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1.
Nucl Med Biol ; 76-77: 1-9, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31520872

RESUMEN

INTRODUCTION: [68Ga]Ga-DATA-TOC is a new radiolabelled somatostatin-analogue for positron emission tomography (PET) imaging of neuroendocrine tumours. Its advantage over DOTA-conjugated compounds is the possibility for high-efficiency labelling with gallium-68 quickly at room temperature with high reliability and without the need for product purification, which enables the development of an instant kit-type labelling method. We evaluated its imaging characteristics in patients with neuroendocrine tumours in comparison to [68Ga]Ga-DOTA-TOC. METHODS: 19 patients imaged with [68Ga]Ga-DATA-TOC were retrospectively analysed and uptake in normal tissues was compared with a group of 19 patients imaged with [68Ga]Ga-DOTA-TOC. 10 patients imaged with [68Ga]Ga-DATA-TOC had a history of [68Ga]Ga-DOTA-TOC imaging before and were additionally analysed to obtain biodistribution data of both tracers in the same patients. In 5 patients showing stable disease between both examinations, tumour uptake, lesion detectability and lesion conspicuity of both tracers were evaluated. RESULTS: Uptake of [68Ga]Ga-DATA-TOC in normal organs with expression of the somatostatin receptor was 25-47% lower compared to [68Ga]Ga-DOTA-TOC. Background of [68Ga]Ga-DATA-TOC was 40-41% lower in the liver. A higher retention of [68Ga]Ga-DATA-TOC was observed in the blood (up to 67%) and in the lungs (up to 44%). Tumour uptake (SUV) was 22-31% lower for [68Ga]Ga-DATA-TOC. However, no significant differences were observed for tumour-to-background ratios and lesion detectability. Regarding liver metastases, [68Ga]Ga-DATA-TOC uptake (SUV) reached 69-73% of [68Ga]Ga-DOTA-TOC uptake, but tumour-to-background ratios of [68Ga]Ga-DATA-TOC were 105-110% of [68Ga]Ga-DOTA-TOC ratios. CONCLUSIONS, ADVANCES IN KNOWLEDGE AND IMPLICATIONS FOR PATIENT CARE: We demonstrated the feasibility of the new PET tracer [68Ga]Ga-DATA-TOC for imaging of patients with neuroendocrine tumours, showing a comparable performance to [68Ga]Ga-DOTA-TOC. [68Ga]Ga-DATA-TOC has the potential for development of an instant kit-type labelling method at room temperature similar to 99mTc-labelled radiopharmaceuticals, which might help to increase the availability of 68Ga-labelled somatostatin analogues for clinical routine use.


Asunto(s)
Tumores Neuroendocrinos/diagnóstico por imagen , Octreótido/análogos & derivados , Compuestos Organometálicos , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Somatostatina/análogos & derivados , Anciano , Femenino , Humanos , Masculino , Tumores Neuroendocrinos/metabolismo , Octreótido/química , Octreótido/farmacocinética , Compuestos Organometálicos/química , Compuestos Organometálicos/farmacocinética , Radioquímica , Estudios Retrospectivos , Somatostatina/química , Somatostatina/farmacología , Distribución Tisular
2.
Nuklearmedizin ; 57(1): 4-17, 2018 02.
Artículo en Alemán | MEDLINE | ID: mdl-29536494

RESUMEN

The present guideline is focused on quality assurance of somatostatin receptor PET/CT (SSTR-PET/CT) in oncology patients. The document has been developed by a multidisciplinary board of specialists providing consensus of definitions, prerequisites, methodology, operating procedures, assessment, and standardized reporting. In particular, imaging procedures for the two most commonly used radioligands of human SSTR, i. e. 68Ga-DOTATOC and 68Ga-DOTATATE are presented. Overall, SSTR-PET/CT requires close interdisciplinary communication and cooperation of referring and executing medical disciplines, taking into account existing guidelines and recommendations of the European and German medical societies, including the European Association of Nuclear Medicine (EANM), German Society for Endocrinology (DGE), German Society for Nuclear Medicine (DGN) and German Society for Radiology (DRG).


