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J van den Hoff

Publications and source records attributed to J van den Hoff.

At least 19 recordsLinked to original sources
PubMed2005

Catabolism of native and oxidized low density lipoproteins: in vivo insights from small animal positron emission tomography studies.

The human organism is exposed to numerous processes that generate reactive oxygen species (ROS). ROS may directly or indirectly cause oxidative modification and damage of proteins. Protein oxidation is regarded as a crucial event in the pathogenesis of various diseases ranging from rheumatoid arthritis to Alzheimer's disease and atherosclerosis. As a representative example, oxidation of low density lipoprotein (LDL) is regarded as a crucial event in atherogenesis. Data concerning the role of circulating oxidized LDL (oxLDL) in the development and outcome of diseases are scarce. One reason for this is the shortage of methods for direct assessment of the metabolic fate of circulating oxLDL in vivo. We present an improved methodology based on the radiolabelling of apoB-100 of native LDL (nLDL) and oxLDL, respectively, with the positron emitter fluorine-18 ((18)F) by conjugation with N-succinimidyl-4-[(18)F]fluorobenzoate ([(18)F]SFB). Radiolabelling of both nLDL and oxLDL using [(18)F]SFB causes neither additional oxidative structural modifications of LDL lipids and proteins nor alteration of their biological activity and functionality, respectively, in vitro. The method was further evaluated with respect to the radiopharmacological properties of both [(18)F]fluorobenzoylated nLDL and oxLDL by biodistribution studies in male Wistar rats. The metabolic fate of [(18)F]fluorobenzoylated nLDL and oxLDL in rats in vivo was further delineated by dynamic positron emission tomography (PET) using a dedicated small animal tomograph (spatial resolution of 2 mm). From this study we conclude that the use of [(18)F]FB-labelled LDL particles is an attractive alternative to, e.g., LDL iodination methods, and is of value to characterize and to discriminate the kinetics and the metabolic fate of nLDL and oxLDL in small animals in vivo.

Animals↗
PubMed2005

Principles of quantitative positron emission tomography.

The central distinguishing feature of positron emission tomography (PET) is its ability to investigate quantitatively regional cellular and molecular transport processes in vivo with good spatial resolution. This review wants to provide a concise overview of the established principles underlying quantitative data evaluations of the acquired PET images. Especially, the compartment modelling framework is discussed on which virtually all quantification methods utilized in PET are based. The aim of the review is twofold: first, to provide the reader with an idea of the theoretical framework and mathematical tools and second, to enable an intuitive grasp of the possibilities and limitations of a quantitative approach to PET data evaluation. This should facilitate an understanding of how PET measurements translate into quantities such as regional blood flow, volume of distribution, and metabolic rates of specific substrates.

Animals↗
PubMed2003

Positron emission tomography with 11C-acetate and 18F-FDG in prostate cancer patients.

Visualisation of primary prostate cancer, its relapse and its metastases is a clinically relevant problem despite the availability of state-of-the-art methods such as CT, MRI, transrectal ultrasound and fluorine-18 fluorodeoxyglucose positron emission tomography ((18)F-FDG PET). The aim of this study was to evaluate the efficacy of carbon-11 acetate and (18)F-FDG PET in the detection of prostate cancer and its metastases. Twenty-five patients were investigated during the follow-up of primary prostate cancer, suspected relapse or metastatic disease using (11)C-acetate PET; 15 of these patients were additionally investigated using (18)F-FDG PET. Fourteen patients were receiving anti-androgen treatment at the time of the investigation. Lesions were detected in 20/24 (83%) patients using (11)C-acetate PET and in 10/15 (75%) patients using (18)F-FDG PET. Based on the results of both PET scans, one patient was diagnosed with recurrent lung cancer. Median (18)F-FDG uptake exceeded that of (11)C-acetate in distant metastases (SUV =3.2 vs 2.3). However, in local recurrence and in regional lymph node metastases, (11)C-acetate uptake (median SUVs =2.9 and 3.8, respectively) was higher than that of (18)F-FDG (median SUVs =1.0 and 1.1, respectively). A positive correlation was observed between serum PSA level and both (11)C-acetate uptake and (18)F-FDG uptake. (11)C-acetate seems more useful than (18)F-FDG in the detection of local recurrences and regional lymph node metastases. (18)F-FDG, however, appears to be more accurate in visualising distant metastases. There may be a role for combined (11)C-acetate/(18)F-FDG PET in the follow-up of patients with prostate cancer and persisting or increasing PSA.

