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The current study aimed to determine the optimum diagnostic imaging technique out of magnetic resonance imaging (MRI), 18 F-fludeoxyglucose positron emission tomography/computed tomography ([ 18 F]FDG-PET/CT, otherwise known as PET/CT) and [ 18 F]FDG-PET/MRI (otherwise known as PET/MRI) for the pelvic lymph node staging (N-staging) of untreated cervical carcinoma (CC). A total of 27 patients were included in the present study. All patients had undergone pre-treatment with PET/CT and MRI ≤45 days prior to undergoing a lymphadenectomy. The results from PET (separated from PET/CT), MRI and the statistically combined results of (virtual) PET/MRI were compared to those from histological analyses (the gold standard). A per-patient-based analysis of the detection of pelvic lymph node metastases indicated that PET/MRI had a sensitivity of 64%. The specificity of PET/CT and MRI were 69 and 62%, respectively. The positive predictive value (PPV) was 69 and 64% for PET/CT and MRI, respectively. The negative predictive value (NPV) was 64 and 62% for PET/CT and MRI, respectively. The sensitivity of the PET-guided PET/MRI and the MRI-guided PET/MRI was 64% for both. The specificity of the PET-guided PET/MRI and the MRI-guided PET/MRI was 77 and 62%, respectively. The PPV was 75% for PET-guided PET/MRI and 64% for MRI-guided PET/MRI, and the NPV was 67 and 62%, respectively. PET/CT and the virtual PET/MRI exhibited the same low sensitivity (64%). PET/MRI exhibited slightly better results than PET/CT regarding specificity (77 vs. 69%, respectively), PPV (75 vs. 69%, respectively) and NPV (67 vs. 64%, respectively). The results of the present study suggested that PET/CT and MRI are not optimal diagnostic modalities, and that PET/MRI does not necessarily lead to better results than PET/CT, in the pelvic N-staging of CC.