Asunto(s)
Tomografía Computarizada por Tomografía de Emisión de Positrones , Guías de Práctica Clínica como Asunto , Receptores de Somatostatina/metabolismo , Humanos , Neoplasias/diagnóstico por imagen , Neoplasias/metabolismo , Radiofármacos
3.
Neuroscience ; 374: 187-204, 2018 03 15.
Artículo en Inglés | MEDLINE | ID: mdl-29421436

RESUMEN

Parkinson's disease (PD) is characterized by a degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNpc) that causes a dopamine (DA) deficit in the caudate-putamen (CPu) accompanied by compensatory changes in other neurotransmitter systems. These changes result in severe motor and non-motor symptoms. To disclose the role of various receptor binding sites for DA, noradrenaline, and serotonin in the hemiparkinsonian (hemi-PD) rat model induced by unilateral 6-hydroxydopamine (6-OHDA) injection, the densities of D1, D2/D3, α1, α2, and 5HT2A receptors were longitudinally visualized and measured in the CPu of hemi-PD rats by quantitative in vitro receptor autoradiography. We found a moderate increase in D1 receptor density 3 weeks post lesion that decreased during longer survival times, a significant increase of D2/D3 receptor density, and 50% reduction in 5HT2A receptor density. α1 receptor density remained unaltered in hemi-PD and α2 receptors demonstrated a slight right-left difference increasing with post lesion survival. In a second step, the possible role of receptors on the known reduction of apomorphine-induced rotations in hemi-PD rats by intrastriatally injected Botulinum neurotoxin-A (BoNT-A) was analyzed by measuring the receptor densities after BoNT-A injection. The application of this neurotoxin reduced D2/D3 receptor density, whereas the other receptors mainly remained unaltered. Our results provide novel data for an understanding of the postlesional plasticity of dopaminergic, noradrenergic and serotonergic receptors in the hemi-PD rat model. The results further suggest a therapeutic effect of BoNT-A on the impaired motor behavior of hemi-PD rats by reducing the interhemispheric imbalance in D2/D3 receptor density.


Asunto(s)
Antiparkinsonianos/farmacología , Toxinas Botulínicas Tipo A/farmacología , Cuerpo Estriado/efectos de los fármacos , Trastornos Parkinsonianos/tratamiento farmacológico , Receptores de Neurotransmisores/metabolismo , Animales , Apomorfina/farmacología , Cuerpo Estriado/metabolismo , Cuerpo Estriado/patología , Agonistas de Dopamina/farmacología , Lateralidad Funcional , Estudios Longitudinales , Masculino , Actividad Motora/efectos de los fármacos , Actividad Motora/fisiología , Neurotoxinas/farmacología , Oxidopamina , Trastornos Parkinsonianos/metabolismo , Trastornos Parkinsonianos/patología , Ratas Wistar
4.
Dalton Trans ; 45(4): 1398-409, 2016 Jan 28.
Artículo en Inglés | MEDLINE | ID: mdl-26675416

RESUMEN

The complexation ability of DOTA analogs bearing one methylenephosphonic (DO3AP) or methylenephosphinic (DO3AP(PrA) and DO3AP(ABn)) acid pendant arm toward scandium was evaluated. Stability constants of their scandium(iii) complexes were determined by potentiometry combined with (45)Sc NMR spectroscopy. The stability constants of the monophosphinate analogues are somewhat lower than that of the Sc-DOTA complex. The phosphorus acid moiety interacts with trivalent scandium even in very acidic solutions forming out-of-cage complexes; the strong affinity of the phosphonate group to Sc(iii) precludes stability constant determination of the Sc-DO3AP complex. These results were compared with those obtained by the free-ion selective radiotracer extraction (FISRE) method which is suitable for trace concentrations. FISRE underestimated the stability constants but their relative order was preserved. Nonetheless, as this method is experimentally simple, it is suitable for a quick relative comparison of stability constant values under trace concentrations. Radiolabelling of the ligands with (44)Sc was performed using the radioisotope from two sources, a (44)Ti/(44)Sc generator and (44m)Sc/(44)Sc from a cyclotron. The best radiolabelling conditions for the ligands were pH = 4, 70 °C and 20 min which were, however, not superior to those of the parent DOTA. Nonetheless, in vitro behaviour of the Sc(iii) complexes in the presence of hydroxyapatite and rat serum showed sufficient stability of (44)Sc complexes of these ligands for in vivo applications. PET images and ex vivo biodistribution of the (44)Sc-DO3AP complex performed on healthy Wistar male rats showed no specific bone uptake and rapid clearance through urine.


