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Biomedical subjects

Rudi A Dierckx

Publications and source records attributed to Rudi A Dierckx.

At least 19 recordsLinked to original sources
PubMed2006

123/125I-labelled 2-iodo-L: -phenylalanine and 2-iodo-D: -phenylalanine: comparative uptake in various tumour types and biodistribution in mice.

PURPOSE: In vitro in the R1M cell model and in vivo in the R1M tumour-bearing athymic model, both [(123)I]-2-iodo-L: -phenylalanine and [(123)I]-2-iodo-D: -phenylalanine have shown promising results as tumour diagnostic agents for SPECT. In order to compare these two amino acid analogues and to examine whether the observed characteristics could be generalised, both isomers were evaluated in various tumour models. METHODS: Transport type characterisation in vitro in A549, A2058, C6, C32, Capan2, EF43fgf4, HT29 and R1M cells with [(123)I]-2-iodo-L: -phenylalanine was performed using the method described by Shotwell et al. Subsequently, [(123)I]-2-iodo-L: -phenylalanine and [(123)I]-2-iodo-D: -phenylalanine tumour uptake and biodistribution were evaluated using dynamic planar imaging and/or dissection in A549, A2058, C6, C32, Capan2, EF43fgf4, HT29 and R1M inoculated athymic mice. Two-compartment blood modelling of the imaging results was performed. RESULTS: In vitro testing demonstrated that [(123)I]-2-iodo-L: -phenylalanine was transported in all tumour cell lines by LAT1. In all tumour models, the two amino acid analogues showed the same general biodistribution characteristics: high and specific tumour uptake and renal tracer clearance. Two-compartment modelling revealed that the D: -isomer showed a faster blood clearance together with a faster distribution to the peripheral compartment in comparison with [(123)I]-2-iodo-L: -phenylalanine. CONCLUSION: [(123)I]-2-iodo-L: -phenylalanine and its D: -isomer are promising tumour diagnostic agents for dynamic planar imaging. They showed a high and similar uptake in all tested tumours. [(123)I]-2-iodo-D: -phenylalanine showed better tracer characteristics concerning radiation dose to other organs.

Animals↗
PubMed2006

Prediction of functional recovery after revascularization in patients with chronic ischaemic left ventricular dysfunction: head-to-head comparison between 99mTc-sestamibi/18F-FDG DISA SPECT and 13N-ammonia/ 18F-FDG PET.

PURPOSE: (18)F-FDG PET is an important modality for myocardial viability assessment in patients with left ventricular (LV) dysfunction. Dual-isotope simultaneous acquisition (DISA) SPECT may be an alternative to PET. The aim of this study was to compare the diagnostic performance of PET and DISA SPECT for the prediction of improvement in regional and global LV function as well as LV reverse remodelling after revascularization. METHODS: Patients (n=47) with chronic coronary artery disease and LV dysfunction underwent DISA SPECT (with (99m)Tc-sestamibi and (18)F-FDG) and PET (with (13)N-ammonia and (18)F-FDG) on the same day to assess viability. All patients underwent revascularization and recovery of function was derived from serial magnetic resonance imaging studies. RESULTS: Of 264 revascularized, dysfunctional segments, 143 (54%) improved in function. For prediction of improvement in regional LV function, PET and DISA SPECT had similar sensitivity (90% versus 89%, NS) and specificity (86% versus 86%, NS). For prediction of improvement in global LV function, sensitivity was 83% for DISA SPECT and 86% for PET (p=NS), whereas both modalities had a specificity of 100%. Finally, sensitivity and specificity for the prediction of LV reverse remodelling were also similar for DISA SPECT and PET. CONCLUSION: In patients undergoing revascularization, DISA SPECT and PET predict the improvement in regional and global LV function and LV remodelling equally well post revascularization.

Aged↗
PubMed2006

Synthesis of 99mTc-HYNIC-interleukin-12, a new specific radiopharmaceutical for imaging T lymphocytes.

