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Biomedical subjects

R A Dierckx

Publications and source records attributed to R A Dierckx.

At least 55 records · Page 3Linked to original sources
PubMed2001

Patient dosimetry after 131I-MIBG therapy for neuroblastoma and carcinoid tumours.

AIM: The aim of the study was to determine the equivalent total body dose (ETBD) using the cytokinesis-blocked micronucleus assay in 22 131 I-meta-iodobenzylguanidine (131 I-MIBG) therapies (18 neuroblastoma, mean 5097 MBq, SD 1591; and four carcinoid tumours, mean 7681 MBq, SD 487). The results are correlated with the total body radiation dose according to the Medical Internal Radiation Dosimetry (MIRD) formalism. METHODS: For each patient, blood samples were taken immediately before and 1 week after 131I-MIBG therapy. The first blood sample was irradiated in vitro with 60Co gamma-rays to determine the dose-response curve. Micronuclei were scored in 1000 binucleated cells. By using the dose-response curve the ETBD was derived from the increase in micronuclei after 131I-MIBG therapy (second blood sample). Based on three consecutive biplanar scans taken at 3, 6 and 9 days post-administration respectively, the total body dose following the MIRD formalism was calculated. RESULTS: The micronucleus assay was evaluable in only 14 out of 22 131I-MIBG therapies due to cell division inhibition caused by previous chemotherapy treatments and lymphocyte dilution due to blood transfusions given shortly after 131I-MIBG therapy. For these 14 therapies, the mean micronucleus yield after 131I-MIBG therapy was significantly increased (P < 0.01) with a mean of 92 (SD 77) for neuroblastoma patients and with a mean of 35 (SD 8) for carcinoid patients. The increase observed in the present study is greater than previously observed after 131I therapy and 89Sr therapy but much lower than after external beam radiotherapy. For all patients treated with multiple therapies, the initial increase in micronucleus yield had at least partially recovered by the time of the next therapy. This might be explained by an increased turnover of lymphocytes. A mean ETBD of 0.95 Gy (SD 0.55) for neuroblastoma patients and a mean of 0.46 Gy (SD 0.09) for carcinoid patients was calculated. A reasonable correlation (R = 0.87) between the ETBD and the MIRD dose was obtained. The slope value of 0.75 can be explained by the low dose rate effect. CONCLUSIONS: The observation in the present study of important inter-individual variability in the total body dose, with the possibility of high dose values, suggests the necessity of individual dosimetry when administering 131I-MIBG therapy, especially considering that generally more than one therapy is given to each patient.

3-Iodobenzylguanidine↗
PubMed2001

57Co SPECT, 99mTc-ECD SPECT, MRI and neuropsychological testing in senile dementia of the Alzheimer type.

Inflammatory mechanisms contribute to the pathophysiology of senile dementia of the Alzheimer type (sDAT). Previous studies have shown that 57Co single photon emission computed tomography (SPECT) is able to visualize inflammatory lesions, probably by means of the final common pathway of Ca2+ homeostasis disturbance in both neuronal degeneration and inflammation. The aims of this study were: (1) to detect 57Co SPECT changes in sDAT patients; (2) to correlate these findings with those of conventional neuroimaging techniques and neuropsychological testing (NPT); and (3) to compare 57Co SPECT findings in sDAT patients with those in other types of dementia. Six patients suffering from probable sDAT were included and compared with four patients suffering from other types of dementia. All patients had a magnetic resonance imaging (MRI) scan, NPT, 57Co and 99mTc-ethyl cysteinate dimer (ECD) SPECT scan. Perfusion SPECT images were semiquantitatively evaluated by comparison with an age-matched normal database, while 57Co SPECT scans were assessed qualitatively. MRI and 99mTc-ECD SPECT scans yielded conclusive results with regard to the exclusion of other pathologies and the confirmation of the diagnosis. Using visual analysis, 57Co SPECT scans were unable to show any regional raised uptake, irrespective of the disorder, depth or extent of the perfusion defects, presence of atrophy on MRI or the results of NPT.