Asunto(s)
Compuestos Heterocíclicos con 1 Anillo/química , Compuestos Organometálicos/síntesis química , Ácidos Fosforosos/química , Escandio/química , Termodinámica , Titanio/química , Animales , Ligandos , Espectroscopía de Resonancia Magnética , Masculino , Estructura Molecular , Compuestos Organometálicos/química , Potenciometría , Radioisótopos/química , Ratas , Ratas Wistar
5.
Neuroscience ; 311: 539-51, 2015 Dec 17.
Artículo en Inglés | MEDLINE | ID: mdl-26546471

RESUMEN

Parkinson's disease (PD) is a well-characterized neurological disorder with regard to its neuropathological and symptomatic appearance. At the genetic level, mutations of particular genes, e.g. Parkin and DJ-1, were found in human hereditary PD with early onset. Neurotransmitter receptors constitute decisive elements in neural signal transduction. Furthermore, since they are often altered in neurological and psychiatric diseases, receptors have been successful targets for pharmacological agents. However, the consequences of PD-associated gene mutations on the expression of transmitter receptors are largely unknown. Therefore, we studied the expression of 16 different receptor binding sites of the neurotransmitters glutamate, GABA, acetylcholine, adrenaline, serotonin, dopamine and adenosine by means of quantitative receptor autoradiography in Parkin and DJ-1 knockout mice. These knockout mice exhibit electrophysiological and behavioral deficits, but do not show the typical dopaminergic cell loss. We demonstrated differential changes of binding site densities in eleven brain regions. Most prominently, we found an up-regulation of GABA(B) and kainate receptor densities in numerous cortical areas of Parkin and DJ-1 knockout mice, as well as increased NMDA but decreased AMPA receptor densities in different brain regions of the Parkin knockout mice. The alterations of three different glutamate receptor types may indicate the potential relevance of the glutamatergic system in the pathogenesis of PD. Furthermore, the cholinergic M1, M2 and nicotinic receptors as well as the adrenergic α2 and the adenosine A(2A) receptors showed differentially increased densities in Parkin and DJ-1 knockout mice. Taken together, knockout of the PD-associated genes Parkin or DJ-1 results in differential changes of neurotransmitter receptor densities, highlighting a possible role of altered non-dopaminergic, and in particular of glutamatergic neurotransmission in PD pathogenesis.


Asunto(s)
Encéfalo/metabolismo , Proteínas Oncogénicas/genética , Peroxirredoxinas/genética , Receptores de Neurotransmisores/metabolismo , Ubiquitina-Proteína Ligasas/genética , Animales , Autorradiografía , Encéfalo/patología , Masculino , Ratones Endogámicos C57BL , Ratones Noqueados , Proteínas Oncogénicas/deficiencia , Trastornos Parkinsonianos/metabolismo , Trastornos Parkinsonianos/patología , Peroxirredoxinas/deficiencia , Proteína Desglicasa DJ-1 , Ubiquitina-Proteína Ligasas/deficiencia
6.
Nuklearmedizin ; 54(1): 1-11; quiz N2, 2015.
Artículo en Alemán | MEDLINE | ID: mdl-25683107

RESUMEN

This document describes the guideline for peptide receptor radionuclide therapy (PRRT) published by the German Society of Nuclear Medicine (DGN) and accepted by the Association of the Scientific Medical Societies in Germany (AWMF) to be included in the official AWMF Guideline Registry. These recommendations are a prerequisite for the quality management in the treatment of patients with somatostatin receptor expressing tumours using PRRT. They are aimed at guiding nuclear medicine specialists in selecting likely candidates to receive PRRT and to deliver the treatment in a safe and effective manner. The recommendations are based on an interdisciplinary consensus. The document contains background information and definitions and covers the rationale, indications and contraindications for PRRT. Essential topics are the requirements for institutions performing the therapy, e. g. presence of an expert for medical physics, intense cooperation with all colleagues involved in the treatment of a patient, and a certificate of instruction in radiochemical labelling and quality control are required. Furthermore, it is specified which patient data have to be available prior to performance of therapy and how treatment has to be carried out technically. Here, quality control and documentation of labelling are of great importance. After treatment, clinical quality control is mandatory (work-up of therapy data and follow-up of patients). Essential elements of follow-up are specified in detail. The complete treatment inclusive after-care has to be realised in close cooperation with the involved medical disciplines. Generally, the decision for PRRT should be undertaken within the framework of a multi-disciplinary tumour board.


