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The [13C]acetate breath test accurately reflects gastric emptying of liquids in both liquid and semisolid test meals

BACKGROUND/AIMS The current standard for gastric emptying studies are radioactive isotope methods. [13C]breath tests have been developed as a nonradioactive alternative. The aim of this study was to validate a [13C]acetate breath test as a measure of gastric emptying of the liquid phase both in liquid and semisolid test meals by simultaneous radioscintigraphy. METHODS Thirty-five patients with dyspeptic symptoms and 20 healthy volunteers were tested using a semisolid oatmeal or a liquid test meal. Both test meals were labeled by 150 mg sodium [13C]acetate and (in patients) by 45 MBq 99mTc-albumin colloid. Half-time of gastric emptying was calculated after curve fitting of the 13C exhalation to a modified power exponential function. 99mTc-albumin emptying was measured by conventional radioscintigraphy. RESULTS The half-emptying times for the [13C]acetate breath test closely correlated to those measured by radioscintigraphy both for semisolids (r = 0.87) and liquids (r = 0.95). The time of maximum 13CO2 exhalation was itself a reliable parameter compared with the half-emptying times obtained by scintigraphy (r = 0.85 for semisolids; r = 0.94 for liquids). CONCLUSIONS The [13C]acetate breath test is a reliable and noninvasive tool for the analysis of gastric emptying rates of liquid phases without radiation exposure.

99Tcm-labelled anti-CEA monoclonal antibody for tumour immunoscintigraphy: first clinical results

Twenty patients with malignant carcinoembryonic antigen (CEA)-producing tumour recurrences (colorectal n = 14; breast, lung, medullary thyroid carcinoma n = 2, each) were studied by immunoscintigraphy using an intact monoclonal anti-CEA antibody (BW 431/26) labelled with 99Tcm by a new labelling technique (Schwarz Method). This novel approach allows an almost quantitative labelling of the antibody, which is first reduced using a thiol, lyophilized in purified form, and then reacted with a stannous salt component before 99Tcm-pertechnetate binding. The labelling efficiency (as controlled by TLC) was > 95%, the in vitro stability at least 6 h. The imaging results (planar and SPECT) yielded a sensitivity of 91%, a specificity of 87% and a diagnostic accuracy of 90%.These first promising clinical results trigger the hope that the successful labelling of monoclonal antibodies with 99Tcm is a decisive step towards the more practically orientated use of tumour immunoscintigraphy.

Positron Emission Tomography (PET) for Staging and Evaluation of Response to Treatment in Patients with Hodgkin's Disease

Forty two examinations utilizing F-18 FDG-PET were performed in 23 patients with Hodgkins disease to study for involved lymphoma regions and compared to conventional staging procedures. Twenty stagings were performed at diagnosis of untreated Hodgkins disease or at first relapse, and 22 restagings during and after chemoradiotherapy. At diagnosis in 5 of 20 patients PET and other procedures revealed different extranodal manifestations and in 3 patients established different clinical staging. PET seemed to be accurate in the assessment of lymphoma involvement in nodal sites. During follow up, in 10 out of 22 investigations different results and discrepancy were recorded, mostly due to the different extent of F-18-FDG metabolism in residual masses in lymphatic tissues compared to CT, X-ray or ultrasonography. The results indicate that PET may have advantages in the assessment of remissions in nodal sites. Less conclusive results were observed with regard to extranodal involvement or inflammatory disease. In conclusion PET may be sufficient for the staging of the majority of patients with Hodgkins disease and particularly for assessing remission status in nodal sites, but PET may have disadvantages in the evaluation of extranodal lymphoma and inflammatory disease.