Aged↗
PubMed2001

Brain perfusion SPECT: age- and sex-related effects correlated with voxel-based morphometric findings in healthy adults.

PURPOSE: To investigate brain perfusion at single photon emission computed tomography (SPECT) as a function of age and sex in healthy adult volunteers and to correlate perfusion with gray matter concentration determined by using voxel-based morphometry (VBM). MATERIALS AND METHODS: Eighty-one healthy volunteers underwent both technetium 99m ethylene cysteine dimer SPECT and three-dimensional magnetization preparation rapid acquisition gradient-echo magnetic resonance (MR) imaging. Statistical parametric mapping was used to conduct VBM analysis of the morphologic data, which were compared voxel by voxel with the results of a similar analysis of the perfusion data and more specifically in brain areas showing significant perfusion changes. RESULTS: VBM data, as compared with perfusion changes, indicated a more symmetric age-related gray matter volume decrease along the Sylvian fissure and in subcortical regions (P < .001). The combination of functional and structural changes indicated a relatively lower functional decrease with aging, as compared with the structural atrophy in the visual, parietal, sensorimotor, and right prefrontal cortices. Significant relative morphologic sex-based differences were found in the cerebellar and temporal cortices, but the comparison did not reveal significant differences between the functional and morphometric data. CONCLUSION: Age-related perfusion changes are paralleled by similar more symmetric changes in gray matter concentration, which are more prominent than the perfusion changes in some regions. No sex-based differences between perfusion and gray matter concentration were found.

Adult↗
PubMed2001

Fluorine-18 fluorodeoxyglucose-position emission tomography: a highly accurate imaging modality for the diagnosis of chronic musculoskeletal infections.

BACKGROUND: The noninvasive diagnosis of chronic musculoskeletal infections remains a challenge. Recent studies have indicated that fluorine-18 fluorodeoxyglucose-positron emission tomography is a highly accurate imaging technique and is significantly more accurate than the combination of a bone scan and a white blood-cell scan for the diagnosis of chronic infection in the central skeleton (p < 0.05). However, patients who had had surgery within the previous two years were excluded from study. It was our aim to evaluate the technique in an unselected, clinically representative population. METHODS: Sixty patients with a suspected chronic musculoskeletal infection involving the central skeleton (thirty-three patients) or the peripheral skeleton (twenty-seven patients) were studied with fluorine-18 fluorodeoxyglucose-positron emission tomography. Thirty-five patients had had surgery within the previous two years. The fluorine-18 fluorodeoxyglucose-positron emission tomography studies were read in a blinded, independent manner by two experienced readers. The final diagnosis was based on histopathological studies or microbiological culture (eighteen patients) or on clinical findings after at least six months of follow-up (forty-two patients). RESULTS: On the final composite assessment, twenty-five patients had infection and thirty-five did not. All twenty-five infections were correctly identified by both readers. There were four false-positive findings; in two of these cases, surgery had been performed less than six months prior to the study. The sensitivity, specificity, and accuracy were 100%, 88%, and 93% for the whole group; 100%, 90%, and 94% for the subgroup of patients with a suspected infection of the central skeleton; and 100%, 86%, and 93% for the subgroup of patients with a suspected infection of the peripheral skeleton. Interobserver agreement was excellent (kappa = 0.97). CONCLUSIONS: Fluorine-18 fluorodeoxyglucose-positron emission tomography is highly accurate as a single technique for the evaluation of chronic musculoskeletal infections. It is especially valuable in the evaluation of the central skeleton, where white blood-cell scans are less useful. Because of its simplicity and high degree of accuracy, it has the potential to become a standard technique for the diagnosis of chronic musculoskeletal infections. Further studies are needed to assess its ability to identify infections at the sites of total joint replacements and to distinguish infection from aseptic loosening of these prostheses.

