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1.
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
2.
Curr Med Chem ; 27(4): 501-522, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31142249

RESUMO

Positron Emission Tomography (PET) and Single Photon Emission Computerized Tomography (SPECT) are ultra-sensitive, fully translational and minimally invasive nuclear imaging techniques capable of tracing the spatiotemporal distribution of positron (PET) or gamma (SPECT) emitter-labeled molecules after administration into a living organism. Besides their impact in the clinical diagnostic, PET and SPECT are playing an increasing role in the process of drug development, both during the evaluation of the pharmacokinetic properties of new chemical entities as well as in the proof of concept, proof of mechanism and proof of efficacy studies. However, they have been scarcely applied in the context of ophthalmic drugs. In this paper, the basics of nuclear imaging and radiochemistry are briefly discussed, and the few examples of the use of these imaging modalities in ophthalmic drug development reported in the literature are presented and discussed. Finally, in a purely theoretical exercise, some labeling strategies that could be applied to the preparation of selected ophthalmic drugs are proposed and potential applications of nuclear imaging in ophthalmology are projected.


Assuntos
Descoberta de Drogas , Tomografia por Emissão de Pósitrons , Radioquímica
3.
Chemosphere ; 242: 125169, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31675576

RESUMO

A systematic study on desorption of uranium in a natural soil has been carried out to reduce the level of uncertainty associated with the method employed to determine the values of the distribution coefficient (Kd). Generally, the operating method used to extract and analyze the soil solution determines the Kd values. Here, the centrifugation method has been used to obtain soil solution extracts. Several procedural parameters have been considered such as incubation time, the level of soil moisture relative to saturation (saturation degree) and centrifugation speed (equivalent to effective suction). In order to analyze the influence of soil structural characteristics, this study considers three grain-size fractions of soil: loamy coarse sand, loamy fine sand, and loam, all of which are obtained from a natural soil collected in a uranium mineralized area. Our results indicate that neither incubation time nor centrifugation speed influence the determination of Kd for uranium. The results also indicate that the level of soil moisture is the most important factor for determining 238U-Kd. It has been shown that the influence of moisture on Kd also depends on the structural characteristic of the soil. For the loamy coarse sand subsample, the moisture level during the incubation period showed a significant influence on the Kd. In addition, through the use of regression analysis, the pH was identified as the cofactor with the greatest influence on Kd of uranium.


Assuntos
Monitoramento Ambiental/métodos , Poluentes Radioativos do Solo/análise , Solo/química , Urânio/análise , Concentração de Íons de Hidrogênio , Radioquímica , Água/análise
4.
Dalton Trans ; 49(4): 1097-1106, 2020 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-31872829

RESUMO

Radiolabelled lipophilic cations could potentially be used to non-invasively image mitochondrial dysfunction in cardiovascular disease, building on their current role as perfusion imaging agents. We have synthesised and radiolabelled two series of DO2A-based radiotracers, with bistriarylphosphonium- and bisaryl-functionalisation respectively, with gallium-68 to form lipophilic cations. Both sets of tracers radiolabel with over 90% RCP, although the tracers form kinetic/thermodynamic pairs of species upon gallium chelation that can be visualised and separated by radioHPLC. Log D7.4 values above -0.3 are observed for the most lipophilic examples of each series of radiotracers. Both tracers show significant preferential uptake in healthy cardiac tissue over cardiac tissue depolarised by CCCP.


Assuntos
Radioisótopos de Gálio/química , Compostos Heterocíclicos com 1 Anel/química , Compostos Heterocíclicos com 1 Anel/metabolismo , Miocárdio/metabolismo , Animais , Transporte Biológico , Técnicas de Química Sintética , Compostos Heterocíclicos com 1 Anel/síntese química , Marcação por Isótopo , Ligantes , Masculino , Tomografia por Emissão de Pósitrons , Radioquímica , Ratos , Ratos Wistar
6.
Molecules ; 24(22)2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31731831