Metabolic (PET) and receptor (SPET) imaging of well- and less well-differentiated tumours: Comparison with the expression of the Ki-67 antigen

[111In-DTPA-D-Phe1]-pentetreotide has been shown to localize well-differentiated and slowly growing neuroendocrine tumours, whereas increased FDG uptake is associated with malignancy. This prospective study explores the role of metabolic (PET) and receptor (SPET) imaging in well- and less well-differentiated tumours--gastroenteropancreatic (GEP) tumours, medullary thyroid carcinomas (MTC) and thymic carcinomas--in comparison with the expression of the Ki-67 antigen. Ten patients with GEP tumours, five with MTC and five with thymic carcinomas were studied. Prior to PET, somatostatin receptor scintigraphy (SRS) was performed in all patients. Sixty minutes after the intravenous administration of 18F-FDG (370 MBq), whole-body PET was performed. In addition, the resected tissues were prepared for immunocytochemistry examination (cell cycle-associated Ki-67 antigen). Preoperative SRS detected multiple primary tumours and metastatic lesions in four patients with well-differentiated carcinoids (low Ki-67 expression). Whole-body PET demonstrated normal distribution of FDG in all of these patients. In patients with recurrent MTC and rapidly increasing CEA levels, SRS showed no in vivo somatostatin receptor expression, whereas whole-body PET localized 24 locoregional lymph node metastases with increased FDG uptake. Immunocytochemistry of the resected lymph nodes demonstrated high Ki-67 expression associated with a high proliferative activity. Similar results in receptor scintigraphic and metabolic behaviour were obtained from patients with metastasizing thymic carcinomas (high Ki-67 expression). In conclusion, SRS has been shown to localize well-differentiated GEP tumours. In contrast, FDG PET is only valuable for predicting malignancy in less well-differentiated GEP tumours and malignant MTC associated with rapidly increasing CEA levels. Therefore, an additional 18F-FDG PET procedure should only be performed if SRS is negative. Furthermore, our preliminary results suggest that increased FDG metabolism reflects the invasiveness of thymic carcinomas.

PROGNOSTIC SIGNIFICANCE OF CORONARY FLOW RESERVE ON LEFT VENTRICULAR EJECTION FRACTION IN CARDIAC TRANSPLANT RECIPIENTS

BACKGROUND Cardiac allograft vasculopathy is a common phenomenon in epicardial and microvascular vessels. Intramyocardial vessel disease may lead to small, stellate infarcts. The present study tested the impact of microvascular vasomotor function on changes in left ventricular systolic function in the long-term follow-up after cardiac transplantation. METHODS Seventeen consecutive cardiac transplant patients, 40+/-21 months after cardiac transplantation, without angiographically visible cardiac allograft vasculopathy and without episodes of acute rejection were included in the study. Coronary microvascular reactivity was assessed by the endothelium-dependent stimulus acetylcholine (50 microg i.c.) and by the endothelium-independent stimulus dipyridamole (0.56 mg/kg i.v.) utilizing an Doppler catheter. Radionuclide ventriculography was performed at the time of coronary flow measurement and repeated 2 years later to correlate changes in left ventricular ejection fraction with the coronary flow reserve measurement 2 years previously. RESULTS There was a statistically significant correlation between endothelium- independent coronary flow reserve to dipyridamole and changes in ejection fraction at rest (r=0.59; P < 0.01) and during exercise (r=0.48; P < 0.05). Twenty-four months later, patients with a coronary flow reserve to dipyridamole < 2.5 showed a significant decline in ejection fraction during exercise (-7 +/- 5%) compared to patients with a coronary flow reserve > 2.5 (1.1+/-5%; P=0.003). Coronary flow reserve to acetylcholine was not correlated with a reduced ejection fraction during exercise. CONCLUSIONS Endothelium-independent microvascular dysfunction has prognostic importance for deterioration of left ventricular function in cardiac transplant recipients without angiographically visible coronary artery stenoses. These results reinforce the concept that microvascular and epicardial vessel disease after transplantation are two distinct entities with different functional consequences.

Can response to partial sleep deprivation in depressed patients be predicted by regional changes of cerebral blood flow

The possible predictive value of regional cerebral perfusion patterns with respect to the response to partial sleep deprivation (PSD) was evaluated in 15 major depressive patients (mean age = 54.9 years, mean Hamilton depression score = 21.6). Patients were studied with single photon emission computed tomography with technetium-99 m-D,L-hexamethyl-propylene amine oxime. Scans were performed on the morning before and after (at 08.00 h) PSD. Responders to PSD had significantly higher perfusion in the right orbitofrontal cortex than did non-responders before PSD. Multiple regression analysis indicated that right orbitofrontal/basal cingulate perfusion (r = -0.77, P < 0.001) before PSD, and left inferior temporal perfusion (r = 0.59, P = 0.01) after PSD, were fairly accurate predictors of change in Hamilton depression scores. Thus, it appears that the orbitofrontal cortex and the cingulate are involved in PSD and may serve as predictors of therapeutic response.

