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Alfons Verbruggen

Publications and source records attributed to Alfons Verbruggen.

15 recordsLinked to original sources
PubMed2006

Magnetic resonance imaging after radiofrequency ablation in a rodent model of liver tumor: tissue characterization using a novel necrosis-avid contrast agent.

We exploited a necrosis-avid contrast agent ECIV-7 for magnetic resonance imaging (MRI) in rodent liver tumors after radiofrequency ablation (RFA). Rats bearing liver rhabdomyosarcoma (R1) were randomly allocated to three groups: group I, complete RFA, group II, incomplete RFA, and group III, sham ablation. Within 24 h after RFA, T1-weighted (T1-w) MRI was performed before and after injection of ECIV-7 at 0.05 mmol/kg and followed up from 6-24 h. Signal intensities (SIs) were measured with relative enhancement (RE) and contrast ratio (CR) calculated. The MRI findings were verified histomorphologically. On plain T1-w MRI the contrasts between normal liver, RFA lesion, residual and/or intact tumor were vague. Early after administration of ECIV-7, the liver SI was strongly enhanced (RE=40-50%), leaving the RFA lesion as a hypointense region in groups I and II. At delayed phase, two striking peri-ablational enhancement patterns appeared (RE=90% and CR=1.89%), i.e., "O" type of hyperintense rim in group I and "C" type of incomplete rim in group II. These MRI manifestations could be proven histologically. In this study, tissue components after RFA could be characterized with discernable contrasts by necrosis-avid contrast agent (NACA)-enhanced MRI, especially at delayed phase. This approach may prove useful for defining the ablated area and identifying residual tumor after RFA.

Animals↗
PubMed2006

The effect of a methyl or 2-fluoroethyl substituent at the N-3 position of thymidine, 3'-fluoro-3'-deoxythymidine and 1-beta-D-arabinosylthymine on their antiviral and cytostatic activity in cell culture.

Thymidine (Thd), 1-beta-D-arabinosylthymine (ara-T) and 3'-fluoro-3'-deoxythymidine (FLT) have been substituted at N-3 by a methyl or a 2-fluoroethyl group. FLT and ara-T are markedly inhibitory against human immunodeficiency virus type 1 (HIV-1) and HIV-2, and herpes simplex virus type 1 (HSV-1) and HSV-2, respectively. Modification at N-3 of these compounds markedly decreases both the antiviral and cytostatic activity of the parent compounds FLT and ara-T except for N-3-(methyl)-Thd that proved highly cytostatic for murine leukaemia L1210 cells. The decreased biological activity of the N-3-substituted pyrimidine nucleoside analogues coincides with a significantly lower affinity of the modified Thd analogues for the cellular and viral (activating) nucleoside kinases.

Animals↗
PubMed2006

The impact of aggregation on the biodistribution of hypericin.

Hypericin is a potent agent in the photodynamic therapy of cancers and accumulates to a large extent in tumor tissue. To better understand the impact of hypericin aggregates present in the delivery vehicle on the biodistribution of the compound, we compared the in vivo tissue accumulation after administering hypericin suspended as coarse aggregates in phosphate-buffered saline, with the biodistribution found after injection of a solution of hypericin in a mixture of DMSO, polyethylene glycol and water. When administered as coarse aggregates, hypericin showed a pronounced uptake in liver, spleen and lung and a slow body clearance with a complete decline in tumor/normal tissue ratios (far less than 1). In contrast, delivery of hypericin as a solution resulted in dramatically improved tumor to normal tissue ratios and a relatively fast elimination from the body. To elucidate the exact localization of hypericin in both conditions, a fluorescence microscopy study was performed on sections of spleen, liver, lung and tumor tissue. At 24 h after injection, fluorescence in spleen, liver and lung was faint and homogeneous for dissolved hypericin, whereas bright fluorescent spots covering the entire tissue sections were found when coarse aggregates were injected. We found that aggregates get trapped within these tissues, followed by a gradual monomerization. A direct involvement of monocytes and macrophages, however, could not be demonstrated. In conclusion, it is of critical importance that the delivery vehicle prevents extensive aggregation of hypericin before injection and assures an efficient transfer to serum lipoproteins upon injection. These results may also be extended to radiolabeled derivatives and other lipophilic photosensitizers, such as porphyrins, phthalocyanines, naphthalocyanines and chlorines, with similar aggregation properties.

Animals↗
PubMed2006

Dual-tracer dopamine transporter and perfusion SPECT in differential diagnosis of parkinsonism using template-based discriminant analysis.