RESUMO

A specific radioligand for the imaging of cyclic nucleotide phosphodiesterase 2A (PDE2A) via positron emission tomography (PET) would be helpful for research on the physiology and disease-related changes in the expression of this enzyme in the brain. In this report, the radiosynthesis of a novel PDE2A radioligand and the subsequent biological evaluation were described. Our prospective compound 1-(2-chloro-5-methoxy phenyl)-8-(2-fluoropyridin-4-yl)-3- methylbenzo[e]imidazo[5,1-c][1,2,4]triazine, benzoimidazotriazine (BIT1) (IC50 PDE2A = 3.33 nM; 16-fold selectivity over PDE10A) was fluorine-18 labeled via aromatic nucleophilic substitution of the corresponding nitro precursor using the K[18F]F-K2.2.2-carbonate complex system. The new radioligand [18F]BIT1 was obtained with a high radiochemical yield (54 ± 2%, n = 3), a high radiochemical purity (≥99%), and high molar activities (155-175 GBq/µmol, n = 3). In vitro autoradiography on pig brain cryosections exhibited a heterogeneous spatial distribution of [18F]BIT1 corresponding to the known pattern of expression of PDE2A. The investigation of in vivo metabolism of [18F]BIT1 in a mouse revealed sufficient metabolic stability. PET studies in mouse exhibited a moderate brain uptake of [18F]BIT1 with a maximum standardized uptake value of ~0.7 at 5 minutes p.i. However, in vivo blocking studies revealed a non-target specific binding of [18F]BIT1. Therefore, further structural modifications are needed to improve target selectivity.


Assuntos
Encéfalo , Nucleotídeo Cíclico Fosfodiesterase do Tipo 2/metabolismo , Radioisótopos de Flúor , Neuroimagem , Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos , Animais , Encéfalo/diagnóstico por imagem , Encéfalo/enzimologia , Radioisótopos de Flúor/química , Radioisótopos de Flúor/farmacocinética , Radioisótopos de Flúor/farmacologia , Radioquímica , Compostos Radiofarmacêuticos/síntese química , Compostos Radiofarmacêuticos/química , Compostos Radiofarmacêuticos/farmacocinética , Compostos Radiofarmacêuticos/farmacologia , Suínos , Distribuição Tecidual
7.
J Labelled Comp Radiopharm ; 62(13): 885-891, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31677180

RESUMO

Labeling agents with radioisotopes or fluorescent dyes are useful for investigating the biodistributions of biologically active proteins and peptides. Compared with molecular imaging with a single modality, dual imaging probes provide complementary information for each modality. The development of a dual radioisotope/fluorescence agent for protein labeling would thus be valuable for both preclinical and clinical applications. In this study, we designed and synthesized a radioiodinated BODIPY derivative (BODIPY-ML) with a maleimide group as a thiol-labeling agent. In the presence of N-chlorosuccinimide and 1% acetic acid, [125 I]BODIPY-ML was successfully obtained at a radiochemical yield of 42%. In conjugation studies, model proteins including RGD peptides and anti-HER2 VHH were successfully labeled with BODIPY-ML via covalent bonds. The results demonstrated the feasibility of the radioiodinated BODIPY as a dual-labeling agent via thiol groups.


Assuntos
Compostos de Boro/química , Compostos de Boro/síntese química , Halogenação , Radioisótopos do Iodo/química , Compostos de Sulfidrila/química , Técnicas de Química Sintética , Marcação por Isótopo , Oligopeptídeos/química , Radioquímica
8.
Carbohydr Res ; 486: 107827, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31586720