PURPOSE: Few radiopharmaceuticals have been described for the study of lymphocyte trafficking despite its high clinical relevance. The main difficulty resides in the identification of a suitable highly specific probe to target these cells. Interleukin-12 (IL12) is a heterodimeric cytokine which plays a key role in the development of Th(1) lymphocytes. The aims of the present study were to label IL12 with (99m)Tc, to evaluate its ability to bind to activated T lymphocytes in vitro and to study its biodistribution in normal mice and mice affected by autoimmune colitis. METHODS: IL12 was derivatised with HYNIC-NHS and labelled with( 99m)Tc. An in vitro binding assay was performed on KIT225 cells, an IL12 receptor-positive cell line. (99m)Tc-IL12 biodistribution in normal mice was studied. Targeting experiments were performed in Balb/c mice injected with KIT225 cells and in mice with chemically induced chronic colitis. RESULTS: (99m)Tc-IL12 labelling efficiency ranged between 75% and 85%. Saturation binding analysis revealed a K (d) of 2.09 nM. Results of biodistribution studies showed a predominant hepatic route of excretion. A significant degree of uptake in the spleen and thymus was also observed. In mice injected with KIT225 cells, (99m)Tc-IL12-specific uptake in these cells increased over time. (99m)Tc-IL12 also accumulated significantly in bowel of mice affected by TNBS-induced colitis showing T lymphocyte infiltration at histology, while accumulation in colon from control animals was negligible. CONCLUSION: We conclude that this radiolabelled cytokine is a suitable candidate for specific in vivo imaging of T lymphocytes: a step forward in molecular imaging of immune-mediated processes.

Animals↗
PubMed2006

Comparative biodistribution study of the new tumor tracer [123I]-2-iodo-L-phenylalanine with [123I]-2-iodo-L-tyrosine.

INTRODUCTION: Both A- and l-type amino acid transport are increased in tumor cells relative to normal tissue; these transport systems have been the major focus of the development of amino acid tumor tracers to overcome the limitations of [(18)F]-fluorodeoxyglucose ((18)F-FDG). The newly developed tracer 2-amino-3-(2-[(123)I]iodophenyl)propanoic acid ([(123)I]-2-iodo-l-phenylalanine) showed high and specific tumor uptake, slow renal elimination and low brain uptake. We compared [(123)I]-2-iodo-L-phenylalanine with 2-amino-3-(4-hydroxy-2-[(123)I]iodophenyl)propanoic acid ([(123)I]-2-iodo-L-tyrosine), an L-tyrosine analogue that has recently entered clinical trials. METHODS: [(123)I]-2-iodo-L-phenylalanine and [(123)I]-2-iodo-L-tyrosine were evaluated in rhabdomyosarcoma tumor-bearing athymic mice by means of dynamic planar imaging (DPI) and dissection. A displacement study with L-phenylalanine was performed to prove the specificity of tracer tumor uptake, and kinetic modeling was applied to the DPI results. Moreover, the biodistribution of both tracers was compared with that of (18)F-FDG. RESULTS: Both [(123)I]-2-iodo-L-phenylalanine and [(123)I]-2-iodo-L-tyrosine showed fast, high and specific tumor accumulation with no significant difference. However, [(123)I]-2-iodo-L-phenylalanine was cleared faster from the blood to the bladder in comparison with the tyrosine analogue. Moreover, [(123)I]-2-iodo-L-phenylalanine tumor uptake equilibrated faster with blood. Dissection showed that [(123)I]-2-iodo-L-tyrosine slightly accumulated in the liver, which was not the case for the phenylalanine analogue. In contrast to (18)F-FDG, both tracers showed low uptake in the heart and normal brain tissue, which is advantageous for tumor detection in these organs. CONCLUSIONS: [(123)I]-2-iodo-L-phenylalanine showed more promising characteristics for oncological imaging as compared with [(123)I]-2-iodo-L-tyrosine. The former tracer not only demonstrated faster blood clearance but also showed that the tracer uptake in the tumor reached its equilibrium with the blood pool activity faster, which led to faster and better tumor contrast. Moreover, both tracers could overcome an important limitation of (18)F-FDG-its high normal brain uptake.

Animals↗
PubMed2006

In vitro screening for synergism of high-linear energy transfer 213Bi-radiotherapy with other therapeutic agents for the treatment of B-cell chronic lymphocytic leukemia.