Asunto(s)
Neoplasias/metabolismo , Neoplasias/radioterapia , Péptidos/farmacocinética , Oncología por Radiación/normas , Radiofármacos/uso terapéutico , Receptores de Somatostatina/metabolismo , Alemania , Humanos , Guías de Práctica Clínica como Asunto , Radiofármacos/farmacocinética
7.
Neuroscience ; 285: 11-23, 2015 Jan 29.
Artículo en Inglés | MEDLINE | ID: mdl-25451278

RESUMEN

Parkinson's disease (PD) is the second most common neurodegenerative disorder, characterized by alterations of nigrostriatal dopaminergic neurotransmission. Compared to the wealth of data on the impairment of the dopamine system, relatively limited evidence is available concerning the role of major non-dopaminergic neurotransmitter systems in PD. Therefore, we comprehensively investigated the density and distribution of neurotransmitter receptors for glutamate, GABA, acetylcholine, adrenaline, serotonin, dopamine and adenosine in brains of homozygous aphakia mice being characterized by mutations affecting the Pitx3 gene. This genetic model exhibits crucial hallmarks of PD on the neuropathological, symptomatic and pharmacological level. Quantitative receptor autoradiography was used to characterize 19 different receptor binding sites in eleven brain regions in order to understand receptor changes on a systemic level. We demonstrated striking differential changes of neurotransmitter receptor densities for numerous receptor types and brain regions, respectively. Most prominent, a strong up-regulation of GABA receptors and associated benzodiazepine binding sites in different brain regions and concomitant down-regulations of striatal nicotinic acetylcholine and serotonergic receptor densities were found. Furthermore, the densities of glutamatergic kainate, muscarinic acetylcholine, adrenergic α1 and dopaminergic D2/D3 receptors were differentially altered. These results present novel insights into the expression of neurotransmitter receptors in Pitx3(ak) mice supporting findings on PD pathology in patients and indicating on the possible underlying mechanisms. The data suggest Pitx3(ak) mice as an appropriate new model to investigate the role of neurotransmitter receptors in PD. Our study highlights the relevance of non-dopaminergic systems in PD and for the understanding of its molecular pathology.


Asunto(s)
Encéfalo/metabolismo , Proteínas de Homeodominio/metabolismo , Trastornos Parkinsonianos/metabolismo , Receptores de Neurotransmisores/metabolismo , Factores de Transcripción/metabolismo , Acetilcolina/metabolismo , Adenosina/metabolismo , Animales , Dopamina/metabolismo , Epinefrina/metabolismo , Proteínas de Homeodominio/genética , Homocigoto , Masculino , Ratones Endogámicos C57BL , Ratones Transgénicos , Serotonina/metabolismo , Factores de Transcripción/genética , Ácido gamma-Aminobutírico/metabolismo
8.
Recent Results Cancer Res ; 194: 3-16, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-22918751

RESUMEN

In 1964, first (68)Ge/(68)Ga radionuclide generators were described. Although the generator design was by far not adequate to our today's level of chemical, radiopharmaceutical and medical expectations, it perfectly met the needs of molecular imaging of this period. (68)Ga-EDTA as directly eluted from the generators entered the field of functional diagnosis, in particular for brain imaging. A new type of generators became commercially available in the first years of the 21st century. Generator eluates based on hydrochloric acid provided "cationic" (68)Ga instead of "inert" (68)Ga-complexes and opened new pathways of Me(III) based radiopharmaceutical chemistry. The impressive success of utilizing (68)Ga- DOTA-octreotides and PET/CT instead of e.g., (111)In-DTPA-octreoscan and SPECT paved the way not only towards clinical acceptance of this particular tracer for imaging neuroendocrine tracers, but to the realisation of the great potential of the (68)Ge/(68)Ga generator for modern nuclear medicine in general. The last decade has seen a (68)Ga rush. Increasing applications of generator based (68)Ga radiopharmaceuticals (for diagnosis alone, but increasingly for treatment planning thanks to the inherent option as expressed by THERANOSTICS), now ask for further developments - towards the optimization of (68)Ge/(68)Ga generators both from chemical and regulatory points of view. Dedicated chelators may be required to broaden the feasibility of (68)Ga labeling of more sensitive targeting vectors and generator chemistry may be adopted to those chelators - or vice versa. This review describes the development and the current status of (68)Ge/(68)Ga radionuclide generators.