RESUMO

Rare sugars are defined as monosaccharides that exist in nature but are only present in limited quantities. d-Allose is a rare sugar that has been reported to have some unique physiological effects. The present study describes suitable synthetic procedures for novel rare sugars of d-allose that are 18F-labeled at the C-3 and C-6 positions and the preparation of the appropriate labeling precursors. The goal is to facilitate in vivo, noninvasive positron emission tomography (PET) investigation of the behavior of rare sugar analogs of d-allose in organs. We found five precursors that were practical for labeling, three for 3-deoxy-3-[18F]fluoro-d-allose ([18F]3FDA) and two for 6-deoxy-6-[18F]fluoro-d-allose ([18F]6FDA). With manual operation synthesis, the highest radiochemical conversion rates were 75% for [18F]3FDA with a precursor of 1,2,4,6-tetra-O-acetyl-3-O-trifluoromethanesulfonyl-ß-d-glucopyranose and 69% for [18F]6FDA with a precursor of 1,2,3,4-tetra-O-acetyl-6-O-trifluoromethanesulfonyl-ß-d-allopyranose. Furthermore, the practical yields of [18F]3FDA and [18F]6FDA using an automated synthesizer were also investigated. Radiochemical yields of 67% and 49% were obtained for [18F]3FDA and [18F]6FDA, respectively, in an automated synthesizer. As basic assessment of stability for use in PET scanning, high performance liquid chromatography analysis showed no decomposition of [18F]3FDA and [18F]6FDA after up to 6 h in rabbit blood plasma.


Assuntos
Radioisótopos de Flúor/química , Glucose/química , Glucose/síntese química , Compostos Radiofarmacêuticos/química , Compostos Radiofarmacêuticos/síntese química , Animais , Técnicas de Química Sintética , Estabilidade de Medicamentos , Marcação por Isótopo , Coelhos , Radioquímica , Compostos Radiofarmacêuticos/sangue
9.
Hell J Nucl Med ; 22(3): 200-205, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31587030

RESUMO

OBJECTIVE: This study was aimed to assess technical aspects of fractionation of commonly used cold kits in Nuclear Medicine. MATERIALS AND METHODS: A total of 90 samples (30 samples each) of technetium-99m methylene diphosphonate (99mTc-MDP), 99mTc-diethylenetriaminepentaacetic acid (DTPA) and 99mTc-dimercaptosuccinic acid (DMSA III) were taken on various days. The radiochemical purity was calculated of each fraction of these cold kits by using paper chromatography. RESULTS: The mean value of radiochemical purity of 99mTc -MDP, 99mTc -DTPA and 99mTc-DMSA(III) were calculated as ~ 95.12%, 91.43% and 95.68% and standard deviation (SD) were ~ 5.43, 8.36 and 3.88, respectively. Maximum time in which fractionation procedure completed i.e. time required for preparing the fraction or thawing was 10 minutes. All fractionated aliquots were between 1 and 15 days. Radiopharmaceutical bio-distribution was found to be appropriate during imaging in all samples. CONCLUSION: Fractionation of cold kits using standardised technique is a time and cost-effective method and does not deteriorate the quality of labelling in commonly used pharmaceuticals in our study. We have used fractionated aliquots up to 3 days of preparation in patients with clinically usable radiochemical purity. Deep frozen fractions can be used up to 15 days in our experience.


Assuntos
Custos e Análise de Custo , Radioquímica/economia , Radioquímica/métodos , Compostos Radiofarmacêuticos/química , Humanos , Controle de Qualidade , Radioquímica/instrumentação , Compostos Radiofarmacêuticos/farmacocinética , Solventes/química , Fatores de Tempo , Distribuição Tecidual , Tomografia Computadorizada de Emissão de Fóton Único
10.
Nucl Med Rev Cent East Eur ; 22(2): 56-59, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31482557

RESUMO

BACKGROUND: 44Sc is becoming attractive as a PET radionuclide due to its decay characteristics. It can be produced from 44Ca present in natural calcium with 2.08% abundance. MATERIALS AND METHODS: The targets were mostly prepared from natural CaCO3 or metallic calcium in the form of pellets. After irradiation they were dissolved in 3 M hydrochloric acid and 44Sc was separated from excess of calcium by precipitation of scandium hydroxide using ammonia. Alternatively, targets were dissolved in 11 M hydrochloric acid and 44Sc was separated by extraction chromatography on UTEVA resin. As the next step, in both processes 44Sc was further purified on a cation exchange resin. Initially, the separation procedures were developed with 46Sc as a tracer. Gamma spectrometry with a high purity germanium detector was used to determine the separation efficiency. Finally, the CaCO3 pellet with 99.2% enrichment in 44Ca was activated with protons via 44Ca(p,n)44Sc nuclear reaction. RESULTS: Altogether twenty two irradiations and separations were performed. The working procedures were developed and the quality of separated 44Sc solution was confirmed by radiolabeling of DOTATATE. The chemical purity of the product was sufficient for preclinical experiments. At the end of around 1 hour proton beam irradiation of CaCO3 pellet with 99.2% enrichment in 44Ca the obtained radioactivity of 44Sc was more than 4.8 GBq. CONCLUSION: 44Sc can be produced inexpensively with adequate yields and radionuclidic purity via 44Ca(p,n)44Sc nuclear reaction in small cyclotrons. The recovery yield in both investigated separation methods was comparable and amounted above 90%. The obtained 44Sc was pure in terms of radionuclide and chemical purity, as shown by the results of peptide radiolabeling.