BACKGROUND: External beam radiotherapy and beta-radioimmunotherapy (RIT) are effective treatments for lymphoid malignancies. The development of RIT with alpha-emitters is attractive, owing to the high (LET) nature and short path length of alpha particles allowing for higher tumor cell kill and lower toxicity to healthy tissues. OBJECTIVES: The aim of this study was to assess the response of B-Cell chronic lymphocytic leukemia (B-CLL) cells in vitro after treatment with chemotherapy (cisplatin, fludarabine, doxorubicin, or vincristine) or other pharmaceuticals (colchicine, simvastatin, or cyclosporin A) in combination with (60)Co-gamma or (213)Bi-alpha-irradiation. METHODS: (213)Bi was eluted from a (225)Ac generator. Apoptosis was scored by flow cytometric analysis of the cells stained with Annexin-V and 7 amino actinomycin D. Metabolic activity was assessed by a MTT assay. RESULTS: The response induced by alpha- irradiation is systematically higher than the response induced by gamma-irradiation. The combination of drug treatment with alpha-irradiation induced a systematic, higher response, compared to treatment with drugs alone, even for the highest concentrations used. For all the drugs used in this study, synergism or additivity was demonstrated for the combination of drugs and radiotherapy with a stronger effect for alpha-particles. CONCLUSIONS: The results of this in vitro study highlight a potential benefit of alpha-irradiation in combination with the drugs considered in this study.

Alpha Particles↗
PubMed2006

Comparison of sigma-ligands and metabolic PET tracers for differentiating tumor from inflammation.

UNLABELLED: Novel radiopharmaceuticals for the detection of tumors and their metastases may be of clinical interest if they are more tumor selective than (18)F-FDG. Increased glucose metabolism of inflammatory tissues is the main source of false-positive (18)F-FDG PET findings in oncology. METHODS: We compared the biodistribution of 4 PET tracers (2 sigma-receptor ligands, (11)C-choline, and (11)C-methionine) with previously published biodistribution data of 3'-deoxy-3'-(18)F-fluorothymidine ((18)F-FLT) and of (18)F-FDG in the same animal model. The model consisted of male Wistar rats that bore tumors (C6 rat glioma in the right shoulder) and also had sterile inflammation in the left calf muscle (induced by injection of 0.1 mL of turpentine). Twenty-four hours after turpentine injection, the rats received an intravenous bolus of PET tracer (approximately 30 MBq in the case of (18)F and 74 MBq for (11)C). RESULTS: (18)F-FDG showed the highest tumor-to-muscle ratio of all radiopharmaceuticals (13.2 +/- 3.0, mean +/- SD), followed at a large distance by the sigma-1 ligand (11)C-SA4503 (5.1 +/- 1.7), (18)F-FLT (3.8 +/- 1.3), the non-subtype-selective sigma-ligand (18)F-FE-SA5845 (3.3 +/- 1.5), (11)C-choline (3.1 +/- 0.4), and (11)C-methionine (2.8 +/- 0.3). sigma-Ligands and (18)F-FLT were relatively tumor selective ((18)F-FE-SA5845, greater than 30-fold; (11)C-SA4503 and (18)F-FLT, greater than 10-fold). The tumor selectivity of (11)C-methionine was only slightly better than that of (18)F-FDG. (11)C-Choline showed equal uptake in tumor and inflammation. All tracers were avidly taken up by proliferative tissue (small intestine, bone marrow). High physiologic uptake of some compounds was observed in brain, heart, lung, pancreas, spleen, and salivary gland. CONCLUSION: sigma-Ligands and (18)F-FLT were more tumor selective than (18)F-FDG, (11)C-choline, or (11)C-methionine in our animal model. However, these novel radiopharmaceuticals were less sensitive than were the established oncologic tracers.

Animals↗
PubMed2006

Nitrate administration increases blood flow in dysfunctional but viable myocardium, leading to improved assessment of myocardial viability: A PET study.