Stellenwert der18F-Fluordeoxyglucose-Positronen-emissionstomographie in der Radiotherapieplanung von Kopf-Hals-Tumoren

ZusammenfassungHintergrundEine exakte Ausbreitungsdiagnostik ist Voraussetzung für die individualisierte Bestrahlungsplanung bei Patienten mit Kopf-Hals-Tumoren. Trotz hoher Zuverlässigkeit der in der Routine eingesetzten Verfahren Computer-und Kernspintomographie ist die sichere Diagnostik eines lymphonodalen Tumorbefalls oft nicht möglich. Wir untersuchten im Rahmen einer Studie, ob die zusätzliche Durchführung einer18F-Fluordeoxyglucose-Positronenemissionstomographie (FDG-PET) hier einen für die Radiotherapieplanung relevanten Informationsgewinn erbringt.Patienten und MethodeUntersucht wurden Daten von 34 Patienten mit Plattenepitheltumoren der HNO-Region, bei denen im Rahmen des Staging vor Radiotherapieplanung zusätzlich zu Sonographie, MRT, CT und Panendoskopie eine FDG-PET durchgeführt wurde. Ausgewertet wurde, wie häufig und in welchem Ausmaß das Ergebnis der PET eine Änderung des geplanten Bestrahlungsfeldes bzw. des Behandlungskonzeptes erforderte.ErgebnisseBei 7/12 der Rezidive und 9/22 der Primärtumoren wurde durch die FDG-PET ein konventionell nicht festgestellter Tumorbefall diagnostiziert. In allen Fällen war eine Änderung des Therapiekonzeptes oder des Bestrahlungsvolumens erforderlich. Überdurchschnittlich häufig waren therapierelevante PET-Befunde bei Rezidivtumoren, großen Primärtumoren (T3 und T4) und bei Primärtumoren mit ausgedehntem Lymphknotenbefall (N2 und N3).SchlußfolgerungBesonders bei Rezidivtumoren und fortgeschrittenen Kopf-Hals-Tumoren erbringt die FDG-PET einen Gewinn an diagnostischer Information für die Radiotherapieplanung. Bei dieser Patientengruppe sowie bei unklarer Befundlage sollte die FDG-PET als zusätzliches diagnostisches Verfahren im prätherapeutischen Staging vor der Entscheidung über Therapiestrategie und Bestrahlungsplanung hinzugezogen werden.AbstractPurposeAn individualized radiation treatment planning in patients with head and neck tumors requires an exact definition of tumorspread. Despite of high reliability of methods like computed tomography, sonography or magnetic resonance imaging used in daily routine, the correct diagnosis of lymphonodal tumor infiltration is often not possible. In a prospective trial, we examined whether an additional FDG-PET gives a relevant gain of information for radiation treatment planning.Patients and MethodsWe studied data of 34 patients with histologically confirmed squamous cell carcinoma of the head and neck who received a FDG-PET prior to treatment planning additionally to conventional staging procedures. The extent of changes of treatment strategy or target volume due to additional FDG-PET finding were analyzed.ResultsIn 9/22 of patients with primary tumors and in 7/12 of patients with recurrent disease, FDG-PET detected additional tumor manifestations. In all cases, changes of treatment strategy or target volume were necessary. Regarding patients with primary tumors, the percentage of treatment modifications was highest in patients with large tumors (T3 and T4) and patients with advanced lymph node involvement (N2 and N3).ConclusionsEspecially in patients with recurrent disease and patients with advanced tumor stages, FDG-PET is able to give clinically relevant information compared to conventional staging procedures. Therefore, in these group of patients a FDG-PET study prior to radiotherapy planning should be considered.PURPOSE An individualized radiation treatment planning in patients with head and neck tumors requires an exact definition of tumorspread. Despite of high reliability of methods like computed tomography, sonography or magnetic resonance imaging used in daily routine, the correct diagnosis of lymphonodal tumor infiltration is often not possible. In a prospective trial, we examined whether an additional FDG-PET gives a relevant gain of information for radiation treatment planning. PATIENTS AND METHODS We studied data of 34 patients with histologically confirmed squamous cell carcinoma of the head and neck who received a FDG-PET prior to treatment planning additionally to conventional staging procedures. The extent of changes of treatment strategy or target volume due to additional FDG-PET findings were analyzed. RESULTS In 9/22 of patients with primary tumors and in 7/12 of patients with recurrent disease, FDG-PET detected additional tumor manifestations. In all cases, changes of treatment strategy or target volume were necessary. Regarding patients with primary tumors, the percentage of treatment modifications was highest in patients with large tumors (T3 and T4) and patients with advanced lymph node involvement (N2 and N3). CONCLUSIONS Especially in patients with recurrent disease and patients with advanced tumor stages, FDG-PET is able to give clinically relevant information compared to conventional staging procedures. Therefore, in these group of patients a FDG-PET study prior to radiotherapy planning should be considered.