Aim: To evaluate (18)F-fluorodihydroxyphenylalanine-positron emission tomography/ contrast-enhanced computed tomography ((18)F-DOPA PET/CT) for the detection of paragangliomas (PARA) without any patient selection, such as genetic predisposition for the development of these tumors, history of metastatic PARA or hormonal status., Patients and Methods: In this retrospective study, 28 consecutive patients (15 women, 13 men; mean age=46.4 years; age range=19-73 years), who were referred to our PET/CT center for the detection of clinically suspected PARA, were included. Final diagnosis was confirmed by histological reports of surgically proven lesions and/or clinical follow-up (including laboratory results and/or PET/CT follow-up)., Results: On a per-lesion basis (45 lesions) analysis, there was a sensitivity of 64.3% for CT, 73.8% for PET, 100% for PET/CT and a positive predictive value (PPV) of 93.1% for CT, 96.9% for PET and 100% for PET/CT. On a per-patient basis analysis, the sensitivity, specificity and accuracy for CT was 86.7%, 84.6% and 85.7%, respectively, and, for PET 80%, 100% and 89.3%, respectively, and, for PET/CT 100%., Conclusion: Based on our data, (18)F-DOPA PET/CT is a "one-stop diagnostic modality" for the assessment of patients with suspected PARA., (Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Aim: The American thyroid association (ATA) recommends that additional imaging procedures supplement cervical ultrasonography (US) in any patient with a basal calcitonin value above 150 pg/ml in the follow-up of medullary thyroid carcinoma (MTC). The aim of the present study was to reaffirm or challenge this cut-off for 18-Fluorine-Fluorodihydroxyphenylalanine positron emission tomography (18F-DOPA PET) and conventional imaging ultrasonography (US), computed tomography (CT), magnetic resonance imaging (MRI))., Materials and Methods: Thirty-nine patients (18 females, 21 males), mean age 62 years, range from 35 to 86, followed-up for MTC were included in the present retrospective study. In our patients 64 18F-DOPA scans, 28 neck US, 28 CT and 8 MRI were performed. For all cases basal calcitonin values were available. Sensitivity and specificity of 18F-DOPA PET and conventional imaging (US, CT, MRI) related to calcitonin values were calculated., Results: According to the calcitonin cut-off of 150 pg/ml, we found the following sensitivities and specificities: 79% and 80% for 18F-DOPA PET, 75% and 92% for US, 80% and 25% for CT, 50% and 75% for MRI. Taking the level of detectable calcitonin, we calculated the following sensitivities: 52% for 18F-DOPA PET, 46% for US, 79% for CT and 38% for MRI., Conclusion: We cannot confirm the calcitonin cut-off proposed by the ATA for the detection of MTC recurrences and contemporaneously we cannot state that 18F-DOPA PET has a very high sensitivity. For the neck region 18F-DOPA PET and US showed similar results. 18F-DOPA PET/CT seems to be the best imaging modality for whole-body tumor detection. Bone metastases are best detected by MRI., (Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Aim: To describe the (18)F-fluorodihydro-xyphenylalanine ((18)F-DOPA), positron emission tomography (PET) and magnetic resonance imaging (MRI) appearance of pheochromocytomas, with a focus on the presence or absence of typical MRI features., Materials and Methods: Eleven patients with histologically-verified pheochromocytoma [sporadic (n=9), multiple endocrine neoplasia (MEN) 2A syndrome (n=2)] were enrolled retrospectively. All patients underwent an MRI examination of the upper abdomen. Nine out of 11 patients underwent (18)F-DOPA PET/CT, and the remaining two patients underwent independent PET and computed tomography (CT) examinations. (18)F-DOPA-PET/CT examinations were considered positive when an increased tracer accumulation in the adrenal region, as shown on CT images, was observed. When an adrenal mass was detected on MRI, the T1 and T2 signal intensity and contrast enhancement pattern were recorded. Based on MR characteristics, the lesions were divided into typical and atypical., Results: Ten out of 11 patients had one lesion, while one patient had two lesions. All pheochromocytomas were detected by both PET/CT and MRI. On (18)F-DOPA scans, all lesions showed an increased tracer accumulation, with a mean maximum standardized uptake value (SUVmax) of 13.7±5.75. Eight out of 12 pheochromocytomas exhibited typical MRI features, with intermediate signal intensity on T1-weighted images in-phase, absence of signal drop on T1-weighted images out-of-phase, high signal intensity on T2-weighted images, and clear contrast enhancement in the arterial phase. The remaining four lesions exhibited atypical MRI features, namely absence of one of the listed criteria., Conclusion: In the assessment of pheochromocytoma, the combination of (18)F-DOPA PET with MRI is superior to MRI-alone. (18)F-DOPA PET/MRI may yield a higher diagnostic confidence for the detection of pheochromocytoma than (18)F-DOPA PET/CT.

Purpose: To assess the influence of reconstruction algorithms for positron emission tomography (PET) based volume quantification. The specifically detected activity in the threshold defined volume was investigated for different reconstruction algorithms as a function of volume size and signal to background ratio (SBR), especially for volumes smaller than 1ml. Special attention was given to the Siemens specific iterative reconstruction algorithm TrueX., Methods: Measurements were performed with a modified in-house produced IEC body phantom on a Siemens Biograph 64 True Point PET/CT scanner (Siemens, Medical Systems) for six different SBRs (2.1, 3.8, 4.9, 6.7, 8.9, 9.4 and without active background (BG)). The phantom consisted of a water-filled cavity with built-in plastic spheres (0.27, 0.52, 1.15, 2.57, 5.58 and 11.49ml). The following reconstruction algorithms available on the Siemens Syngo workstation were evaluated: Iterative OSEM (OSEM) (4 iterations, 21 subsets), iterative TrueX (TrueX) (4 iterations, 21 subsets) and filtered backprojection (FBP). For the threshold based volume segmentation the software Rover (ABX, Dresden) was used., Results: For spheres larger than 2.5ml a constant threshold (standard deviation (SD) 10%) level was found for a given SBR and reconstruction algorithm and therefore a mean threshold for the largest three spheres was calculated. This threshold could be approximated by a function inversely proportional to the SBR. The threshold decreased with increasing SBR for all sphere sizes. For the OSEM algorithm the threshold for small spheres with 0.27, 0.52 and 1.15ml varied between 17% and 44% (depending on sphere size). The threshold for the TrueX algorithm was substantially lower (up to 17%) than for the OSEM algorithm for all sphere sizes. The maximum activity in a specific volume yielded the true activity for the OSEM algorithm when using a SBR independent correction factor C, which depended on sphere size. For the largest three volumes a constant factor C=1.10±0.03 was found. For smaller volumes, C increased exponentially due to the partial volume effect. For the TrueX algorithm the maximum activity overestimated the true activity., Conclusion: The threshold values for PET based target volume segmentation increased with increasing sphere size for all tested algorithms. True activity values of spheres in the phantom could be extracted using experimentally determined correction factors C. The TrueX algorithm has to be used carefully for quantitative comparison (e.g. follow-up) and multicenter studies., (Copyright © 2010. Published by Elsevier GmbH.)