Acetates↗
PubMed2003

Intraindividual comparison of [11C]acetate and [11C]choline PET for detection of metastases of prostate cancer.

UNLABELLED: In a pilot trial we investigated whether significant differences in prostate cancer (PCA) imaging would be observed using [(11)C]acetate and [(11)C]choline positron emission tomography (PET). METHODS: Twelve patients were studied with both radiotracers. Whole body PET without attenuation correction was performed after injection of 0.95 +/- 0.15 GBq [(11)C]acetate and 0.84 +/- 0.13 GBq [(11)C]choline, respectively, from 5 to 60 min p. i. Focally increased uptake in bone, below the urinary bladder or in a lymph node region was considered as tumour. Primary tumour, lymph node involvement, bone metastases, local recurrence; and no evidence of disease were known in 2, 4, 2, 2; and 2 patients, respectively. RESULTS: [(11)C]Acetate uptake was highest in spleen and pancreas while [(11)C]choline uptake was predominant in liver and kidney parenchyma. However, interindividual variation was high. The potential of both radiotracers to detect known bone lesions, lymph node metastases, and imaging of the primary tumour was identical. However, both failed to detect a small local recurrence in two patients as well as to demonstrate lymph node involvement in one patient, which was confirmed by surgery. CONCLUSIONS: In this preliminary study, uptake of both radiotracers in prostate cancer or its metastases was nearly identical and none of them should be favoured. At present, both radiotracers influence patient management by detection of local recurrence, lymph node, or bone metastases of PCA.

Acetates↗
PubMed2001

Validation of myocardial blood flow estimation with nitrogen-13 ammonia PET by the argon inert gas technique in humans.

We simultaneously determined global myocardial blood flow (MBF) by the argon inert gas technique and by nitrogen-13 ammonia positron emission tomography (PET) to validate PET-derived MBF values in humans. A total of 19 patients were investigated at rest (n = 19) and during adenosine-induced hyperaemia (n = 16). Regional coronary artery stenoses were ruled out by angiography. The argon inert gas method uses the difference of arterial and coronary sinus argon concentrations during inhalation of a mixture of 75% argon and 25% oxygen to estimate global MBF. It can be considered as valid as the microspheres technique, which, however, cannot be applied in humans. Dynamic PET was performed after injection of 0.8 +/- 0.2 GBq 13N-ammonia and MBF was calculated applying a two-tissue compartment model. MBF values derived from the argon method at rest and during the hyperaemic state were 1.03 +/- 0.24 ml min-1 g-1 and 2.64 +/- 1.02 ml min-1 g-1, respectively. MBF values derived from ammonia PET at rest and during hyperaemia were 0.95 +/- 0.23 ml min-1 g-1 and 2.44 +/- 0.81 ml min-1 g-1, respectively. The correlation between the two methods was close (y = 0.92x + 0.14, r = 0.96; P < 0.0001). No indication was found for limited extraction of ammonia in the myocardium. The high concordance of global MBF values derived with argon and ammonia indicates that the implicit correction of spillover and recovery effects, incorporated in the model by including an effective blood volume parameter, works correctly quantitatively. Our data provide the previously missing human validation of MBF measurements from 13N-ammonia PET.

Adenosine↗
PubMed2001

Assessment of the incorporation of revascularized fibula grafts used for mandibular reconstruction with F-18-PET.