UNLABELLED: Clinical differential diagnosis in parkinsonism can be difficult especially at early stages. We investigated whether combined perfusion and dopamine transporter (DAT) imaging can aid in the differential diagnosis of parkinsonian disorders: idiopathic Parkinson's disease (IPD), progressive supranuclear palsy (PSP), multiple system atrophy (MSA), dementia with Lewy bodies (LBD), and essential tremor (ET). METHODS: One hundred twenty-nine patients were studied, retrospectively (69 males; 24 MSA, 12 PSP, 8 LBD, 27 ET, and 58 IPD; mean disease duration, 3.5 +/- 3.7 y). Diagnosis was based on established clinical criteria after follow-up of 5.5 +/- 3.8 y in a university specialist movement disorders clinic. Group characterization was done using a categoric voxel-based design and, second, a predefined volume-of-interest approach along Brodmann areas (BA) and subcortical structures, including striatal asymmetry and anteroposterior indices. Stepwise forward discriminant analysis was performed with cross-validation (CV) using the leave-one-out technique. RESULTS: Characteristic patterns for perfusion and DAT were found for all pathologies. In the parkinson-plus group, MSA, PSP, and LBD could be discriminated in 100% (+CV) of the cases. When including IPD, discrimination accuracy was 82.4% (99% without CV). 2beta-Carbomethoxy-3beta-(4-iodophenyl)nortropane imaging as a single technique was able to discriminate between ET and neurodegenerative forms with an accuracy of 93.0% (+CV); inclusion of perfusion information augmented this slightly to 97.4% (+CV). CONCLUSION: Dual-tracer DAT and perfusion SPECT in combination with discrimination analysis allows an automated, accurate differentiation between the most common forms of parkinsonism in a clinically relevant setting.

Algorithms↗
PubMed2005

Characterisation and biodistribution of two neutral 99mTc(CO)3 complexes with a tridentate ligand.

N-(2-Mercapto-propyl)-1,2-phenylenediamine (MPPDA) and N-beta-aminoethylglycine (AEG) were labelled with 99mTc(CO)3(+) to form the neutral complexes [99mTc(CO)3(MPPDA)] and [99mTc(CO)3(AEG)]. Both complexes were formed in excellent yields and their identity was confirmed by LC-MS. In mice, none of the new tracer agents showed brain uptake. [(99m)Tc(CO)3(MPPDA)] was trapped mainly in the liver and excreted via the hepatobiliary system, whereas [99mTc(CO)3(AEG)] was excreted rapidly via the kidneys to the urine.

Animals↗
PubMed2005

Synthesis, characterization, and pharmacokinetic evaluation of a potential MRI contrast agent containing two paramagnetic centers with albumin binding affinity.

A dinuclear gadolinium(III) complex of an amphiphilic chelating ligand, containing two diethylenetriamine-N,N,N',N'',N''-pentaacetate (DTPA) moieties bridged by a bisindole derivative with three methoxy groups, has been synthesized and evaluated as a potential magnetic resonance imaging (MRI) contrast agent. Nuclear magnetic relaxation dispersion (NMRD) measurements indicate that at 20 MHz and 37 degrees C the dinuclear gadolinium(III) complex has a much higher relaxivity than [Gd(DTPA)] (6.8 vs 3.9 s(-1) mmol(-1)). The higher relaxivity of the dinuclear gadolinium(III) complex can be related to its reduced motion and larger rotational correlation time relative to [Gd(DTPA)]. In the presence of human serum albumin (HSA) the relaxivity value of the noncovalently bound dinuclear complex increases to 15.2 s(-1) per mmol of Gd3+, due to its relatively strong interaction with this protein. The fitted value of the binding constant to HSA (Ka) was found to be 10(4) M(-1). Because of its interaction with HSA, the dinuclear complex exhibits a longer elimination half-life from the plasma, and a better confinement to the vascular space compared to the commercially available [Gd(DTPA)] contrast agent. Transmetalation of the dinuclear gadolinium(III) complex by zinc(II) has been investigated. Biodistribution studies suggest that the complex is excreted by the renal pathway, and possibly by the hepatobiliary route. In vivo studies indicated that half of the normal dose of the gadolinium(III) complex enhanced the contrast in hepatic tissues around 40 % more effectively than [Gd(DTPA)]. The dinuclear gadolinium(III) complex was tested as a potential necrosis avid contrast agent (NACA), but despite the binding to HSA, it did not exhibit necrosis avidity, implying that binding to albumin is not a key parameter for necrosis-targeting properties.

Animals↗
PubMed2005

Necrosis avid contrast agents: functional similarity versus structural diversity.