Asunto(s)
Radioisótopos de Galio/aislamiento & purificación , Generadores de Radionúclidos , Radiofármacos
9.
Recent Results Cancer Res ; 194: 33-42, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-22918753

RESUMEN

New (68)Ge/(68)Ga radionuclide generators provide the positron emitter (68)Ga (T½ = 67.7 min) as an easily available and relatively inexpensive source of a PET nuclide for labeling of interesting targeting vectors. However, currently available "ionic" (68)Ge/(68)Ga radionuclide generators are not necessarily optimized for the routine synthesis of (68)Ga-labeled radiopharmaceuticals in a clinical environment. Post-processing of (68)Ge/(68)Ga generators using cation exchange resins provides chemically and radiochemically pure (68)Ga with 97±2% within less than 4 min, with (68)Ge almost completely removed, and ready for online labeling. This simple, fast, and efficient technology can be extended for new applications. The options are (a) to transfer (68)Ga from the cation exchange resin onto an anion exchange resin, to remove acetone, and to further purify the (68)Ga, (b) to obtain (68)Ga in pure non-aqueous solution via (68)Ga(acac)(3) as a synthon for syntheses in organic solvents, and (c) to create an option toward instantaneous determination of (68)Ge breakthrough, what may be required prior to the release of (68)Ga radiopharmaceutical preparations.


Asunto(s)
Resinas de Intercambio de Catión/química , Radioisótopos de Galio/aislamiento & purificación , Generadores de Radionúclidos , Radiofármacos/síntesis química
10.
Appl Radiat Isot ; 76: 24-30, 2013 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-23245638

RESUMEN

(68)Ga represents one of the very early radionuclides applied to positron emission tomography (PET) imaging at a time when even the wording PET itself was not established. Today it faces a renaissance in terms of new (68)Ge/(68)Ga radionuclide generators, sophisticated (68)Ga radiopharmaceuticals, and state-of-the-art clincial diagnoses via positron emission tomography/computed tomography (PET/CT). Thanks to the pioneering achievement of radiochemists in Obninsk, Russia, a new type of (68)Ge/(68)Ga generators became commercially available in the first years of the 21st century. Generator eluates based on hydrochloric acid provided "cationic" (68)Ga instead of "inert" (68)Ga-complexes, opening new pathways of Me(III) based radiopharmaceutical chemistry. Consequently, the last decade has seen a (68)Ga rush. Increasing applications of generator based (68)Ga radiopharmaceuticals (for diagnosis alone, but increasingly for treatment planning, thanks to the inherent option as expressed by THERANOSTICS, ask for new developments towards the optimisation of (68)Ge/(68)Ga generators both from chemical and regulatory points of view.


Asunto(s)
Radioisótopos de Galio/química , Generadores de Radionúclidos , Radiofármacos/química , Imagen Multimodal , Tomografía de Emisión de Positrones , Radiofármacos/aislamiento & purificación , Tomografía Computarizada por Rayos X
11.
Nucl Med Biol ; 39(7): 993-9, 2012 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-22633217

RESUMEN

PURPOSE: Bone metastases are a serious aggravation for patients suffering from cancer. Therefore, early recognition of bone metastases is of great interest for further treatment of patients. Bisphosphonates are widely used for scintigraphy of bone lesions with (99m)Tc. Using the (68)Ge/(68)Ga generator together with a macroyclic bisphosphonate a comparable PET-tracer comes into focus. PROCEDURES: The bisphosphonate DOTA-conjugated ligand BPAMD was labelled with (68)Ga. [(68)Ga]BPAMD was evaluated in vitro concerning binding to hydroxyapatite and stability. The tracer's in vivo accumulation was determined on healthy rats and bone metastases bearing animals by µ-PET. RESULTS: BPAMD was labelled efficiently with (68)Ga after 10 min at 100°C. [(68)Ga]BPAMD showed high in vitro stability within 3h and high binding to hydroxyapatite. Consequently, µ-PET experiments revealed high accumulation of [(68)Ga]BPAMD in regions of pronounced remodelling activity like bone metastases. CONCLUSIONS: (68)Ga BPAMD reveals great potential for diagnosis of bone metastases via PET/CT. The straight forward (68)Ga-labelling could be transferred to a kit-preparation of a cyclotron-independent PET tracer instantaneously available in many clinical sites using the (68)Ge/(68)Ga generator.