AIM: Determination of the range of regional blood flow and fluoride influx during normal incorporation of revascularized fibula grafts used for mandibular reconstruction. Evaluation, if healing complications are preceded by typical deviations of these parameters from the normal range. Assessment of the potential influence of using "scaled population-derived" instead of "individually measured" input functions in quantitative analysis. METHODS: Dynamic F-18-PET images and arterialized venous blood samples were obtained in 11 patients early and late after surgery. Based on kinetic modeling regional blood flow (K1) and fluoride influx (Kmlf) were determined. RESULTS: In uncomplicated cases, early postoperative graft K1--but not Kmlf--exceeded that of vertebrae as reference region. Kmlf values obtained in graft necrosis (n = 2) were below the ranges of values observed in uncomplicated healing (0.0113-0.0745 ml/min/ml) as well as that of the reference region (0.0154-0.0748). Kmlf values in mobile non-union were in the lower range--and those in rigid non-union in the upper range of values obtained in stable union (0.0211-0.0694). If scaled population-derived instead of measured input functions were used for quantification, mean deviations of 23 +/- 17% in K1 and 12 +/- 16% in Kmlf were observed. CONCLUSIONS: Normal healing of predominantly cortical bone transplants is characterized by relatively low osteoblastic activity together with increased perfusion. It may be anticipated that transplant necrosis can be identified by showing markedly reduced F- influx. In case that measured input functions are not available, quantification with scaled population-derived input functions is appropriate if expected differences in quantitative parameters exceed 70%.

Adult↗
PubMed2001

[1-(11)C]Acetate as a quantitative perfusion tracer in myocardial PET.

UNLABELLED: Our objective was to investigate the properties of [1-(11)C]acetate as a quantitative perfusion tracer for myocardial PET studies. METHODS: We determined the flow dependence of the effective acetate extraction by a comparison with [(13)N]ammonia in 24 patients at rest (n = 8) and under pharmacologic vasodilation (n = 16). Furthermore, we compared the statistical quality of the perfusion values derived with both tracers. Quantification was based on an irreversible 2-compartment model for [(13)N]ammonia and a reversible 1-compartment model for [1-(11)C]acetate. Area-conserving polar maps were used to determine the correlation between the unidirectional uptake parameters of both tracers on a pixel-by-pixel basis for the whole left ventricular myocardium. RESULTS: A fit of a generalized Renkin-Crone formula to the data yielded the unidirectional acetate extraction fraction E(f) = 1 - 0.64e(-1.20/f). An extraction correction based on this formula led to good quantitative agreement of perfusion values derived with [(13)N]ammonia and [1-(11)C]acetate over the whole observed flow range (average difference of flow values, 3%; correlation coefficient, 0.96). This agreement proved the applicability of acetate as a quantitative perfusion tracer even under stress conditions. An analysis of the statistical properties of the parameter estimates showed, moreover, that statistical errors were reduced by a factor of nearly 2 in comparison with ammonia. CONCLUSION: [1-(11)C]acetate allows accurate quantification of myocardial perfusion with PET at rest as well as under stress conditions. The use of acetate leads to distinctly improved statistical accuracy for the perfusion estimates in comparison with ammonia. This accuracy facilitates the generation of reliable parametric polar maps, which are especially useful for clinical application of myocardial perfusion quantification.

Acetic Acid↗
PubMed2000

Myocardial viability assessed by positron emission tomography in infants and children after the arterial switch operation and suspected infarction.