Two categories of necrosis-avid contrast agents (NACAs), namely porphyrin- and nonporphyrin-based complexes, have thus far been discovered as necrosis-targeting markers for noninvasive magnetic resonance imaging (MRI) identification of acute myocardial infarction, assessment of tissue or organ viability, and therapeutic evaluation after interventional therapies. In addition to necrosis labeling, other less-specific functions, such as first-pass perfusion, blood pool contrast effect, hepatobiliary contrast enhancement (CE), adrenal and spleen CE, and renal functional imaging, also are demonstrated with NACAs. Despite various investigations with a collection of clues in favor of certain hypotheses, the mechanisms of such a unique targetability for NACAs still remain to be elucidated. However, a few things have become clear that porphyrin-like structures are not necessary for necrosis avidity and the albumin binding is not the supposed driving force but only a parallel nonspecific feature shared by both NACAs and non-NACA substances. Although the research and development of NACAs still remain in preclinical stage at a relatively small scale, their significance rests upon striking enhancement effects, which may warrant their eventual versatile clinical applications. The present review article is intended to summarize the cumulated facts about the evolving research on this topic, to demonstrate experimental observations for better understanding of the mechanisms, to trigger broader public interests and more intensive research activities, and to advocate, toward both academics and industries, further promotion of preclinical and clinical development of this unique and promising class of contrast agents.

Animals↗
PubMed2003

Identity confirmation of 99mTc-MAG3, 99mTc-sestamibi and 99mTc-ECD using radio-LC-MS.

Due to the low concentrations in which 99mTc-radiopharmaceuticals are obtained (4-40 ng/ml), confirmation of the identity of these tracer agents in the European Pharmacopoeia is generally performed only indirectly by assessment of their retention times on RP-HPLC. We have investigated whether it is possible to obtain more direct proof of the identity of technetium-99m labelled radiopharmaceuticals using radio-LC-MS. As representative examples, negatively charged 99mTc-MAG3, positively charged 99mTc-Sestamibi and neutral 99mTc-ECD were used. The three technetium-99m radiopharmaceuticals were prepared in several conditions to obtain variable relative amounts of radiochemical impurities and variable concentrations of the complexes (pico- to nanomolar). The preparations were analyzed on a reversed phase C18 HPLC column using a radio-LC-MS system equipped with a time of flight mass spectrometer with electrospray ionization in positive (99mTc-Sestamibi, 99mTc-ECD) or negative (99mTc-MAG3, 99mTc-ECD) mode. For each of the studied complexes, the main peak in the radiometric channel coincided with the expected molecular ion mass of the corresponding technetium complex in the mass spectrometer channel. The relative error on the measured accurate mass was in the range of 10 ppm. The identity of several radiochemical impurities of the three technetium complexes was also confirmed or established. It is concluded that radio-LC-MS can be a sensitive aid in quality control of 'no carrier added' radiopharmaceuticals.

Chromatography, Liquid↗
PubMed2003

The value of (18)FDG-PET for the detection of infected hip prosthesis.

We compared the accuracy of fluorine-18 labelled 2-fluoro-2-deoxy- d-glucose positron emission tomography ((18)FDG PET) with that of technetium-99m hexamethylpropylene amine oxime leucocyte scintigraphy (LS) in the detection of infected hip prosthesis. Seventeen patients with a hip prosthesis suspected for infection were prospectively included and underwent (99m)Tc-methylene diphosphonate bone scintigraphy (BS), LS and an (18)FDG-PET scan within a 2-week period. Seven volunteers with ten asymptomatic hip prostheses were used as a control group and underwent BS and an (18)FDG-PET scan. Bacteriology of samples obtained by surgery or by needle aspiration and/or clinical follow-up for up to 6 months were used as the gold standard. Planar images of BS and LS (4 and 24 h p.i.) were acquired, followed by single-photon emission tomography (SPET) LS images (after 4 h). These images were scored as positive or negative by two experienced readers. The (18)FDG-PET scans of the patients were compared with the tracer distribution pattern in the asymptomatic control group and with BS. A phantom study was performed in order to identify artefacts. For this purpose, three different attenuation correction methods were tested. The combined analysis of the planar BS and LS resulted in a 75% sensitivity and a 78% specificity. The SPET LS images showed a better lesion contrast, resulting in an 88% sensitivity and a 100% specificity, while 24-h planar images were of no additional value. The analysis of PET images alone resulted in an 88% sensitivity and a 78% specificity. The combination of (18)FDG-PET and BS images resulted in an 88% sensitivity and a 67% specificity. Given the presence of small errors near the edge of the metal, which can induce significant artefacts in the corrected emission image, we decided to use the data without attenuation correction. In this preliminary study, (18)FDG-PET scans alone showed the same sensitivity as combined BS and LS, although the specificity was slightly lower.

Adult↗
PubMed2003

Optimization of the preparation of 99mTc-labeled Hynic-derivatized Annexin V for human use.