Asunto(s)
Neoplasias Óseas/diagnóstico por imagen , Neoplasias Óseas/secundario , Difosfonatos/química , Electrones , Compuestos Heterocíclicos con 1 Anillo/química , Tomografía de Emisión de Positrones/métodos , Animales , Línea Celular Tumoral , Difosfonatos/metabolismo , Durapatita/metabolismo , Radioisótopos de Galio , Compuestos Heterocíclicos con 1 Anillo/metabolismo , Masculino , Radioquímica , Ratas
12.
Appl Radiat Isot ; 69(7): 942-6, 2011 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-21420306

RESUMEN

An improved chemical strategy for processing of the generator produced (68)Ga was developed based on processing of the original (68)Ge/(68)Ga generator eluate on a micro-column. Direct pre-concentration and purification of the eluted (68)Ga is performed on a cation-exchange resin in hydrochloric acid/acetone media. A supplementary step based on a second micro-column filled with a second resin allows direct re-adsorption of (68)Ga eluted from the cation exchanger. (68)Ga is finally striped from the second resin with a small volume of pure water. For this purpose a strong anion exchanger and a novel extraction chromatographic resin based on tetraalkyldiglycolamides are characterized. The strategy allows online pre-concentration and purification of (68)Ga from the original generator eluate. The supplementary column allows transferring (68)Ga with high radionuclide and chemical quality in the aqueous solution with small volume and low acidity useful for direct radiolabeling reactions.

13.
Appl Radiat Isot ; 68(9): 1636-41, 2010 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-20434351

RESUMEN

The (44)Ti/(44)Sc (T(1/2)(44)Ti=60a) generator provides cyclotron-independent access to positron-emitting (44)Sc (T(1/2)=3.97d) for PET imaging. This work aims to post-elution processing of initial (44)Sc generator eluates in order to reduce its volume, HCl concentration and remove the oxalate anions. The on-line adsorption of (44)Sc on cationic resin AG 50W-X8 (200-400 mesh, H(+)-form) is achieved with >98% efficacy. Subsequently, the purified (44)Sc is desorbed by using 3ml of 0.25M ammonium acetate (pH=4.0). The post-processing takes 10min. The overall yield of the post-processing reached 90%, which is referred to the (44)Sc obtained from the (44)Ti/(44)Sc generator. In addition to the chemical purification, the content of (44)Ti breakthrough was further reduced by one order of magnitude. The 185MBq generator finally provides 150MBq of (44)Sc containing <10Bq of (44)Ti ready for labeling.


Asunto(s)
Tomografía de Emisión de Positrones/métodos , Radioisótopos/química , Radioisótopos/aislamiento & purificación , Radiofármacos/síntesis química , Radiofármacos/aislamiento & purificación , Escandio/química , Escandio/aislamiento & purificación , Titanio/química , Marcaje Isotópico/métodos , Titanio/aislamiento & purificación
14.
Bioorg Med Chem ; 15(9): 3171-5, 2007 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-17346977

RESUMEN

[(18)F]Fluoroethylcholine has been recently introduced as a promising (18)F-labelled analogue of [(11)C]choline which had been previously described as a tracer for metabolic cancer imaging with positron emission tomography (PET). Due to the practical advantages of using the longer-lived radioisotope (18)F (t(1/2)=110 min), offering the opportunity of a more widespread clinical application, we established a reliable, fully automated synthesis for its production using a modified, commercially available module. [(18)F]Fluoroethylcholine was prepared from N,N-dimethylaminoethanol by iodide catalyzed alkylation with 1-[(18)F]fluoro-2-tosylethane as alkylating agent, resulting in a total radiochemical yield of 30+/-6% after a synthesis time of 50 min. The specific activity of [(18)F]fluoroethylcholine was >55 GBq/micromol and the radiochemical purity 95-99%.


