R. A. Dierckx

Fluorine-18 fluorodeoxyglucose-positron 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.

Is there a role for agonist gastrin-releasing peptide receptor radioligands in tumour imaging?

Gastrin-releasing peptide (GRP) has been shown to be a tumour growth stimulating agent for a number of normal and human cancer cell lines. The tumour growth effect is a direct result of GRP binding to membrane G-protein coupled GRP receptors (GRP-R) on the cell surface. Available data on the role of GRP and GRP-R in human lung, prostate, breast, colorectal and gastric carcinoma are reviewed and it is suggested that radiolabelled agonists are preferable to antagonists for imaging and therapy as they appear to be internalised, yielding a higher target/background ratio. The use of rhenium or indium radiolabels for therapy may provide a new approach to GRP/bombesin expressing tumours.

55Co-EDTA for renal imaging using positron emission tomography (PET): a feasibility study

The feasibility of imaging renal function with 55Co-ethylene diamine tetraacetic acid (EDTA) and dynamic positron emission tomography was investigated. A group of normal Wistar rats was injected intravenously with 55Co-EDTA and underwent dynamic positron emission tomography (PET) imaging in order to study the biodistribution. The time-activity curves of the heart (blood pool), both kidneys, liver, and bladder were observed. In two animals, blood and urinary clearances of 55Co-EDTA were compared with those for 51Cr-EDTA. In one animal, unilateral reduction in kidney function was induced and the right/left ratio for the kidneys was determined. The time-activity curves showed that 55Co-EDTA cleared rapidly from the blood pool (heart), whereas prompt and high target-to-background ratios for both kidneys were obtained. The entire tracer was cleared from the renal parenchyma by urinary excretion and collection of the activity in the bladder. No specific activity uptake was noticed in any other organ or tissue. The clearances of 55Co-EDTA and 51Cr-EDTA in blood were not significantly different, showing that the nature of the M++ has no influence on the in vivo behavior of EDTA. 55Co can be produced easily by cyclotron irradiation and 55Co-EDTA is a promising physiological tracer for nephrological research using PET.

The classical stroop interference task as a prefrontal activation probe: a validation study using 99Tcm-ECD brain SPECT

This study investigated the feasibility of brain single photon emission computed tomography (SPECT) functional imaging in a neuropsychological test setting, following a single-day protocol with a split-dose paradigm. The Stroop Color Word Test (SCWT) is an example of a well-documented prefrontal activation task. In a split-dose protocol, ten right-handed healthy volunteers were injected twice with 370 MBq 99Tcm-ethyl cysteinate dimer while performing consecutively both series of card-reading of the SCWT. Images were reconstructed using filtered back-projection and normalized to a standard template in Talairach coordinates. Statistical Parametric Mapping (SPM96) was used to determine voxelwise significant changes. A first activation cluster was found in the left medial prefrontal cortex, consisting of the gyrus cinguli anterior and the gyrus frontalis medius and superior. A second activation cluster included the right gyrus frontalis dorsalis and medius. These findings confirm to a large extent the results of previous functional magnetic resonance imaging, positron emission tomography studies of Stroop-like tasks. The choice and validity of various methodological characteristics of the experimental design leading to these results is critically discussed. It is concluded that brain SPECT activation with the Stroop Color Word Test under standard neuropsychological conditions in healthy volunteers, is both technically and practically feasible.

Biodistribution and dosimetry study of 123I-rh-annexin V in mice and humans.

Summary This study reports on the optimization of the labelling procedure of clinical grade 123I‐rh‐annexin V and on the investigation of the biodistribution and dosimetry of 123I‐rh‐annexin V, a tracer proposed for the study of apoptosis in mice and humans. Research grade 123I‐rh‐annexin V was prepared as described previously, whereas clinical grade 123I‐rh‐annexin V was prepared according to a modified IodoGen method. NMRI mice, 3–4 weeks of age, received research grade 123I‐rh‐annexin V (74.0 + 3.7 kBq/mouse) by intravenous (i.v.) injection and killed at preset time points. Afterwards, the collected organs, blood, urine and faeces were counted for radioactivity and determined as %ID/g tissue or %ID over time. Secondly, six volunteers with normal liver and kidney function underwent whole‐body scans up to 21 h after i.v. injection of clinical grade 123I‐rh‐annexin V (345 ±38 MBq). Time‐activity curves were generated for the organs of interest, e.g., thyroid, heart, liver, kidneys and whole body, by fitting the organ specific geometric mean counts, obtained from region of interest analysis of acquired images in humans. The MIRD formulation was applied to calculate the absorbed radiation doses for various organs. Clinical grade 123I‐rh‐annexin V was obtained in radiochemical yields of 87.0 + 6.5% and radiochemical purities >98%. In mice, research grade 123I‐rh‐annexin V accumulated primarily in liver, kidney, stomach and lung tissue, limiting its usefulness for imaging of ongoing apoptosis in the abdominal and thoracic region. Clearance was predominantly urinary. In humans, acquired images with the clinical grade radioligand showed low lung uptake, resulting in good imaging conditions for the thoracic region. On the other hand, delayed imaging of the abdominal region was impeded due to extensive bowel activity. The highest absorbed doses were received by the thyroid, the kidneys, the heart wall, the liver and bone surfaces. The average effective dose of 123I‐rh‐annexin V was estimated to be 0.02 mSv·MBq‐1. The amount of 123I‐rh‐annexin V required for in vivo imaging, results in an acceptable effective dose to the patient.