Peptide receptor radionuclide therapy (PRRT) has recently been established as an important treatment modality for somatostatin receptor (SSTR)-positive tumors. The purpose of this study was to evaluate the clinical response, side-effects as well as the quality of life following (90)Y-DOTA-lanreotide (DOTALAN) and/or (90)Y-DOTA-Tyr (3)-DPhe(1)-octreotide (DOTATOC) therapy in patients with progressive metastatic disease during a 6-year follow-up period. Following dosimetric evaluation with (111)In-DOTALAN and (111)In-DOTATOC, 13 patients with estimated absorbed tumor doses of >5 Gy/GBq (carcinoid, n = 5; radioiodine-negative thyroid cancer, n = 4; gastrinoma, n = 1; insulinoma, n = 1; glucagonoma, n = 1; glomus jugularis tumor, n = 1) were assigned for PRRT. A dose of 925 MBq of (90)Y-DOTALAN (four patients) or 1.85-3.7 GBq of (90)Y-DOTATOC (10 patients) was administered intravenously and repeated every 4-8 weeks. Tumor dosimetry was performed prior to and under therapy, re-staging every 2-3 months. Pain intensity, Karnofsky score and general symptoms were evaluated in order to determine quality of life. Patients were followed until death. Altogether, 53 infusions of PRRT (1.85-14.1 GBq) were administered. After the first follow-up of 3 months of (90)Y-DOTALAN therapy, stable disease (SD) was observed in one patient and progressive disease (PD) in three patients. With (90)Y-DOTATOC therapy, SD was found in all 10 patients. During the re-evaluation period (4-27 months), one patient had to be shifted from (90)Y-DOTALAN to (90)Y-DOTATOC therapy due to reduced (111)In-DOTALAN uptake after 5.5 GBq. In the first 6 months after PRRT with DOTATOC, SD was found in nine of 10 patients and PD in one patient. Thereafter, SD was observed in two patients and PD in eight patients. Nine of 13 patients after PRRT with either DOTALAN or DOTATOC died. None of the patients had experienced severe acute hematological side-effects. Transient thrombocytopenia or lymphocytopenia was seen in 10 patients after 3.7 GBq, and a skin reaction in one patient. Total accumulated kidney dose ranged between 4 and 64 Gy, with reduced creatinine clearance in two patients. Pain relief was achieved in three of three patients after ~3.7 GBq ERT within 4-6 months. Appetite, weight, Karnofsky score and general well-being had improved in patients with SD during and after therapy. Based on the results of this study conducted on a small group of patients, we conclude that PRRT may offer an alternative treatment option for SSTR-positive tumors, with only mild transient side-effects and a marked improvement in the quality of life.