Assuntos
Elementos da Série Actinoide/química , Precipitação Química , Hidróxidos/química , Radioquímica/métodos , Radioisótopos/química , Radioisótopos/isolamento & purificação , Escândio/química , Escândio/isolamento & purificação , Urânio/química , Carbonato de Cálcio/química , Ciclotrons , Marcação por Isótopo , Radioquímica/instrumentação
11.
Molecules ; 24(19)2019 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-31546683

RESUMO

Herein, we present a one-step labeling procedure of N-succinimidyl-4-[18F]-fluorobenzoate ([18F]SFB) starting from spirocyclic iodonium ylide precursors. Precursor syntheses succeeded via a simple one-pot, two-step synthesis sequence, in yields of approximately 25%. Subsequent 18F-nucleophilic aromatic labeling was performed, and radiochemical incorporations (RCCs) from 5-35% were observed. Purification could be carried out using HPLC and subsequent solid phase extraction. Radiochemical purity (RCP) of >95% was determined. The total synthesis time, including purification and formulation, was no longer than 60 min. In comparison to the established 3-step synthesis route of [18F]SFB, this one-step approach avoids formation of volatile radioactive side-products and simplifies automatization.


Assuntos
Radioisótopos de Flúor/química , Cromatografia Líquida de Alta Pressão , Tomografia por Emissão de Pósitrons , Radioquímica , Extração em Fase Sólida
12.
J Labelled Comp Radiopharm ; 62(13): 903-908, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31524293

RESUMO

In this practitioner protocol, the radiochemical synthesis of [11 C]CPPC is described in detail, and a quality control summary of three validation productions is presented. The results indicate that the radiotracer product can be produced in good radiochemical yield (> 60 mCi (2.22 GBq) at end-of-synthesis (EOS)), at high specific activity (molar activity > 11,435 mCi/µmole (423 GBq/µmole) at EOS) and high chemical and radiochemical purity. The entire production conforms to current Good Manufacturing Practice (cGMP) requirements. The final product is formulated as a sterile, pyrogen-free solution suitable for human injection.


Assuntos
Furanos/química , Furanos/síntese química , Microglia/metabolismo , Tomografia por Emissão de Pósitrons/métodos , Receptores de Fator Estimulador das Colônias de Granulócitos e Macrófagos/metabolismo , Biomarcadores/metabolismo , Técnicas de Química Sintética , Controle de Qualidade , Radioquímica
13.
J Labelled Comp Radiopharm ; 62(13): 874-884, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31495966

RESUMO

The clinical impact and accessibility of 99m Tc tracers for cancer diagnosis would be greatly enhanced by the availability of a new, simple, and easy labeling process and radiopharmaceuticals. 5-Fluorouracil is an antitumor drug, which has played an important role for the treatment of breast carcinoma. In the present study, a new derivative of 5-Fluorouracil was synthesized as (1-[{1'-(1''-deoxy-2'',3'':4'',5''-di-O-isopropylidene-ß-D-fructopyranose-1''-yl)-1'H-1',2', 3'-triazol-4'-yl}methyl]-5-fluorouracil) (E) and radiolabeled with 99m Tc. It was analyzed by radio thin layer chromatography for quality control and stability. The radiolabeled complex was subjected to in vitro cell-binding studies to determine healthy and cancer cell affinity using HaCaT and MCF-7 cells, respectively. In addition, in vitro cytotoxicity studies of compound E were performed with HaCaT and MCF-5 cells. The radiochemical purity of the [99m Tc]TcE was found to be higher than 90% at room temperature up to 6 hours. The radiolabeled complex showed higher specific binding to MCF-7 cells than HaCaT cells. IC50 values of E were found 31.5 ± 3.4 µM and 20.7 ± 2.77 µM for MCF-7 and HaCaT cells, respectively. The results demonstrated the potential of a new radiolabeled E with 99m Tc has selective for breast cancer cells.