Adolescent↗
PubMed2001

Biodistribution and dosimetry of (99m)Tc-RP527, a gastrin-releasing peptide (GRP) agonist for the visualization of GRP receptor-expressing malignancies.

UNLABELLED: The aim of this study was to determine the human biodistribution and radiation dosimetry of (99m)Tc-RP527, a promising radioligand for the visualization of gastrin-releasing peptide (GRP) receptor-expressing human malignancies. METHODS: Whole-body scans were obtained up to 48 h after intravenous injection of 555 MBq (99m)Tc-RP527 in each of 6 subjects. Blood samples were taken at various times up to 48 h after injection. Urine was collected up to 48 h after injection for calculation of renal clearance and whole-body clearance. Time-activity curves were generated for the thyroid, heart, breasts in women, testes in men, and liver by fitting the organ-specific geometric mean counts, obtained from regions of interest, on the respective images as a function of the time after injection. The MIRD formulation was applied to calculate the absorbed radiation dose for various organs. RESULTS: The serial whole-body images showed rapid hepatobiliary excretion, resulting in low background and potentially high-contrast imaging of the thoracic region. Imaging of abdominal tumors may prove problematic, however, because of the extensive bowel activity. (99m)Tc-RP527 was predominantly cleared by the kidneys and to a lesser extent by the gastrointestinal tract. The mean excretion in the urine (+/-SD) at 48 h after injection was 58.3 +/- 5.4 percentage of the injected activity corrected for decay to the time of injection. The highest absorbed doses were received by the excretory organs (i.e., the urinary bladder and gallbladder wall). The average effective dose of (99m)Tc-RP527 was estimated to be 0.0095 mSv/MBq. CONCLUSION: The biodistribution of (99m)Tc-RP527 revealed low lung, myocardial, and liver uptake, which allowed early imaging of the supradiaphragmatic region with a favorable dosimetry (including effective dose) for administered activities required for SPECT imaging.

Adult↗
PubMed2001

Iodine-labeled tamoxifen uptake in primary human breast carcinoma.

UNLABELLED: Assessing tumor uptake and retention of (123)I-labeled tamoxifen (TX) could increase our understanding of TX's action and the mechanisms involved in resistance to the drug. METHODS: Nine untreated primary breast carcinoma patients underwent whole-body planar and tomographic (SPECT) imaging 30 min and 4-5 h after injection of 185 MBq (123)I-TX. Tumor-to-normal tissue uptake ratios (T/N) derived from SPECT images were related to estrogen receptor (ER) and progesterone receptor (PR) status. RESULTS: In 4 of 9 patients, all of whom were ER+/PR+, (123)I-TX tumor uptake was clearly depicted. In 2 of them, involved axillary lymph nodes were also visualized. T/N consistently increased over time. All ER+/PR- and ER-/PR- tumors as well as 2 ER+/PR+ tumors were (123)I-TX-. CONCLUSION: These preliminary findings suggest that (123)I-TX is preferentially taken up in alpha-ER+/PR+ breast tumors known to be more likely to respond to endocrine treatment.

Breast Neoplasms↗
PubMed2000

Assessing the performance of SPM analyses of spect neuroactivation studies. Statistical Parametric Mapping.

Several simulations of SPECT neuroactivation studies have been performed in order to determine the influence of both study size and activation focus characteristics on the detection of brain activation foci following a pixel-based statistical analysis. This was achieved by developing a methodology based on the Hoffman software brain phantom, SPECT acquisition simulation software, standard reconstruction software, and the Statistical Parametric Mapping (SPM96) package. We present results on the minimal activation levels required for focus detection. Furthermore, the improved sensitivity of the analysis resulting from the use of an iterative reconstruction technique (OSEM) with regard to the classical filtered backprojection (FBP) is assessed quantitatively, and the various physical, processing, and physiological parameters that potentially influence the detection of foci are discussed. Finally, the influence is investigated of the height threshold as implemented in SPM96 upon the size of the detected foci. Practical guidelines are proposed with regard to the number of subjects per group for SPECT activation studies following the split-dose design.