Purpose and Methods: Regional overexpression of the multidrug transporter P-glycoprotein (P-gp) in epileptic brain tissue may lower target site concentrations of antiepileptic drugs and thus contribute to pharmacoresistance in epilepsy. We used the P-gp substrate R-[(11)C]verapamil and positron emission tomography (PET) to test for differences in P-gp activity between epileptogenic and nonepileptogenic brain regions of patients with drug-resistant unilateral temporal lobe epilepsy (n = 7). We compared R-[(11)C]verapamil kinetics in homologous brain volumes of interest (VOIs) located ipsilateral and contralateral to the seizure focus., Results: Among different VOIs, radioactivity was highest in the choroid plexus. The hippocampal VOI could not be used for data analysis because it was contaminated by spill-in of radioactivity from the adjacent choroid plexus. In several other temporal lobe regions that are known to be involved in seizure generation and propagation ipsilateral influx rate constants K(1) and efflux rate constants k(2) of R-[(11)C]verapamil were descriptively increased as compared to the contralateral side. Parameter asymmetries were most prominent in parahippocampal and ambient gyrus (K(1), range: -3.8% to +22.3%; k(2), range: -2.3% to +43.9%), amygdala (K(1), range: -20.6% to +31.3%; k(2), range: -18.0% to +38.9%), medial anterior temporal lobe (K(1), range: -8.3% to +14.5%; k(2), range: -14.5% to +31.0%) and lateral anterior temporal lobe (K(1), range: -20.7% to +16.8%; k(2), range: -24.4% to +22.6%). In contrast to temporal lobe VOIs, asymmetries were minimal in a region presumably not involved in epileptogenesis located outside the temporal lobe (superior parietal gyrus, K(1), range: -3.7% to +4.5%; k(2), range: -4.2% to +5.8%). In 5 of 7 patients, ipsilateral efflux (k(2)) increases were more pronounced than ipsilateral influx (K(1)) increases, which resulted in ipsilateral reductions (10%-26%) of R-[(11)C]verapamil distribution volumes (DV). However, for none of the examined brain regions, any of the differences in K(1), k(2) and DV between the epileptogenic and the nonepileptogenic hemisphere reached statistical significance (p > 0.05, Wilcoxon matched pairs test)., Conclusions: Even though we failed to detect statistically significant differences in R-[(11)C]verapamil model parameters between epileptogenic and nonepileptogenic brain regions, it cannot be excluded from our pilot data in a small sample size of patients that regionally enhanced P-gp activity might contribute to drug resistance in some patients with temporal lobe epilepsy.

[123I]ADAM (2-((2-((dimethylamino)methyl)phenyl)thio)-5-iodophenylamine) is a promising radioligand for in-vivo quantification of serotonin transporters (SERT) using single photon emission computed tomography (SPECT) in man. We performed tracer kinetic analysis in various brain regions to determine the optimum equilibrium time for SERT quantification with [123I]ADAM and SPECT. Radiosyntheses of [123I]ADAM were performed at MAP Medical Technologies Oy, Tikkakoski, Finland. Thirty healthy male volunteers (21-41 yr) received between 104 and 163 MBq [123I]ADAM intravenously as a bolus. Consecutively, multiple SPECT scans were performed between 14 and 420 min post-injection (p.i.) using a Siemens Multispect 3 camera. Reconstruction was performed applying filtered back projection with a Butterworth filter (cut-off 0.7, order 7) in 128x128 matrices. Regions of interest (ROI) were drawn manually on the individual T1-weighted magnetic resonance image (MRI) comprising midbrain/hypothalamus for specific binding to SERT, and the cerebellum as reference region. After re-orientation to the MRI, the ROI template was applied to SPECT studies. We generated time-activity curves for the ROI and calculated the ratio countstarget/countscerebellum minus 1 (=V3'') as a measure for specific SERT binding. Counts were corrected for applied activity, acquisition time and body-weight. Peak uptakes were observed between 14 and 50 min after bolus injection. Counts per voxel were highest in the midbrain/hypothalamus, 798 (max. 872, min. 728), whereas 462 counts per voxel (max. 599, min. 412) were measured in the cerebellum at a mean time of 31 min p.i. Stable values for V3'' reached 205-320 min p.i. Mean peak V3'' value was 1.43 (95% CI 171-230) for the midbrain/hypothalamus at 205 min p.i. [123I]ADAM is a useful ligand for in-vivo quantification of human SERT by means of SPECT, with a comparatively better signal-to-noise ratio compared to beta-CIT. Our data suggest that the acquisition time for the SPECT scan is optimally, under pseudo-equilibrium conditions, between 205-320 min post-bolus injection of the tracer.