Assuntos
Fluoruracila/química , Fluoruracila/metabolismo , Fluoruracila/toxicidade , Humanos , Concentração de Íons de Hidrogênio , Marcação por Isótopo , Células MCF-7 , Radioquímica , Tecnécio/química
14.
J Labelled Comp Radiopharm ; 62(11): 718-728, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31410877

RESUMO

This study aims at analyzing complexation properties of two new short somatostatin analogues, their synthesis, radiolabeling with 44 Sc, 207 Bi, and 152 Eu and stability in vitro. Short tetrapeptide Phe-d-Trp-Lys-Thr and pentapeptide Thz-Phe-d-Trp-Lys-Thr were first conjugated with the DOTA macrocyclic chelator. These conjugates were radiolabeled with 44 Sc, 207 Bi, and 152 Eu and characterized by thin-layer chromatography (TLC) and HPLC. The radiochemical purity was measured using digital autoradiography and gamma spectrometry. Optimum conditions of DOTA-conjugate labeling were found: 0.1mM, pH 8.0 to 8.4 at 90°C for DOTA-tetrapeptide complexes with 207 Bi and 152 Eu; 0.05mM, pH 4.0 to 5.0 at 90°C for 44 Sc-DOTA-tetrapeptide; 0.2mM, pH 4.0 to 5.0 at 90°C for 44 Sc-DOTA-pentapeptide. Complexes of DOTA-pentapeptide with 207 Bi and 152 Eu of radiochemical purity more than 95% were probably unstable at temperature higher than 37°C and were obtained at 37°C, pH 8.0 to 8.4 within 4 days. Mass spectra of the Eu-DOTA-pentapeptide revealed the presence of small fragments of the pentapeptide conjugate in the complex solution. in vitro stability studies were performed in saline in the presence of serum proteins and biologically relevant metal cations. All complexes demonstrated no cation release in vitro within 1 to 4 hours.


Assuntos
Octreotida/química , Octreotida/síntese química , Sequência de Aminoácidos , Animais , Estabilidade de Medicamentos , Compostos Heterocíclicos com 1 Anel/química , Marcação por Isótopo , Tomografia por Emissão de Pósitrons , Radioquímica , Compostos Radiofarmacêuticos/síntese química , Compostos Radiofarmacêuticos/química
15.
J Labelled Comp Radiopharm ; 62(12): 860-864, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31418468

RESUMO

We report an efficient protocol for the radiosynthesis of diastereomerically pure (E)-[11 C]ABP688, a positron emission tomography (PET) tracer for metabotropic glutamate type 5 (mGlu5) receptor imaging. The protocol reliably provides sterile and pyrogen-free formulation of (E)-[11 C]ABP688 suitable for preclinical and clinical PET imaging with >99% diastereomeric excess (d.e.), >99% overall radiochemical purity (RCP), 14.9 ± 4.3% decay-corrected radiochemical yield (RCY), and 148.86 ± 79.8 GBq/µmol molar activity in 40 minutes from the end of bombardment.