Asunto(s)
Colina/análogos & derivados , Neoplasias/diagnóstico , Colina/síntesis química , Colina/química , Cromatografía Líquida de Alta Presión/instrumentación , Cromatografía Líquida de Alta Presión/métodos , Radioisótopos de Flúor , Estructura Molecular , Sensibilidad y Especificidad
15.
Eur J Nucl Med Mol Imaging ; 32(11): 1324-8, 2005 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-16133376

RESUMEN

PURPOSE: The new beta2 radioligand (R,R)(S,S) 5-(2-(2-[4-(2-[18F]fluoroethoxy)phenyl]-1-methylethylamino)-1-hydroxyethyl)-benzene-1,3-diol ([18F]FE-fenoterol; [18F]FEFE), a fluoroethylated derivative of racemic fenoterol, was evaluated in vivo and ex vivo using a guinea pig model. METHODS: Dynamic PET studies over 60 min with [(18)F]FEFE were performed in nine Hartley guinea pigs in which a baseline (group 1, n=3), a predose (group 2, n=3; 2 mg/kg fenoterol 5 min prior to injection of [18F]FEFE) or a displacement study (group 3, n=3; 2 mg/kg fenoterol 5 min post injection of [18F]FEFE) was conducted. RESULTS: In all animal groups, the lungs could be visualised and semi-quantified separately by calculating uptake ratios to non-specific binding in the neck area. Premedication with non-radioactive fenoterol and displacement tests showed significant reduction of lung uptake, by 94% and 76%, respectively. CONCLUSION: These data demonstrate specific binding of the new radioligand to the pulmonary beta2-receptors in accordance with ex vivo measurements. Therefore, [18F]FEFE seems to be suitable for the in vivo visualisation and quantification of the pulmonary beta2-receptor binding in this animal model.


Asunto(s)
Fenoterol/análogos & derivados , Pulmón/diagnóstico por imagen , Pulmón/metabolismo , Receptores Adrenérgicos beta 2/metabolismo , Animales , Estudios de Factibilidad , Fenoterol/farmacocinética , Cobayas , Tasa de Depuración Metabólica , Modelos Animales , Especificidad de Órganos , Cintigrafía , Radiofármacos/farmacocinética , Distribución Tisular
17.
Exp Clin Endocrinol Diabetes ; 113(7): 388-95, 2005 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-16025400

RESUMEN

Pancreatic islet cell mass (PICM) is a major determinant of the insulin secretory capacity in humans. Currently, the only method for accurate assessment of the PICM is an autopsy study. Thus, development of a technique allowing the non-invasive quantification of PICM is of great interest. The aim of this study was to develop such a non-invasive technique featuring novel fluorine- and (99m)Tc-labelled glibenclamide derivatives. Despite the structural modifications necessary to introduce fluorine into the glibenclamide molecule, all derivatives retained insulin stimulating capacity as well as high affinity binding to human SUR1 when compared to the original glibenclamide. Contrastingly, the lipophilicity of the fluorine-labelled derivatives was altered depending on the particular modification. In the human PET-study a constant but weak radioactive signal could be detected in the pancreas using a fluorine-labelled glibenclamide derivative. However, a reliable assessment and visualisation of the PICM could not be obtained. It can be assumed that the high uptake of the fluorine-labelled tracer e.g. into the the liver and the high plasma protein binding leads to a relatively low signal-to-noise ratio. In case of the presented fluorine-labelled glibenclamide based compounds this could be the result of their invariably high lipophilicity. The development of a (99 m)Tc-labelled glibenclamide derivative with a lower lipophilicity and differing in vivo behaviour, glibenclamide based compounds for non-invasive imaging of the pancreatic islet cell mass may be possible.