Hydrazino nicotinate (Hynic) is one of the most attractive bifunctional agents designed for the labeling of proteins with (99m)Tc. Recently, a (99m)Tc-labeled Hynic-Annexin V derivative has been described and successfully evaluated in animal models of apoptosis. Prior to a phase I human study, the preparation of (99m)Tc-Hynic-Annexin V has been optimized. The influence of the Hynic-load of Annexin V, amount of protein, nature and amount of reducing agent, activity and co-ligand on the labeling yield were evaluated using ITLC and size-exclusion FPLC. Optimal labeling yields were obtained when 60-90 microgram Hynic-Annexin V was labeled with up to 1.11 GBq (30 mCi) (99m)TcO(4)-using 10-20 microgram SnCl(2).2H(2)O as reducing agent and 1.5 mg tricine as the co-ligand. Biodistribution in normal mice was comparable to literature data.

Animals↗
PubMed2003

Accumulation and photocytotoxicity of hypericin and analogs in two- and three-dimensional cultures of transitional cell carcinoma cells.

The aim of this study was to investigate the in vitro cellular accumulation, distribution and photocytotoxic effect of hypericin in two-dimensional (2-D) and three-dimensional (3-D) cultured RT-112 transitional cell carcinoma cells of the bladder. In addition, two iodinated derivatives of hypericin were incorporated to investigate whether these analogs, with their increased lipophilicity and heavy-atom effect, display a different biological behavior and optimized photodynamic effect. The results indicate that hypericin and mono-iodohypericin behave similarly in terms of cellular accumulation, spheroidal distribution and photocytotoxic effect. In contrast, di-iodohypericin concentrated to a higher extent in monolayers and spheroids, but the accumulation was restricted to the outermost part of the spheroid. An inverse correlation therefore seems to exist between the extent of cellular uptake under 2-D conditions and the penetration of the compounds in multicellular systems. Moreover, a less pronounced photocytotoxic effect was observed for di-iodohypericin in both 2-D and 3-D cell culture systems. It can be concluded that iodinated derivatives of hypericin do not show an increased cytotoxic effect upon irradiation in either monolayers or spheroids. Moreover, this study shows that when new photosensitizers are preclinically developed, the use of 3-D cell aggregates is critical for a correct evaluation of their efficacy.

Anthracenes↗
PubMed2002

Intracoronary beta-radiation of de novo coronary lesions using a (186)Re liquid-filled balloon system: six-month results from a clinical feasibility study.

Vascular brachytherapy has shown to be effective for in-stent restenosis, but efficacy in de novo lesions remains uncertain. We evaluated feasibility and outcome of intracoronary beta-radiation therapy in de novo coronary lesions using a (186)Re liquid-filled balloon system. Thirty-three patients received 20 Gy (186)Re beta-radiation immediately after balloon angioplasty. The 6-month restenosis rate was 41% (12/29) and restenosis was located within the target lesion in eight patients and at the edges of the injured and irradiated segment, outside the target lesion, in four patients. At 6 months, four patients (12%), all stented during the initial procedure, had experienced a late (> 30 days) total occlusion. Intracoronary beta-radiation therapy of de novo coronary lesions using (186)Re is technically feasible. No reduction in restenosis was observed. The high incidence of late total occlusions may have been prevented by avoiding new stent implantation and prolonging double antiplatelet therapy.

Aged↗
PubMedDate not supplied

Development of a conjugate of (99m)Tc-EC with aminomethylenediphosphonate in the search for a bone tracer with fast clearance from soft tissue.

For the currently used (99m)Tc-labeled diphosphonates such as (99m)Tc-MDP and (99m)Tc-HDP, the required interval of 2.5 to 3 h between injection and the scintigraphic bone imaging is an inconvenience. The present study was set up in an attempt to develop a technetium-99m-labeled diphosphonate with efficient bone uptake and more rapid clearance from blood and soft tissue by renal extraction and excretion so that it would be possible to start imaging as early as 1 h after injection. A conjugate of the new renal tracer agent (99m)Tc-ethylene dicysteine ((99m)Tc-L,L-EC), covalently bound via one of its carboxylates with aminomethylenediphosphonic acid (AMDP), was synthesized in seven steps. EC-AMDP could be labeled easily and efficiently with (99m)Tc at pH > or = 12 and room temperature. Analysis using ion pair reversed phase high performance liquid chromatography showed the formation of a mixture of two main compounds with reproducible relative ratios, which were stable as a function of time. In a baboon, the scintigraphic images obtained with the new agent showed good quality bone scans, with clear visualization of the skeleton and low soft tissue activity at respectively 1 and 2 h after injection.

Animals↗