converts to clozapine, making it difficult to apply in basic and translational applications. Here we report the development of two novel DREADD agonists, JHU37152 and JHU37160, and the first dedicated 18F positron emission tomography (PET) DREADD radiotracer, [18F]JHU37107. We show that JHU37152 and JHU37160 exhibit high in vivo DREADD potency. [18F]JHU37107 combined with PET allows for DREADD detection in locally-targeted neurons, and at their long-range projections, enabling noninvasive and longitudinal neuronal projection mapping.


Assuntos
Drogas Desenhadas , Radioisótopos de Flúor/análise , Marcadores do Trato Nervoso/análise , Animais , Encéfalo , Clozapina/análogos & derivados , Clozapina/química , Células HEK293 , Haplorrinos , Humanos , Ligantes , Técnicas de Rastreamento Neuroanatômico/métodos , Marcadores do Trato Nervoso/química , Tomografia por Emissão de Pósitrons/métodos , Roedores
15.
Chem Commun (Camb) ; 55(83): 12455-12458, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31565704

RESUMO

Hypochlorous acid (HClO) is one of the most important reactive oxygen species (ROS) and plays a vital role in many physiological and pathological processes. The comprehensive exploration of mechanistic details and the potential clinical translation necessitate the development of reliable probes for prompt and accurate detection of HClO in complex biological environments. Herein we report a fluorinated bihydrazide conjugate as a 19F NMR/MRI probe with a "turn-on" character for the detection of HClO. This probe could selectively respond to HClO, leading to a significant recovery of 19F signals for 19F NMR/MRI. Activatable sensing and imaging of HClO were achieved with SMMC-7721 cells and nude mice, which demonstrates that this small molecular conjugate could serve as a selective probe for real-time sensing and imaging of HClO in biological systems.


Assuntos
Corantes Fluorescentes/química , Hidrazinas/química , Ácido Hipocloroso/análise , Imagem por Ressonância Magnética , Animais , Linhagem Celular Tumoral , Radioisótopos de Flúor , Halogenação , Humanos , Espectroscopia de Ressonância Magnética , Camundongos , Camundongos Nus , Espécies Reativas de Oxigênio
16.
Eur J Med Chem ; 183: 111730, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31563014

RESUMO

Designing novel 18F-labeled amino acid derivatives for targeted amino acid transporters is an attractive strategy for the development of therapeutic and diagnostic agents for cancer therapy. In this work, we have developed a novel 3-fluoropropyl analog of arginine, namely, (2S,4S)4-[18F]FPArg, [18F]1, to be used as a probe for studying arginine metabolism. Optically pure and labeled with 18F and 19F, (2S,4S)4-(3-fluoropropyl)arginine was synthesized and isolated in high radiochemical purity (>95%). In vitro uptake assays in human MCF-7 cells revealed that [18F]1 enters cells mainly via sodium-independent cationic amino acid transporters and was inhibited >62% by arginine. [18F]1 showed a high cellular uptake of 7.3 ±â€¯0.24% and 6.07 ±â€¯0.3% uptake/100 mg protein after incubation in MCF-7 and MDA-MB-231 cells for 120 min, respectively. In vivo biodistribution studies demonstrated that [18F]1 provided high tumor uptake and high tumor to muscle ratios (5:1 at the 30 and 60 min time points). In vivo PET imaging studies demonstrated tumor-specific uptake in nude mice bearing MCF-7 breast tumors with an excellent tumor-to-muscle ratio. These results suggest that [18F]1 is a promising tracer for clinical breast cancer imaging and may be used to diagnose and monitor diseases that are associated with arginine metabolism.


Assuntos
Arginina/análogos & derivados , Arginina/síntese química , Neoplasias da Mama/diagnóstico por imagem , Radioisótopos de Flúor/química , Tomografia por Emissão de Pósitrons/métodos , Compostos Radiofarmacêuticos/síntese química , Animais , Arginina/metabolismo , Linhagem Celular Tumoral , Permeabilidade da Membrana Celular , Estabilidade de Medicamentos , Feminino , Humanos , Camundongos Nus , Estrutura Molecular , Compostos Radiofarmacêuticos/metabolismo , Relação Estrutura-Atividade , Distribuição Tecidual
17.
Molecules ; 24(17)2019 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-31484375