UNLABELLED: SPECT with 99mTc-labeled agents is better able to detect viability after nitrate administration. Nitrates induce vasodilation and may increase blood flow to severely hypoperfused but viable myocardium, thereby enhancing tracer delivery and improving the detection of viability. Quantitative data on the changes in blood flow are lacking in SPECT but can be provided by PET. The aim of the present study was to use PET to evaluate whether nitrate administration increases blood flow to chronically dysfunctional but viable myocardium. METHODS: 13N-Ammonia PET was used to quantitatively assess blood flow, and 18F-FDG PET was used as the gold standard to detect viable myocardium. Twenty-five patients with chronic ischemic left ventricular dysfunction underwent 13N-ammonia PET at rest and after nitrate administration. RESULTS: A significant increase in nitrate-enhanced blood flow was observed in viable segments (from 0.55 +/- 0.15 to 0.68 +/- 0.24 mL/min/g, P < 0.05). No statistically significant change in blood flow was observed in nonviable segments (0.60 +/- 0.20 vs. 0.55 +/- 0.18 mL/min/g). A ratio of at least 1.1 for nitrate-enhanced flow to resting flow allowed optimal detection of viable myocardium, yielding a sensitivity of 82% with a specificity of 100%. CONCLUSION: 13N-Ammonia PET showed a significant increase in nitrate-enhanced blood flow in viable myocardium, whereas blood flow remained unchanged after nitrate administration in nonviable myocardium. Nitrate use during myocardial perfusion imaging will lead to improved assessment of myocardial viability.

Aged↗
PubMed2006

Early response of sigma-receptor ligands and metabolic PET tracers to 3 forms of chemotherapy: an in vitro study in glioma cells.

UNLABELLED: The significant presence of nontumor cell populations within tumors can complicate the assessment of in vivo tumor metabolism during therapy. To more clearly define the impact of cytotoxic agents, we compared early changes in the uptake of 6 PET tracers in cultured glioma cells. Doxorubicin (1 micromol/L), cisplatin (10 micromol/L), and 5-fluorouracil (10 mmol/L) were selected to target different aspects of cellular metabolism. METHODS: The tracers were 2 extracellular sigma-receptor ligands, (18)F-FE-SA5845 (nonsubtype selective) and (11)C-SA4503 (sigma-1), the nucleoside 3'-deoxy-3'-(18)F-fluorothymidine ((18)F-FLT), (11)C-choline, (11)C-methionine, and (18)F-FDG. C6 glioma cells were grown as monolayers and exposed to cytotoxic agents at concentrations at least 1 order of magnitude higher than the concentration for 50% growth inhibition of this cell line. Effects on cellular parameters were measured after 0, 1, 2, 3, 4, and 24 h. RESULTS: All treatments resulted in a decline in cell numbers within 24 h. The binding of the sigma-ligands (11)C-SA4503 and (18)F-FE-SA5845 and the uptake of (11)C-choline (normalized for the number of viable cells) were strongly increased. The uptake of (18)F-FDG showed little change, and cellular accumulation of (18)F-FLT and (11)C-methionine was decreased. Uptake of (18)F-FLT and (11)C-methionine was related to the fraction of cells in S-phase, but not under all conditions: (a) doxorubicin caused a more rapid decline in (18)F-FLT uptake than in the S-phase fraction because of depletion of cellular adenosine triphosphate, and (b) cisplatin inhibited the transport of (11)C-methionine across the tumor cell membrane. CONCLUSION: Increased binding of sigma-ligands and an increased uptake of (11)C-choline after chemotherapy may reflect active membrane repair in damaged cells. (18)F-FLT and (11)C-methionine behaved as proliferation markers. However, the accumulation of (18)F-FDG reflected not the proliferation rate but, rather, the number of viable cells per well.

Animals↗
PubMed2005

Maturation of malfunctioning kidneys.

Because loss of functional renal mass is compensated by hyperfiltration of remaining tissue, one could hypothesize that a damaged kidney might not have the same rate of maturation as the contralateral one. To verify this, maturation was evaluated in children with asymmetrical renal function during early life. Twenty-five children were selected having had 2 (99m)Tc-MAG3 renograms combined with (51)Cr-EDTA clearance measurement, enabling estimation of glomerular filtration rate (GFR), split renal function (SRF), and single kidney GFR (SKGFR). The first test had to be performed before the age of 18 months and SRF on the affected side had to be < or =40%. Moreover, GFR had to increase between the 2 tests by > or =10 mL(-1) min/1.73 m(2), reflecting maturation due to age. For 18 children SRF changed by between -5% and +5%. For 4 children an increase of > or =5% was observed whereas for the remaining 3 a decrease of > or =5% occurred. For the first 22 kidneys, mean increase of SKGFR was +6.3 mL(-1) min/1.73 m(2)(SD: 6). For the 3 kidneys with > or =5% SRF decrease, SKGFR remained unchanged in 2 (+0.3 and -3 mL min(-1)/1.73 m(2)) and increased in the third patient (+15 mL min(-1)/1.73 m(2)). In conclusion, renal maturation is comparable in both the malfunctioning kidney and the contralateral normal functioning side.