Initial clinical results with technetium-99m-labeled ll2 monoclonal antibody fragment in the radioimmunodetection of b-cell lymphomas

Background. Various monoclonal antibodies (MoAb) labeled with Iodine‐131 or Indium‐111 (In‐111) have been investigated for radioimmunodetection of Hodgkins and non‐Hodgkins lymphomas. Successful radioimmuno‐therapy also has been reported. The purpose of this pilot study was to stage non‐Hodgkins B‐cell lymphomas (NHL) using whole body scintigraphy with technetium‐99m (Tc‐99m)‐labeled murine monoclonal antibody LL2 (EPB‐2) Fab′ (Immunomedics, Morris Plains, NJ). Others have shown this MoAb to have specific binding to B‐cell lymphomas by flow cytometry and immunofluorescence. Initial clinical studies by others have demonstrated targeting of NHL with the Tc‐99m‐labeled LL2‐Fab′.

Evaluation of the effects of total sleep deprivation on cerebral blood flow using single photon emission computerized tomography

HMPAO‐single photon emission computerized tomography (SPECT) is a useful technique in studying cerebral blood flow (CBF). This method is suitable to evaluate the differences of CBF with reference to total sleep deprivation (TSD) within 24 h because of the short half‐life of the radiopharmaceutical compound. In the present study, CBF before and after TSD was analysed in patients suffering from major depression. The morning before and after TSD, Tc‐HMPAO‐SPECT was performed in 20 patients. Hamilton Rating Scale for Depression scores and subjective ratings were obtained daily. Eleven patients responded to TSD; 9 were nonresponders. The main finding was a significant left temporal and mainly right parietal increase of CBF, which was observed in the responders only. CBF values and the severity of depression correlated inversely.

Multimodal imaging of residual function and compensatory resource allocation in cortical atrophy: a case study of parietal lobe function in a patient with Huntington's disease

In a case of Huntingtons disease (HD) with dementia and pronounced parieto-frontal atrophy, the functional state of the affected regions was investigated using functional magnetic resonance imaging (fMRI) and fluorodeoxyglucose-positron emission tomography (FDG-PET). It was observed that although parietal areas showed extensive atrophy and reduced resting glucose metabolism, the patient performed with similar accuracy but with longer response time in a visuospatial task compared with healthy control subjects. At the same time, the blood oxygen level-dependent (BOLD) fMRI signal in these areas, which are involved in visuospatial processing, showed a similar task-dependent modulation as in control subjects. The signal amplitude (signal percent change) of the task-dependent activation was even higher for the HD patient than in the control group. This residual functionality of parietal areas involved in visuospatial processing could account for the patients performance in the task concerned, which contrasted with his poor performance in other cognitive tasks. The increased percent-signal change suggests that a higher neuronal effort was necessary to reach a similar degree of accuracy as in control subjects, fitting well with the longer reaction time. We propose that fMRI should be considered as a tool for the assessment of functionality of morphologically abnormal cortex and for the investigation of compensatory resource allocation in neurodegenerative disorders.