RESUMO

In the era of personalized precision medicine, positron emission tomography (PET) and related hybrid methods like PET/CT and PET/MRI gain recognition as indispensable tools of clinical diagnostics. A broader implementation of these imaging modalities in clinical routine is closely dependent on the increased availability of established and emerging PET-tracers, which in turn could be accessible by the development of simple, reliable, and efficient radiolabeling procedures. A further requirement is a cGMP production of imaging probes in automated synthesis modules. Herein, a novel protocol for the efficient preparation of 18F-labeled aromatics via Cu-mediated radiofluorination of (aryl)(mesityl)iodonium salts without the need of evaporation steps is described. Labeled aromatics were prepared in high radiochemical yields simply by heating of iodonium [18F]fluorides with the Cu-mediator in methanolic DMF. The iodonium [18F]fluorides were prepared by direct elution of 18F- from an anion exchange resin with solutions of the corresponding precursors in MeOH/DMF. The practicality of the novel method was confirmed by the racemization-free production of radiolabeled fluorophenylalanines, including hitherto unknown 3-[18F]FPhe, in 22-69% isolated radiochemical yields as well as its direct implementation into a remote-controlled synthesis unit.


Assuntos
Radioisótopos de Flúor/análise , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons/métodos
18.
Radiat Oncol ; 14(1): 164, 2019 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-31488175

RESUMO

INTRODUCTION: In prostate cancer patients, imaging of bone metastases is enhanced through the use of sodium fluoride positron emission tomography (18F-NaF PET/CT). This imaging technique shows areas of enhanced osteoblastic activity and blood flow. In this work, 18F-NaF PET/CT was investigated for response assessment to single fraction stereotactic ablative body radiotherapy (SABR) to bone metastases in prostate cancer patients. METHODS: Patients with bone metastases in a prospective trial treated with single fraction SABR received a 18F-NaF PET/CT scan prior to and 6 months post-SABR. The SUVmax in the tumour was determined and the difference between before and after SABR determined. The change in uptake in the non-tumour bone was also measured as a function of the received SABR dose. RESULTS: Reduction in SUVmax was observed in 29 of 33 lesions 6 months after SABR (mean absolute decrease in SUVmax 17.7, 95% CI 25.8 to - 9.4, p = 0.0001). Of the three lesions with increased SUVmax post-SABR, two were from the same patient and located in the vertebral column. Both were determined to be local progression in addition to one fracture. The third lesion (in a rib) was shown to be controlled locally but suffered from a fracture at 24 months. Progression adjacent to the treated volume was observed in two patients. The non-tumour bone irradiated showed increased loss in uptake with increasing dose, with a median loss in uptake of 23.3% for bone receiving 24 Gy. CONCLUSION: 18F-NaF PET/CT for response assessment of bone metastases to single fraction SABR indicates high rates of reduction of osteoblastic activity in the tumour and non-tumour bone receiving high doses. The occurrence of marginal recurrence indicates use of larger clinical target volumes may be warranted in treatment of bone metastases. TRIAL REGISTRATION: POPSTAR, 'Pilot Study of patients with Oligometastases from Prostate cancer treated with STereotactic Ablative Radiotherapy', Universal Trial Number U1111-1140-7563 , Registered 17th April 2013.


Assuntos
Neoplasias Ósseas/secundário , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons/métodos , Neoplasias da Próstata/patologia , Radiocirurgia/métodos , Fluoreto de Sódio , Neoplasias Ósseas/diagnóstico por imagem , Neoplasias Ósseas/cirurgia , Fracionamento da Dose de Radiação , Radioisótopos de Flúor , Humanos , Masculino , Projetos Piloto , Prognóstico , Estudos Prospectivos , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/cirurgia
19.
Biomed Pharmacother ; 119: 109454, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31526971