Child↗
PubMed2005

In vivo evaluation of [123I]-4-iodo-N-(4-(4-(2-methoxyphenyl)-piperazin-1-yl)butyl)-benzamide: a potential sigma receptor ligand for SPECT studies.

In this study, in vivo evaluation in mice and rabbits of [123I]-4-iodo-N-(4-(4-(2-methoxyphenyl)-piperazin-1-yl)butyl)-benzamide ([123I]-BPB), a potential radioligand for visualisation of the sigma receptor by single photon emission computed tomography (SPECT), is reported. The compound possesses appropriate lipophilicity (log P=2.2) and binds sigma-1 and sigma-2 receptors (pKi=6.51 and 6.79, respectively). In mice, this new radioiodinated tracer exhibited high brain uptake (4.99% ID/g tissue at 10 min postinjection) and saturable binding (3.06% ID/g tissue at 10 min postinjection) as determined by pretreatment with unlabeled [123I]-BPB. A metabolite study demonstrated no (less than 5%) labeled metabolites in the brain. In rabbits, regional brain distribution was investigated and the tracer displayed high, homogeneous central nervous system uptake. Selectivity was assessed by competition experiments with known sigma ligands. Metabolite analysis showed no (less than 8%) labeled metabolites in the rabbit brain. In conclusion, our findings indicate that [123I]-BPB is not a suitable tracer for visualisation of D3 receptors while its potential for sigma receptor imaging is severely hampered by its affinity for dopamine receptors.

Animals↗
PubMed2005

In vivo apoptosis detection with radioiodinated Annexin V in LoVo tumour-bearing mice following Tipifarnib (Zarnestra, R115777) farnesyltransferase inhibitor therapy.

In this paper, the use of (123)I-Annexin V for the detection of farnesyltransferase inhibitor (FTI)-induced apoptosis in tumour-bearing athymic mice is described. In vitro binding assays on LoVo cells show time- and dosage-dependent (125)I-Annexin V binding upon treatment with Tipifarnib (Zarnestra, R115777), a selective and potent FTI. In vivo experiments using planar gamma scintigraphy on LoVo inoculated mice show a 40% increased (123)I-Annexin V uptake 8 h after a single oral administration of 100 mg/kg Tipifarnib in 20% beta-cyclodextrin in 0.1 M HCl, as well as after 3 days of twice daily treatments with the same dose. Ex vivo TUNEL assays, detecting end-stage apoptotic cells, correlate significantly with both in vitro and in vivo results. The percentage of necrosis is also increased by Tipifarnib treatment, but is too low to interfere with the (123)I-Annexin V uptake. It can be concluded that (123)I-Annexin V can be used to monitor Tipifarnib-induced apoptosis in LoVo xenograft tumours in athymic mice. Future applications might include the early prediction of FTI response and the selection of FTI-sensitive patients very shortly after treatment initiation. Subsequently, such patients would greatly benefit from a noninvasive and fast therapy evaluation.

Adenocarcinoma↗
PubMed2005

Detailed spatio-temporal solids concentration profiling during batch settling of activated sludge using a radiotracer.

In building and tuning good settling models for secondary clarifiers of wastewater treatment plants, there is a need for measured continuous solids concentration profiles during batch settling. Conventional measuring techniques have difficulties in recording this kind of data, either because they are invasive, or because of the low solids concentration and/or solids density of activated sludge. This paper investigates a novel non-invasive measurement technique borrowed from nuclear medicine, using a solids radiotracer and gamma cameras, to obtain solids concentration profiles during the batch settling of activated sludge, in a pilot-scale column with a height of 1m. The technique does not disturb the settling process, does not alter the settling characteristics, gives profiles every minute and every few millimeters, and is capable of measuring in a range of 0-25 g/l with high accuracy. Dynamic solids concentration profile measurements were performed for sludges of different wastewater treatment plants, and at different initial concentrations. The results show a quantitative representation of the settling process, and reveal hindered and compression settling.

Gamma Cameras↗
PubMed2005

Impact of waiting on the perception of service quality in nuclear medicine.