OBJECTIVES: The aim of the study was to assess regional glucose metabolism and contractile function by gated positron emission tomography using fluoro-18-deoxyglucose (FDG-PET) in pediatric patients after the arterial switch operation and suspected myocardial infarction. BACKGROUND: Morbidity and mortality after the arterial switch operation for transposition of the great arteries are often related to impaired coronary function. Justification of high-risk revascularization procedure in infancy requires thorough evaluation of myocardial viability. Although PET is state-of-the-art for evaluation of myocardial viability in adults there are no reports on its impact and feasibility in infants and children. METHODS: We applied electrocardiogram-triggered FDG-PET for assessment of metabolic and functional status of the myocardium in seven infants and seven children. Glucose metabolism, wall motion and wall thickening were evaluated visually and quantitatively on the basis of parametric 3-D images. Additionally, single-photon emission computed tomography perfusion scan was performed in six children. RESULTS: In two of seven infants, FDG-PET demonstrated viable myocardium in akinetic or hypokinetic regions corresponding to a coronary artery stenosis or occlusion. Therefore, indication for revascularization was derived from this finding. In six of the seven children, impaired glucose uptake reflecting myocardial scarring was present. Two patients had pathological findings on coronary angiography and signs of ischemia but were not suitable for revascularization. CONCLUSIONS: Myocardial viability and contractile function can be assessed simultaneously by gated FDG-PET even in infant hearts. This method contributes pertinent information to guide further therapy after the arterial switch operation and suspected myocardial infarction.

Adolescent↗
PubMed1999

Positron emission tomography and cholangiocarcinoma in primary sclerosing cholangitis.

We present the case of a 44-year-old male patient with a history of primary sclerosing cholangitis who developed a cholangiocarcinoma with pulmonary metastasis. The cholangiocarcinoma was identified in the PET scan by its enhanced 18F-FDG-uptake. Prospective studies should be performed to demonstrate whether PET will be suited to detect small and early cholangiocarcinomas, particular in young patients, who could be treated immediately and curatively by liver transplantation.

Adult↗
PubMed1997

Assessment of myocardial viability by use of 11C-acetate and positron emission tomography. Threshold criteria of reversible dysfunction.

BACKGROUND: Dual positron emission tomography (PET) imaging with a perfusion tracer and 18F-fluorodeoxyglucose (FDG) can detect myocardial viability. This approach may be replaced by a single 11C-acetate study, which enables quantification of both regional blood flow and oxidative metabolism. The significance of acetate-derived indexes for myocardial viability is examined. METHODS AND RESULTS: Thirty postinfarct patients with akinetic ventricular segments, a mean ejection fraction of 42 +/- 11%, and high-grade coronary obstructions were studied with serial 11C-acetate PET scanning before and 7 +/- 5 months after coronary revascularization. Acetate PET was tested against FDG and serial assessments of segmental wall motion. Sixty of 155 severely dysfunctional LV segments improved postoperatively, and regional blood flow increased. Flow estimates after revascularization suggested little fibrosis in reversible segments. At baseline, blood flows differed between normal myocardium, reversible dysfunction, and irreversible dysfunction (1.04 +/- 0.27, 0.73 +/- 0.18, and 0.43 +/- 0.18 mL.min-1.g-1, respectively; P < .001). Oxidative metabolic rates were reduced only in irreversibly injured LV segments. Multivariate analysis identified the acetate perfusion index as the only independent predictor of postoperative recovery. Its predictive accuracy was similar to that of FDG imaging but superior to indexes of flow-metabolic mismatch or oxidative metabolism. CONCLUSIONS: After myocardial infarction, quantitative indexes of perfusion and oxidative metabolism from acetate PET indicate a critical threshold beyond which tissue is irreversibly injured. Findings support the use of blood flow as a marker of myocardial viability in chronic postinfarct patients with modestly reduced ejection fractions.

Acetates↗
PubMed1997

Oxygen-15-water PET assessment of muscular blood flow in peripheral vascular disease.