Brain↗
PubMed2000

Infarct size and recurrence of ventricular arrhythmias after defibrillator implantation.

Infarct size as determined by perfusion imaging is an independent predictor of mortality after implantable cardioverter defibrillator (ICD) implantation in patients with coronary artery disease (CAD) and life-threatening ventricular arrhythmias (VA). However, its value as a predictor of VA recurrence and hospitalisation after ICD implantation is unknown. Therefore, the objective of this study was to evaluate whether infarct size as determined by perfusion imaging can help to identify patients who are at high risk for recurrence of VA and hospitalisation after ICD implantation. We studied 56 patients with CAD and life-threatening VA. Before ICD implantation, all patients underwent a uniform study protocol including a thallium-201 stress-redistribution perfusion study. A defect score as a measurement of infarct size was calculated using a 17-segment 5-point scoring system. Study endpoints during follow-up were documented episodes of appropriate anti-tachycardia pacing and/or shocks for VA and cardiac hospitalisation for electrical storm (defined as three or more appropriate ICD interventions within 24 h), heart failure or angina. After a mean follow-up of 470+/-308 days, 22 patients (39%) had recurrences of VA. In univariate analysis, predictors for recurrence were: (a) ventricular tachycardia (VT) as the initial presenting arrhythmia (86% vs 59% for patients without ICD therapy, P=0.04), (b) treatment with beta-blockers (36% vs 68%, P=0.03) and (c) a defect score (DS) > or = 20 (64% vs 32%, P=0.03). In multivariate analysis, VT as the presenting arrhythmia (chi2=5.51, P=0.02) and a DS > or = 20 (chi2=4.22, P=0.04) remained independent predictors. Cardiac hospitalisation was more frequent in patients with a DS > or = 20 (44% vs 13% for patients with DS < 20, P=0.015) and this was particularly due to more frequent hospitalisations for electrical storm (24% vs 3% for patients with DS < 20, P=0.037). The extent of scarring determined by perfusion imaging can separate patients with CAD into high- and low-risk groups for recurrence of VA and cardiac hospitalisation after ICD implantation.

Adrenergic beta-Antagonists↗
PubMed2000

Biodistribution and dosimetry of [123I]iodo-PK 11195: a potential agent for SPET imaging of the peripheral benzodiazepine receptor.

The highest concentrations of the peripheral benzodiazepine receptor (PBR) are found in the kidneys and heart. In addition, the PBR has been reported to reflect neuro-inflammatory damage by co-localisation with activated microglia. PK 11195 is a high-affinity ligand for the PBR. The aim of this study was to investigate in humans the biodistribution and dosimetry of [123I]iodoPK 11195, a potential single-photon emission tomography tracer for the PBR. Five healthy volunteers were injected with 112 MBq of [123I]iodo-PK 11195. Sequential whole-body scans were performed up to 72 h post injection. Multiple blood samples were taken, and urine was collected to measure the fraction voided by the renal system. Decay-corrected regions of interest of the whole-body images were analysed, and geometric mean count rates were used to determine organ activity. Organ absorbed doses and effective dose were calculated using the MIRD method. [123I]iodo-PK 11195 was rapidly cleared from the blood, mainly by the hepatobiliary system. Approximately 22% was voided in urine after 48 h. Average organ residence times were 0.74, 0.44 and 0.29 h for the liver, upper large intestine and lower large intestine, respectively. The testes received the highest dose, 109.4 microGy/MBq. All other organs investigated received doses of less than 50 microGy/MBq. The effective dose was 40.3 microSv/MBq. In conclusion, [123I]iodo-PK 11195 is a suitable agent for the visualisation of the PBR and indirectly for the imaging of neuro-inflammatory lesions. Taking into account the radiation burden of 7.46 mSv following an administration of 185 MBq, a [123I]iodo-PK 11195 investigation has to be considered an ICRP risk category IIb investigation.