Estimation of risk based on biological dosimetry for patients treated with radioiodine.

A multicentre study was undertaken to assess the cytogenetic damage to peripheral blood lymphocytes in 31 patients treated with 131I for thyrotoxicosis using the cytokinesis-blocked micronucleus assay. The results were compared to those for eight thyroid carcinoma patients using the same method. For each patient, blood samples were taken immediately before and 1 week after iodine administration. The first blood sample was divided into three fractions and each fraction was subsequently irradiated in vitro with 0, 0.5 and 1 Gy 60Co gamma rays, respectively. After blood culture for 70 h, cells were harvested, stained with Romanowsky-Giemsa and the micronuclei scored in 1000 binucleated cells. For both patient groups, a linear-quadratic dose-response curve was fitted through the data set of the first blood sample by a least squares analysis. The mean increase in micronuclei after 131I therapy (second blood sample) was fitted to this curve and the mean equivalent total body dose (ETBD) calculated. Surprisingly, in view of the large difference in administered activity between thyroid carcinoma patients and thyrotoxicosis patients, the increase in micronuclei after therapy (mean +/- S.D.: 32 +/- 30 and 32 +/- 23, respectively) and the equivalent total body dose (0.34 and 0.32 Gy, respectively) were not significantly different (P > 0.1). The small number of micronuclei induced by 131I therapy (32 +/- 29), compared with external beam radiotherapy for Hodgkins disease (640 +/- 381) or cervix carcinoma (298 +/- 76) [1], gave a cancer mortality estimate of less than 1%. This also explains why late detrimental effects in patients after 131I treatment have not been reported in the literature.

Urinary α1-microglobulin detects uropathy. A prospective study in 483 urological patients

Abstract Purpose: The aim of the study was to evaluate prospectively urinary α1-microglobulin as a marker of proximal tubular damage following acute pyelonephritis and outflow disease of the upper urinary tract in a urological population with minimal exclusion criteria. We also measured the urinary γ-glutamyltransferase activity, urinary albumin, urinary and serum creatinine, serum IgA and serum α1-microglobulin. Patients and methods: We studied 483 urological patients (age: 1 to 92 years, 297 men, 186 women) excluding patients receiving nephrotoxic drugs, or suffering from type 1 diabetes or renal diseases. There were 141 patients with urinary tract infection but no fever, 36 patients with high fever of non-renal origin, 51 patients with acute pyelonephritis and 156 patients with outflow disease of the upper tract, and 99 patients were incluced in the reference population. Results: For acute pyelonephritis, vesico-ureteral reflux, and ureteral obstruction, urinary α1-microglobulin had a sensitivity of 94%, 90% and 63% respectively and a specificity of 67%, 77% and 76%. The area under the curve of the receiver operator characteristic curve was significantly (p < 0.001) higher for urinary α1-microglobulin than for albumin or γ-glutamyltransferase activity. Unexpected positive results were found in acute prostatitis. The urinary α1-microglobulin was the only parameter which differentiated between acute prostatitis and pyelonephritis (p < 0.001). Creatinine clearance or age had little and gender had no influence on the urinary excretion of α1-microglobulin. Urine production rate significantly increases the urinary α1-microglobulin/creatinine ratio. Conclusion: Our results suggest that the urinary α1-microglobulin/creatinine ratio is a diagnostically useful marker of tubular damage in acute pyelonephritis and vesico-ureteral reflux in the urological population. Following renal colic and chronic ureteral obstruction, a significant increase in urinary α1-microglobulin excretion was observed.