BACKGROUND: This is the first study examining the link between waiting and various dimensions of perceived service quality in nuclear medicine. METHODS: We tested the impact of selected waiting experience variables on the evaluation of service quality, measured using the Servqual tool, of 406 patients in nuclear medicine, with objective and subjective waiting times as co-variates. The sequence of events in service delivery in nuclear medicine (waiting time before injection, waiting time before scanning and total waiting time) is taken into account. RESULTS: Patients underestimated the waiting time before injection and the total waiting time, while overestimated the waiting time before scanning. Our results show that the total subjective waiting time has more impact on the reliability dimension (R2(adj)=0.148) than on the other service quality dimensions of Servqual. Providing information about the reasons for delay had a significant main effect on the perception of reliability (F=9.64, P=0.02). CONCLUSIONS: The study stresses the importance of explaining the causes for delay to increase patients' perceptions of reliability of the nuclear medicine department and contains several findings that should assist service managers to formulate more effective waiting perception strategies.

Adolescent↗
PubMed2005

Good clinical practice: historical background and key aspects.

Clinical research trials (both academic and industry sponsored) are increasingly playing a role in various medical disciplines, including younger fields of clinical trial interest, such as nuclear medicine research. Knowledge for and compliance with good clinical practice (GCP) is essential for anyone involved. In this review article, key aspects of GCP and the responsibilities of investigators, monitors and sponsors are described. In addition, a comprehensive overview of the historical background on the development of GCP from the US Pure Food and Drugs Act of 1906 over the Nuremberg Code, the Kefauver-Harris Amendments and the Declaration of Helsinki until now is given. Knowledge of the historical background may help understand the developments in GCP.

Clinical Trials as Topic↗
PubMed2005

The good laboratory practice and good clinical practice requirements for the production of radiopharmaceuticals in clinical research.

Radiopharmaceuticals account for more than 95% of the group of sterile pharmaceutical products and should therefore be handled and produced with care. Since the introduction of the European directive, all pharmaceuticals used in clinical studies must be prepared under good manufacturing practice (GMP) conditions. This review aims to give an overview of the basic principles and guidelines for the preparation of radiopharmaceuticals. Special attention is given to the production area environment and personnel, the two basic requirements for GMP productions. Especially for the production area, two philosophies have to be combined: the cascade system of over-pressure for the production of pharmaceuticals and the under pressure system for the manufacturing of radioisotopes. Personnel should be selected based on education and regularly given special training for the handling of radioactive material. Compared to pharmaceuticals, radiopharmaceuticals have their own labels, taking into account their specific nature. Besides the standard quality control, other items for quality control of radiopharmaceuticals are also discussed in this article.

Biomedical Research↗
PubMed2005

The feasibility of repeated left ventricular ejection fraction analysis with sequential single-dose radionuclide ventriculography.

OBJECTIVE: Repeated left ventricular ejection fraction (LVEF) analyses with sequential single-dose radionuclide ventriculography might be an interesting technique for monitoring the effect of positive inotropic interventions. The aim of the study was to assess the reproducibility of LVEF measurement with planar radionuclide ventriculography within 3 h, using a standard single dose of radioactive tracer. METHODS: Sixteen patients underwent routine planar radionuclide ventriculography with a standard dose of 500 MBq of [Tc]pertechnetate and returned after 3 h for a repeat planar radionuclide ventriculography without administration of additional tracer. RESULTS: The average initial LVEF was 35.1+/-18.6%-point (range, 12%-point to 68%-point). The mean difference of the LVEF between the initial planar radionuclide ventriculography and the repeat planar radionuclide ventriculography was 2.8%+/-6.3% (range, -11.8% to 13.3%, P=NS). The correlation between both measurements was significant with a correlation coefficient of 0.995 (P<0.01). Bland-Altman analysis revealed a mean LVEF difference of 0.94%-point between the baseline planar radionuclide ventriculography and the repeat planar radionuclide ventriculography (95% confidence interval: -2.7%-point to 4.5%-point). The visual wall motion assessment showed excellent reproducibility, with a kappa-statistic of 0.98. CONCLUSION: Repeated radionuclide ventriculography with a 3 h interval using a single standard dose of 500 MBq of [Tc]pertechnetate is highly reproducible and will be useful for monitoring the effect of positive inotropic interventions.

Feasibility Studies↗