Adult↗
PubMed2000

Radiolabeled estradiol derivatives to predict response to hormonal treatment in breast cancer: a review.

Several radiolabeled steroidal and nonsteroidal estradiol derivatives of which the tumoral uptake is believed to relate quantitatively to the content and binding characteristics of the alpha-estrogen receptor (alphaER) receptor in the target tissue have been synthesized and their imaging potential and clinical usefulness evaluated in vivo in humans. Due to the use of different methodologies and cut-off values for the measurement of alphaER positivity, the use of both quantitative positron emission tomography and semiquantitative single-photon emission tomography, and the difference in patient populations studied, direct comparison of these data is not possible. Individual data, however, fail to substantiate a direct relationship between these radiolabeled estradiol derivatives and alphaER status, in keeping with recent pathophysiological findings demonstrating (1) estradiol sequestration and retention through other than alphaER-mediated, either membrane- or non-membrane-related, mechanisms and (2) an inverse relationship between estradiol uptake and local biosynthesis through aromatization and interconversion in alphaER-positive tumors. Additionally, given the discovery of very high affinity alphaER-like binding sites (Kd, dissociation constant, <0.1 nM), and the potential for underestimation of aER Kd when using ligand binding assays, at least part of the radiolabeled estradiol derivative uptake reflects tumoral perfusion rather than the ligand-receptor binding process. However, the reduction in cellular uptake, membrane sequestration and local biosynthesis of estradiol following tamoxifen treatment in alphaER-responsive tumors should allow early prediction of response to therapy through rapid sequential radiolabeled estradiol scintigraphy with higher accuracy than conventional alphaER estimations, as supported by recent data.

Binding Sites↗
PubMed2000

Technetium-99m RP527, a GRP analogue for visualisation of GRP receptor-expressing malignancies: a feasibility study.

Gastrin-releasing peptide (GRP) receptor scintigraphy could allow prediction of response to GRP receptor-targeted treatment options, early non-invasive diagnosis and in vivo prognostic stratification of GRP receptor-positive tumours. This study reports on the imaging characteristics and efficacy for tumour detection of technetium-99m RP527, a 99mTc chelated targeting peptide derived from bombesin, which binds GRP receptors with high affinity. Ten patients (four men and six women, mean age 56.4 years) either suffering from metastasised prostate (n, number of patients = 4) or breast carcinoma (n=1) or presenting with a clinical diagnosis highly suggestive for breast carcinoma (n=5) were included in the study. In the latter five patients, 99mTc-RP527 scintigraphy was performed prior to diagnostic, e.g. biopsy, and staging examinations. Final diagnosis in these patients was breast carcinoma in all five. In all patients, whole-body planar scans and tomographic images were acquired 1 h and 5-6 h post injection of 555 MBq 99mTc-RP527 and tumour to normal tissue (T/N) ratios determined. 99mTc-RP527 showed specific uptake in four of six breast and one of four prostate carcinomas. T/N ratios derived from planar and tomographic images increased significantly (P<0.01) from 1.65 (SD 1.53) and 3.35 (SD 3.04) to 2.58 (SD 1.26) and 7.23 (SD 8.46), respectively. T/N ratios derived from tomographic images were consistently higher (P<0.01). The data presented suggest that 99mTc-RP527 results in specific tumour localisation and exhibits good imaging characteristics with a good T/N ratio that may be further enhanced by single-photon emission tomography.

Adult↗
PubMed2000

Pharmacological evaluation of [11C]donepezil as a tracer for visualization of acetylcholinesterase by PET.

Donepezil is a highly potent and selective reversible achetylcholinesterase inhibitor. [(11)C]Donepezil is prepared by methylation with [(11)C]CH(3)I of the corresponding 6'-O-desmethylprecursor. Tissue distribution in mice revealed a high uptake in brain and rapid clearance from the blood. Metabolization studies in mice indicated the formation of one (11)C-labeled polar metabolite that didn't penetrate the blood-brain barrier. Regional brain distribution in rabbits didn't reflect the measured achetylcholinesterase distribution in rabbit brain.