QT dispersion is not related to infarct size or inducibility in patients with coronary artery disease and life threatening ventricular arrhythmias

OBJECTIVE To relate QT parameters to infarct size and inducibility during electrophysiological studies. DESIGN Analysis of a prospective register. SETTING University hospital. PATIENTS 64 patients with coronary artery disease and documented life threatening ventricular arrhythmias. INTERVENTIONS Measurements of QT-max, QTc-max, and QT dispersion (QT-d) on a simultaneous 12 lead ECG (50 mm/s). Estimation of myocardial infarct size with radionuclide left ventricular ejection fraction (LVEF), echocardiography (left ventricular end diastolic diameter, LVEDD), and a defect score based on a quantitative stress redistribution 201-thallium perfusion study. Electrophysiological study to assess inducibility. RESULTS Mean (SD) QT parameters were: QT-max 440 (50) ms, QTc-max 475 (46) ms, and QT-d 47 (20) ms. Mean (SD) estimates of infarct size were: LVEF 34 (13)%, LVEDD 61 (9) mm, and defect score 18 (11). There was no significant correlation between any index of infarct size and QT parameters. QT parameters were not significantly different between patients with inducible (n = 57) and non-inducible arrhythmias (n = 7) (QT-max: 416 (30) v 443 (51) ms, p = 0.18; QTc-max 485 (34) v 473 (47) ms, p = 0.34; QT-d 47 (12) v 47 (21) ms, p = 0.73). Non-inducible patients had a significant lower defect score: 8 (9)v 19 (11), p = 0.02, but comparable LVEF: 38 (12)% v 34 (12)%, p = 0.58, and LVEDD: 54 (10) v 61 (8) mm, p = 0.13. CONCLUSIONS QT parameters are not influenced by infarct size and do not predict inducibility during electrophysiological study in patients with coronary artery disease and malignant ventricular arrhythmias. In contrast, the amount of scar tissue determined by perfusion imaging is strongly correlated with inducibility.

The anti-tumoral activity of neoadjuvant intra-arterial 131I-lipiodol treatment for hepatocellular carcinoma: a pilot study.

BACKGROUND The high recurrence rate after curative resection has stimulated the development of adjuvant treatment modalities, such as local embolization. This study was set up to investigate the anti-tumoral potential of neo-adjuvant 131I-lipiodol administration before liver transplantation. METHODS In this preliminary, prospective study we treated 10 consecutive HCC patients by intra-arterial injection of 131I-lipiodol into the hepatic artery followed by liver transplantation within 1-9 months (mean 3.4). After hepatic catheterization, 1332-2146 MBq (mean 1887 MBq) or 36-58 mCi (mean 51 mCi) was instilled as selective as possible, depending on the distribution of the tumors: non-selectively in the hepatic artery propria (n = 4), selectively in the right and/or left hepatic artery (n = 3) or super-selectively in segmental arteries (n = 3). RESULTS Anti-tumoral activity was regarded as obvious with 1) a strong decrease of alfa-fetoprotein (AFP), comparing the highest recorded value before and after 131I-lipiodol and/or 2) a downstaging in TNM classification on the posttherapy MRI as compared to the pre-therapy MRI and/or 3) tumors with > 50% necrosis on histo-pathology of the explanted liver, without previous chemoembolization. Either of these criteria were met by 5/10 (50%) of patients. A 4) downstaging in pTNM classification on histopathology compared to the TNM classification of the MRI and/or a 5) tumor necrosis of only 10-50% were regarded as possibly tumor-related but were not accepted as a single criteria of anti-tumoral activity. This was seen in 3/10 (30%) of patients. Clinical side-effects of the 131I-lipiodol therapy were generally mild with a temperature rise in two cases, nausea without vomiting in another two and upper back pain in one patient. In one patient progressive liver failure developed one week after 131I-lipiodol therapy necessitating premature liver transplantation after 4 weeks. CONCLUSION With the use of stringent anti-tumoral criteria, this study shows evidence of an anti-tumoral effect in 50% of patients. Our data support the evaluation on larger patient numbers to confirm the promising anti-tumoral activity of 131I-lipiodol in HCC patients candidated for liver transplantation.

Biodistribution and displacement studies of the selective 5-HT2Areceptor antagonist 123I-5-I-R91150 in the normal dog

There is increasing interest in mapping receptors in vivo by using functional imaging modalities such as single photon emission tomography (SPET) and positron emission tomography (PET). Since SPET is a more accessible functional imaging modality than PET and, overall, it is more economical, radioligands suitable for this technique are in greater demand. Recently, 123I-5-I-R91150, a radioligand with high selectivity and affinity for 5-HT2A receptors in the brain, was introduced for SPET. This study reports on the whole-body distribution and brain uptake of the selective 123I-5-I-R91150 ligand in four normal dogs. The frontal to cerebellar ratio of uptake in time was determined in three dogs. Time-activity curve of venous blood was determined in one dog. Maximal global brain uptake was found at 10-60 min post-injection. Higher brain uptake was noted in the frontal cortical areas compared to the cerebellum. The frontal-cerebellar ratio reached the highest values at 90-180 min. Reversibility and pharmacological selectivity of ligand binding was demonstrated through displacement and blocking studies with the 5-HT2A receptor antagonist ketanserin. This study demonstrates that the specific 5-HT2A iodinated ligand can be used for imaging and semi-quantification of the 5-HT2A receptors in the canine brain in vivo by using SPET.