UNLABELLED: To assess quantitatively regional nutritive muscular blood flow in patients with peripheral vascular disease (PVD), we evaluated the utility of PET with 15O-water. METHODS: Eight healthy volunteers and 16 patients with angiographically proven PVD were studied. Regional blood flow of the calf was measured with 15O-water PET during rest, after intra-arterial infusion of prostaglandin E1 and during ergometry. The studies were quantified using a one tissue compartment model. RESULTS: Normalized mean tracer uptake from 15-60 sec correlated closely (r = 0.98) with absolute blood flow. Scan times longer than 90 sec were required to determine blood flow reliably. The flow values were overestimated by 2% if arterial blood volume was neglected or if the input function delay was corrected globally for parametric imaging. Mean blood flow of calf muscles at rest did not differ significantly between patients (0.017 +/- 0.006 ml/min/ml) and control subjects (0.018 +/- 0.010 ml/min/ml). In PVD patients, blood flow increased by 100% after intra-arterial infusion of PGE1 in the respective leg. In the control subjects, average flow increased by a factor of six during exercise. The increase was more pronounced in the extensor muscles (0.182 +/- 0.031 ml/min/ml) than in flexor muscles (0.121 +/- 0.045 ml/min/ml). Due to the specific type of ergometry, superficial flexors exhibited higher flow values than the profound ones. CONCLUSION: PET with 15O-water enables reliable determination of regional nutritive skeletal muscle blood flow for research and clinical applications in patients with PVD.

Adult↗
PubMed1996

A kinetic model for cardiac PET with [1-carbon-11]-acetate.

UNLABELLED: Carbon-11-labeled acetate is a unique tracer for noninvasive assessment of myocardial oxidative metabolism with PET. Because adequate kinetic models have been missing, data evaluation in the past was performed mostly with phenomenological approaches such as mono- or biexponential fitting which cannot account for the influence of finite input duration and blood volume encountered in noninvasive PET investigations. METHODS: To investigate to what extent the current data evaluation schemes are justified, we developed a comprehensive model of [1-11C]-acetate kinetics in the myocardium which incorporates five tissue compartments: free acetate, activated acetate, CO2 precursors, amino acids and CO2. We derived the analytical solution of the model equations which is used for simulations and data fitting. RESULTS: The five-compartment model can reproduce in detail known experimental data. The resulting values of the eight model parameters compare favorably with existing biochemical facts. We have established the relation between parameters of the detailed model and one- and two-compartment models used for the evaluation of PET investigations. CONCLUSION: The kinetics of [1-11C]-acetate are adequately described by a five-compartment model. One- and two-compartment models are sufficient for simultaneous quantitative assessment of myocardial oxidative metabolism and perfusion with [1-11C]-acetate and PET.

Acetates↗
PubMed1996

A compartmental model for alveolar clearance of pertechnegas.

UNLABELLED: The washout of an inhaled water soluble radiotracer from the lungs is a measure of alveolar integrity. Data evaluation of 99mTc-DTPA studies were previously performed mainly with monoexponential fitting with or without background subtraction. The introduction of 99mTc-pertechnegas for the assessment of alveolar permeability necessitates the investigation of adequate data evaluation schemes for this radiotracer. METHODS: We developed a three-compartmental model to describe 99mTc-pertechnegas kinetics after inhalation. Monoexponential fitting of the first 5 min was investigated as simplification for clinical use. Different background corrections based on blood samples or representative regions of interest were compared. RESULTS: Correction of intra- and extravascular background by subtraction of calibrated curves, which are derived from blood or background areas, resulted in monoexponential washout curves. Clearance rates based on the three-compartmental model were nearly the same as those derived from a monoexponential fit after blood-activity subtraction (r = 0.96). A monoexponential analysis of the first 5 min without any background correction correlates well with the first component of the biexponential analysis (r = 0.97). CONCLUSION: A dynamic study of more than 45 min allows quantitative determination of the transfer rate of 99mTc-pertechnegas from the alveoli into the blood using compartmental analysis. A simplified monoexponential analysis of the first 5 min allows assessment of lung clearance without any background correction.