Assuntos
Radioisótopos de Carbono/química , Oximas/química , Oximas/síntese química , Piridinas/química , Piridinas/síntese química , Técnicas de Química Sintética , Tomografia por Emissão de Pósitrons , Radioquímica , Estereoisomerismo
16.
J Labelled Comp Radiopharm ; 62(12): 865-869, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31392740

RESUMO

18 O-labeled water (Water-18 O) is a widely used starting material of 18 F-labeled diagnostic agents in positron emission tomography (PET). Conventionally, Water-18 O has been separated from other stable oxygen isotope species (16 O, 17 O) by water distillation or nitric oxide distillation. However, conventional methods are costly and may have safety issues. In 2004, we developed the first unit of our novel oxygen isotope separation process by cryogenic oxygen distillation to overcome these issues. To meet the needs of the market, we built a second unit in 2013 and a third in 2016. We are now operating three commercially viable separation units with a total capacity of 600 kg of Water-18 O per year.


Assuntos
Indústrias , Isótopos de Oxigênio/isolamento & purificação , Radioquímica/métodos , Isótopos de Oxigênio/química , Radioquímica/instrumentação
17.
J Labelled Comp Radiopharm ; 62(12): 843-849, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31378967

RESUMO

The acyclic chelator HBED-CC has attained huge clinical significance owing to high thermodynamic and kinetic stability of 68 Ga-HBED-CC chelate. It provides an excellent platform for quick preparation of 68 Ga-based radiotracers in high yield. Thus, the present study aimed at conjugation of gastrin releasing peptide receptor (GRPr) antagonist, RM26, with HBED-CC chelator for 68 Ga-labeling. In vitro and vivo behavior of the peptide tracer, 68 Ga-HBED-CC-PEG2 -RM26, was assessed and compared with 68 Ga-NODAGA-PEG2 -RM26. The peptide tracers, 68 Ga-HBED-CC-PEG2 -RM26 and 68 Ga-NODAGA-PEG2 -RM26, prepared either by wet chemistry or formulated using freeze-dried kits exhibited excellent radiochemical yield and in vitro stability. The two peptide tracers cleared rapidly from the blood. Biodistribution studies in normal mice demonstrated slightly higher or comparable uptake of 68 Ga-HBED-CC-PEG2 -RM26 in GRPr-expressing organs pancreas, stomach, and intestine. The preliminary studies suggest high potential of 68 Ga-HBED-CC-PEG2 -RM26 for further investigation as a GRPr imaging agent and the wide scope of HBED-CC chelator in development of 68 Ga-based peptide tracers.


Assuntos
Ácido Edético/análogos & derivados , Radioisótopos de Gálio/química , Receptores da Bombesina/antagonistas & inibidores , Técnicas de Química Sintética , Ácido Edético/síntese química , Ácido Edético/química , Ácido Edético/farmacologia , Humanos , Interações Hidrofóbicas e Hidrofílicas , Marcação por Isótopo , Células PC-3 , Radioquímica
18.
J Labelled Comp Radiopharm ; 62(14): 920-924, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31379027

RESUMO

Parkinson disease (PD) is a neurodegenerative disorder characterized by the accumulation of α-synuclein into Lewy bodies. 3-Benzylidine-indolin-2-one represents a class of compounds, which are known to inhibit the accumulation of α-synuclein. In this paper, we report the synthesis of [13 C] and [15 N] labelled 1-benzyl-(Z)-3-(benzylidene)indolin-2-one from commercially available [13 C2 ]-chloroacetic acid and [15 N]-aniline in five steps. The product will be used to study its metabolites in human liver microsomes by liquid chromatography-tandem mass spectrometry.


Assuntos
Isótopos de Carbono/química , Indóis/química , Indóis/síntese química , Isótopos de Nitrogênio/química , Técnicas de Química Sintética , Humanos , Indóis/metabolismo , Microssomos Hepáticos/metabolismo , Radioquímica
19.
Nucl Med Biol ; 72-73: 11-19, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31255875