RESUMO

OBJECTIVE: The aim of this study was to evaluate the application of 18F-flortanidazole (18F-HX4)/18F-fluoromisonidazole (18F-FMISO) - based micro positron emission tomography/computed tomography (PET/CT) for imaging of tumor hypoxia and radiotherapy-associated changes in mice. MATERIALS AND METHODS: Radiotracer-based cellular uptake was performed to explore the correlation between radiotracer uptake and hypoxia state in cells. Animal models were established using subcutaneous injection of the human breast cancer line (MDA-MB-231) in a nude mouse. The effect of radiotherapy on tumor xenograft was assessed by measuring the tumor volume and mouse survival time. Meanwhile, mice with xenograft were imaged with 18F-FMISO and18F-HX4 PET/CT before and after radiotherapy. Tumor-to-normal muscle ratio (T/N) of 18F-FMISO and18F-HX4 maximum uptake was calculated by selecting a region of interest. Changes in tumor biology were assessed with immunohistochemical staining; T/N (18F-FMISO) and T/N (18F-HX4) were analyzed in relation to tumor volume, survival time, and the expression of tumor biomarkers, including hypoxia-inducible factor (HIF)-1α, glucose transporter (Glut-1) and the proliferation antigen Ki67. RESULTS: Higher tracer uptake (both 18F-FMISO and 18F-HX4) was observed in hypoxic cells compared to oxygenated cell. The in vivo study suggested that both T/N (18F-FMISO) and T/N (18F-HX4) were positively correlated with tumor hypoxia volume (p = 0.014 and p = 0.009, respectively), but negatively associated with survival time (p = 0.012 and p = 0.007, respectively). HIF-1α, Glut-1 and Ki67 expression in tumors were downregulated after radiotherapy. T/N (18F-HX4) was correlated with the expression of hypoxia marker HIF-1α in xenografts (r = 0.768, p = 0.025); while T/N (18F-FMISO) was moderately correlated with the expressions of Ki67 (r = 0.412, p = 0.041). No significant correlation was detected between Glut-1 expression and T/N (18F-FMISO) or T/N (18F-HX4) (r = 0.511, p = 0.097 and r=0.562, p = 0.126, respectively). CONCLUSIONS: Both 18F-HX4 and 18F-FMISO PET/CT can be used as biomarkers for tumor hypoxia and radiotherapy-associated changes. The clinical utilization of these two PET tracers needs to be further validated.


Assuntos
Azóis/química , Radioisótopos de Flúor/química , Misonidazol/análogos & derivados , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Hipóxia Tumoral , Animais , Biomarcadores Tumorais/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Feminino , Humanos , Modelos Lineares , Camundongos Endogâmicos BALB C , Camundongos Nus , Misonidazol/química , Análise Multivariada , Tomografia Computadorizada por Raios X , Carga Tumoral , Ensaios Antitumorais Modelo de Xenoenxerto
20.
BMC Cancer ; 19(1): 767, 2019 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-31382920

RESUMO

BACKGROUND: Positron emission tomography (PET) and PET/computed tomography (PET/CT) imaging with 3,4-dihydroxy-6-[18F] fluoro-L-phenylalanine (18F-FDOPA) has been used in the evaluation of gliomas. We performed a meta-analysis to obtain the diagnostic and grading accuracy of 18F-FDOPA PET and PET/CT in patients with gliomas. METHODS: PubMed, Embase, Cochrane Library and Web of Science were searched through 13 May 2019. We included studies reporting the diagnostic performance of 18F-FDOPA PET or PET/CT in glioma patients. Pooled sensitivity, specificity, and area under the summary receiver operating characteristic (SROC) curve were calculated from eligible studies on a per-lesion basis. RESULTS: Eventually, 19 studies were included. Across 13 studies (370 patients) for glioma diagnosis, the pooled sensitivity and specificity of 18F-FDOPA PET and PET/CT were 0.90 (95%CI: 0.86-0.93) and 0.75 (95%CI: 0.65-0.83). Across 7 studies (219 patients) for glioma grading, 18F-FDOPA PET and PET/CT showed a pooled sensitivity of 0.88 (95%CI: 0.81-0.93) and a pooled specificity of 0.73 (95%CI: 0.64-0.81). CONCLUSIONS: 18F-FDOPA PET and PET/CT demonstrated good performance for diagnosing gliomas and differentiating high-grade gliomas (HGGs) from low-grade gliomas (LGGs). Further studies implementing standardized PET protocols and investigating the grading parameters are needed.


Assuntos
Neoplasias Encefálicas/diagnóstico por imagem , Radioisótopos de Flúor , Glioma/diagnóstico por imagem , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons/métodos , Tomografia por Emissão de Pósitrons/métodos , Adolescente , Adulto , Idoso , Criança , Confiabilidade dos Dados , Feminino , Formicinas , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Recidiva Local de Neoplasia/diagnóstico por imagem , Viés de Publicação , Curva ROC , Compostos Radiofarmacêuticos , Ribonucleotídeos , Sensibilidade e Especificidade , Adulto Jovem
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