Administration, Inhalation↗
PubMed1995

Evaluation of the incorporation of bone grafts used in maxillofacial surgery with [18F]fluoride ion and dynamic positron emission tomography.

This study investigates the incorporation of bone grafts used in maxillofacial surgery by means of [18F]fluoride ion and positron emission tomography (PET). It considers patients who received pedicle grafts for mandibular reconstruction or onlay grafts for alveolar ridge augmentation. Dynamic PET images and arterialized venous blood samples were obtained within a 1-h period after i.v. injection of [18F]fluoride. Assuming a three-compartment model and applying multilinear least squares fitting, bone blood flow (K1) and fluoride influx (Kmlf) were determined. Additionally Patlak plot analysis was used to calculate fluoride influx (Kpat). In cervical vertebral bodies as the reference region, mean values for flow of K1 = 0.1162 +/- 0.0396 ml/min/ml and influx of Kmlf = 0.0508 +/- 0.0193 and Kpat = 0.0385 +/- 0.0102 ml/min/ml were found. Essentially these figures are comparable with physiological values in animal and man reported in the literature. Early after surgery a significant increase in flow and influx compared to vertebral bodies was observed in the regions of osteosyntheses between grafts used for reconstruction and recipient bone (K1 = 0.2181, Kmlf = 0.1000 and Kpat = 0.0666 ml/min/ml) and in onlay grafts (K1 = 0.2842, Kmlf = 0.1637 and Kpat = 0.0827 ml/min/ml). At the same time pedicle grafts showed a significant increase in flow but not in influx (K1 = 0.2042, Kmlf = 0.0774 and Kpat = 0.0529 ml/min/ml). Furthermore Kpat was significantly lower in pedicle grafts than in onlay grafts. In follow-up studies a significant decrease in flow occurred in pedicle grafts and the regions of osteosyntheses. Moreover the latter showed a significant decrease in Kmlf as well. It is concluded that [18F(-)] PET depicted increased blood flow and osteoblastic activity in onlay grafts and regions of osteosyntheses, indicating bone repair in the graft and adjacent host bone early after surgery. For the regions of osteosyntheses the decrease in both parameters corresponded to uncomplicated healing. The lack of increased influx, although flow was increased in pedicle grafts, most likely indicates that some necrosis occurred in these grafts despite patency of anastomoses. It may be concluded that [18F(-)] PET provides further insight into the biology of graft incorporation.

Adult↗
PubMed1995

[Coronary reserve after orthotopic heart transplantation: quantification with N-13 ammonia and positron emission tomography].

Coronary transplant vasculopathy is known to be associated with an early impairment of endothelium-dependent vasodilatation. In this study the largely endothelium-independent dilator response to dipyridamole was evaluated in 22 patients 36 +/- 17 months after transplantation in relation to their angiographic findings. The dipyridamole coronary reserve was measured by N-13 ammonia and positron emission tomography (PET). Transplant vasculopathy was suspected or evident in 13 of 22 patients by coronary angiography. Coronary reserve was lower in transplant recipients than in normal controls (2.3 +/- 0.9 vs. 4.7 +/- 1.4). Those with a normal angiogram had a near normal minimal coronary resistance (0.3 +/- 0.04 mmHg.min.100 g/ml) and a normalized coronary reserve after correction for the increased resting blood flow (4.8 +/- 0.7). However, in patients with angiographic vasculopathy, coronary reserve was markedly reduced (1.8 +/- 0.7, corrected 2.7 +/- 1.0) and minimal coronary resistance was elevated (0.6 +/- 0.3, p < 0.001). Moreover, regional coronary reserve was homogeneously reduced throughout the myocardium without a clear segmental relationship to angiographic stenoses. After testing of other factors known to influence coronary resistance, our data are compatible with diffuse obstructions of the microvascular bed that are associated with an angiographically visible vasculopathy. The evaluation of coronary reserve by dipyridamole and PET provides a useful extension of angiography in these patients.

Adult↗