RESUMO

INTRODUCTION: O-(2-[18F]Fluoroethyl)-L-tyrosine ([18F]FET) is an established radiotracer used for oncology investigations by Positron Emission Tomography (PET). Main limitations to its widespread use are the synthesis itself (time; cost; radiochemical yield; complexity) and a troublesome and time-consuming HPLC purification. Aim of this work was to improve the preparation overall efficiency and, most important, to achieve an efficient and reliable purification by means of disposable cartridges. METHODS: [18F]FET was synthesized by direct nucleophilic radiofluorination of O-(2-tosyloxy-ethyl)-N-trityl-L-tyrosine t-butylester (TET) followed by acid hydrolysis with HCl. Several conditions and materials were tested for the synthesis and purification step. For the latter, a number of different commercial cartridges, varying in amount, particulate size and adsorbent, were examined. Best results were obtained by a combination of STRATA-X, tC18 and QMA cartridges. RESULTS: Starting from only 5 mg of TET, up to 11 GBq of injectable solutions of [18F]FET were produced within 36 min with 54-65% radiochemical yields and radiochemical purities >99%. No D-form was observed by chiral HPLC. Chemical purity was 1-2 order of magnitude below the limits imposed by the European Pharmacopoeia's monograph on [18F]FET. A radiochemical purity decrease by radiolysis, observed only on relatively large batches of [18F]FET, was efficiently suppressed by preloading in the receiving final vial a small amount of ethanol (<2% v/v). CONCLUSIONS: By combining improvements to a known synthetic route with a novel cartridge-based purification, [18F]FET was obtained in a very efficient and reproducible way. The whole process was easily implemented on a commercial automated module presently used for [18F]FDG production. ADVANCES IN KNOWLEDGE AND IMPLICATIONS FOR PATIENT CARE: A few drawbacks regarding the HPLC conditions recommended in the European Pharmacopoeia were highlighted. An alternative method able to cope with them is herein proposed The simplified preparation herein described is expected to encourage a more widespread clinical use of [18F]FET.


Assuntos
Compostos Radiofarmacêuticos/síntese química , Extração em Fase Sólida/métodos , Tirosina/análogos & derivados , Cromatografia Líquida de Alta Pressão , Humanos , Radioquímica , Compostos Radiofarmacêuticos/isolamento & purificação , Tirosina/síntese química , Tirosina/isolamento & purificação
20.
J Labelled Comp Radiopharm ; 62(12): 823-834, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31315149

RESUMO

Radiolabeled Arg-Gly-Asp (RGD) peptide derivatives have immense potential for non-invasive monitoring of malignancies overexpressing integrin αv ß3 receptors. Easy availability of suitable radiotracers would augment the utility of this class of molecular imaging agents. Towards this, the present article describes the development of an improved lyophilized kit for the routine clinical formulation of [99m Tc]Tc complex of HYNIC-conjugated dimeric cyclic RGD peptide derivative E-[c(RGDfK)]2 (E = glutamic acid, f = phenyl alanine, K = lysine) without using Sn2+ and systematic evaluation of its efficacy. Five batches of the kits were prepared, and [99m Tc]Tc-HYNIC-E[c(RGDfK)]2 radiotracer was synthesized with high radiochemical purity (98.6 ± 0.5%) and specific activity (124.8 GBq/µmol) using the kits. Biodistribution studies in C57BL/6 mice bearing melanoma tumor exhibited significant accumulation of the radiotracer in tumor (5.32 ± 0.56 %ID/g at 60 min p.i.), and this uptake was also found to be receptor-specific by blocking studies. Preliminary human clinical investigations carried out in 10 breast cancer patients revealed high radiotracer uptake in the tumor along with good tumor-to-background contrast. The developed kit formulation showed an exceptionally high shelf-life of at least 18 months. These results demonstrated promising attributes of the developed kit formulation and warrant more extensive clinical investigations.


Assuntos
Neoplasias da Mama/diagnóstico por imagem , Hidrazinas/química , Ácidos Nicotínicos/química , Compostos de Organotecnécio/química , Compostos de Organotecnécio/síntese química , Peptídeos Cíclicos/química , Tomografia Computadorizada com Tomografia Computadorizada de Emissão de Fóton Único/métodos , Adulto , Idoso , Animais , Técnicas de Química Sintética , Feminino , Meia-Vida , Humanos , Melanoma/diagnóstico por imagem , Melanoma/metabolismo , Camundongos , Pessoa de Meia-Idade , Compostos de Organotecnécio/farmacocinética , Radioquímica , Distribuição Tecidual
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