Asunto(s)
Diabetes Mellitus/diagnóstico por imagen , Radioisótopos de Flúor , Gliburida/análogos & derivados , Hipoglucemiantes , Islotes Pancreáticos/diagnóstico por imagen , Radiofármacos , Tecnecio , Transportadoras de Casetes de Unión a ATP/metabolismo , Animales , Gliburida/síntesis química , Gliburida/farmacocinética , Humanos , Hipoglucemiantes/síntesis química , Hipoglucemiantes/farmacocinética , Insulina/metabolismo , Islotes Pancreáticos/efectos de los fármacos , Islotes Pancreáticos/metabolismo , Imagen por Resonancia Magnética , Tomografía de Emisión de Positrones , Canales de Potasio/metabolismo , Canales de Potasio de Rectificación Interna/metabolismo , Radiofármacos/síntesis química , Radiofármacos/farmacocinética , Ratas , Ratas Sprague-Dawley , Receptores de Droga/metabolismo , Receptores de Sulfonilureas
18.
Appl Radiat Isot ; 63(3): 343-51, 2005 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-15955705

RESUMEN

Radioarsenic labelled radiopharmaceuticals could be a valuable asset to Positron Emission Tomography (PET). In particular, the long half-lives of (72)As (T(1/2)=26 h) and (74)As (T(1/2)=17.8 d) allow to investigate slow physiological or metabolical processes, like the enrichment and distribution of antibodies in tumor tissue. This work describes the direct production of no-carrier-added (nca) arsenic isotopes *As, with *=71, 72, 73, 74 or 77, the reaction to [*As]AsI(3) and its radiochemical separation from the irradiated solid germanium oxide via polystyrene-based solid-phase extraction. The germanium oxide target, irradiated at a cyclotron or a nuclear reactor, is dissolved in concentrated HF and Ge is separated almost quantitatively (99.97%) as [GeF(6)](2-). [*As]AsI(3) is formed by addition of potassium iodide. The radiochemical separation yield for arsenic is >90%. [*As]AsI(3) is a versatile radioarsenic labelling synthon.


Asunto(s)
Arsénico/aislamiento & purificación , Germanio/química , Radioisótopos/aislamiento & purificación , Radiofármacos/síntesis química , Semivida , Tomografía de Emisión de Positrones/métodos
19.
Appl Radiat Isot ; 62(5): 711-20, 2005 May.
Artículo en Inglés | MEDLINE | ID: mdl-15763477

RESUMEN

The potential tumor seeking MRI contrast agent MnTPPS(4) was labelled with the positron emitting nuclide (51)Mn in no-carrier-added (n.c.a.) form. The complex formation kinetics were investigated and the apparent rate constants were determined under pseudo-first-order conditions. The derived bimolecular rate constants gave the Arrhenius parameters E(A)=84 kJ mol(-1) and A=2 x 10(12)s(-1)M(-1). Optimum labelling conditions were derived (radiochemical yields >99% possible, effective yields about 32%). Separation and purification of n.c.a. (51)MnTPPS(4) were performed for potential human use. All impurities were <1%.


Asunto(s)
Medios de Contraste/química , Imagen por Resonancia Magnética , Manganeso/química , Porfirinas/química , Humanos , Cinética , Neoplasias/diagnóstico , Porfirinas/aislamiento & purificación
20.
Appl Radiat Isot ; 62(3): 451-6, 2005 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-15607923

RESUMEN

The low-energy electron spectra generated in the decay of 140Nd have been measured using a combined electrostatic spectrometer adjusted to the 4, 7, and 35 eV instrumental resolution. In order to estimate the therapeutic potential of low-energy electrons associated with the decay of 140Nd, similar experiments have been performed with 111In. Relative Auger electron intensity ratios per decay are: 111In(K-Auger)/140Nd(K-Auger)=1.47(12), 111In(L-Auger) /140Nd(L-Auger)=1.1(4), and 111In(L-Auger [2.8-7 keV])/140Nd(L-Auger [2.8-7 keV])=0.24(11). The obtained K-Auger group intensity ratios have been compared with results of calculations. The good agreement found for the experimental and estimated values indicates that such information can be also derived using available nuclear and atomic data. The relative intensity of L-Auger electrons emitted within the 2.8-7 keV interval is higher for 140Nd by a factor of about 4 compared to 111In. As the L-Auger emission is dominating relative to that of the K-Auger group, this implicates that any potential endotherapeutic strategy using 140Nd-labelled targeting vectors requires a maximum accumulation of the endoradiotherapeutical close to the cell nucleus or the DNA of the tumour cell.


Asunto(s)
Neodimio/química , Radioisótopos/química , ADN de Neoplasias/efectos de la radiación , Neodimio/farmacología , Radioisótopos/farmacología , Neoplasias de los Tejidos Blandos/radioterapia , Análisis Espectral
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