Acetylcholinesterase↗
PubMed2000

Adaptive response in patients treated with 131I.

UNLABELLED: The aim of this study was to investigate whether an adaptive response (defined as the induction of radiation tolerance after a small dose of radiation) could be observed in peripheral blood lymphocytes of patients treated with 1311 for thyroid disease. METHODS: For each patient, blood samples were taken immediately before and 1 wk after 131I administration. Each blood sample was divided into 3 fractions and the fractions were subsequently irradiated in vitro with 0, 0.5, and 1.0 Gy 60Co gamma-rays. After blood culture for 70 h, cells were harvested and stained with Romanowsky-Giemsa and micronuclei were counted in 1000 binucleated cells. The increase in micronuclei by the in vitro irradiation of the blood samples taken before and after therapy was compared. In this setup, an adaptive response is represented by a significant decrease of the in vitro induced micronucleus yield after therapy compared with that before therapy. The iodine therapy can be considered as an in vivo adaptation dose, after which the subsequent in vitro irradiation acts as a challenge dose. To investigate the reproducibility of the method, 2 subsequent blood samples of healthy volunteers were taken 7 d apart. Irradiation and cell culture were performed as described. RESULTS: In 8 of 20 patients, a significant (P = 0.0002) decrease was found in the in vitro induced micronucleus yield in the blood sample taken 1 wk after 1311 administration compared with that of the blood sample taken before therapy. No significant (P > 0.1) differences were observed between these 8 patients and the other patients when the number of micronuclei induced in vivo by the iodine treatment and the resulting equivalent total body dose were compared. None of the control subjects showed a significant change in micronucleus yield after in vitro irradiation between both blood samples taken 1 wk apart. CONCLUSION: The iodine treatment can act as an in vivo adaptation dose and can induce an adaptive response that is observed by a decrease of the cytogenetic damage in peripheral blood lymphocytes after in vitro irradiation as a challenge dose. A large interindividual difference was observed.

Adaptation, Physiological↗
PubMed2000

Accurate differentiation of parkinsonism and essential tremor using visual assessment of [123I]-FP-CIT SPECT imaging: the [123I]-FP-CIT study group.

OBJECTIVE: To evaluate whether visual assessment of [123I]-FP-CIT (DaTSCAN, Nycomed Amersham, plc) single photon emission computerized tomography (SPECT) images can differentiate between parkinsonism and essential tremor (ET). METHODS: [123I]-FP-CIT SPECT imaging was conducted in a six-center study of 158 patients with a clinical diagnosis of parkinsonism compared with 27 ET cases and 35 healthy volunteers. Striatal uptake of the radioligand was graded normal or abnormal, and abnormal images were further graded to three levels of severity. An institutional read whereby each center visually assessed the images blinded to the clinical data and a consensus blinded read by a panel of five was undertaken. RESULTS: The institutional reading scored 154 of 158 cases of parkinsonism abnormal, all 27 cases of ET as normal, and 34 of 35 healthy volunteers as normal compared with the consensus blinded read scoring 150 cases of parkinsonism as abnormal, 25 ET cases as normal, and 33 healthy volunteers as normal. Sensitivity for the clinical diagnosis of parkinsonism was 97% and specificity for ET was 100% for the institutional read, whereas sensitivity was 95% and specificity 93% for the consensus blinded read. Semiquantitative analysis of specific: nonspecific caudate and putamen uptake were consistent with the results of visual inspection. CONCLUSION: Visual assessment of [123I]-FP-CIT SPECT images is an easily applied diagnostic test which is helpful in the differential diagnosis of tremor disorders and in confirming a clinical diagnosis of a hypokinetic-rigid syndrome.

Adult↗