The aim of the study was to evaluate the possible changes in CD4+ and CD8+ T-cell cytokine production patterns in Hashimoto's thyroiditis (HT) with elevated calcitonin (CT). Fourteen consecutive patients with verified HT were included in the present study. Patients were divided into two groups. Group I: 7 HT patients with elevated CT levels (>10 pg/ml); Group II: 7 HT patients with CT levels <10 pg/ml). All patients underwent intracellular cytokine detection in CD4+ and CD8+ T-cells of peripheral blood mononuclear cells (PBMC) by flow cytometry. Patients with elevated CT levels (group I) had significantly higher percentages of CD8+ cells producing IFN-gamma compared to healthy donors. A detailed analysis of cytokine production patterns revealed that this was accompanied by an increased frequency of single IFN-gamma positive cells, i.e., cells not expressing most of the other cytokines tested. Similarly, patients in group I also showed higher percentages of CD8+ TNF-alpha positive cells than healthy donors. In this case, cells co-expressing TNF-alpha and IFN-gamma were found at significantly higher frequencies. No increase in Th1 type cytokines, such as IFN-gamma or TNF-alpha, was detectable in CD4+ T-cells. In contrast, CD4+ T-cells from group I patients showed significantly higher percentages of cells producing Th2 cytokines, such as IL-4 or IL-13. The lack of increased Th1 cytokine production accompanied by an increased Th2 cytokine production seems to be a special feature of HT patients with elevated CT levels that may reflect a pathogenetic mechanism for tumor initiation.

The measurement of basal serum calcitonin (CT) in patients with evidence of Hashimoto's thyroiditis (HT) has been proposed in a recent study demonstrating an increased prevalence of elevated basal and stimulated CT. The aim of this study was to evaluate the frequency and relevance of elevated CT levels in HT. The basal sera CT were measured in 568 consecutive HT patients using a chemiluminescent immuno-assay. Whenever the serum CT was > 10 pg/ml, a pentagastrin (PG) stimulation test was performed. Two patients with abnormal/pathological PG tests were identified. Total thyroidectomy and lymph node dissection revealed for the first patient medullary thyroid carcinoma (MTC) and for the second patient C cell hyperplasia (CCH), together with papillary thyroid carcinoma. Our data showed a low prevalence of MTC and its premalignant condition CCH in HT patients; nevertheless, the patient with MTC presented lymph node metastasis. The fact that both cases presented without evidence of nodular thyroid disease highlights the persistent diagnostic dilemma of CT screening programs.

Background: Mesalazine (5-aminosalicylic acid, 5-ASA) containing formulations represent a cornerstone in the treatment of inflammatory bowel diseases. A novel formulation with an Eudragit L/S mixture coating has been developed to provide selective release of 5-ASA to the ileo-caecal region and the colon., Aim: To determine the release of 5-ASA during the gastrointestinal transit., Methods: A single oral dose of mesalazine EC 500 mg gastroresistant tablets (Asamax) was administered to eight healthy male volunteers. Gastrointestinal transit and tablet disintegration were monitored by scintigraphy. 5-ASA release was verified by assessing plasma pharmacokinetics., Results: Initial tablet disintegration was observed 5.65 +/- 0.86 h after dosing, corresponding to the detection of 5-ASA in plasma. This occurred in the ileo-caecal region in three subjects and the ascending colon in the remaining five. The relative percentage of 5-ASA absorption was more pronounced in the ascending colon (41 +/- 27.4%) than the ileo-caecal region (6.6 +/- 9.2%)., Conclusion: This mesalazine EC gastroresistant tablets release locally active 5-ASA specifically in the ileo-caecal region and the ascending colon.

Aims: The aims of the study were to: (1) evaluate the gastrointestinal transit, release and absorption of budesonide from tablets with a new multimatrix formulation (MMX) designed to release the drug throughout the whole colon, and (2) assess the influence of food on budesonide bioavailability., Methods: Two phase I studies, each comprising 12 healthy males, were performed. Gastrointestinal transit of (153)Sm-labelled tablets containing 9 mg budesonide was evaluated by means of pharmaco-scintigraphy. The effect of food was tested by comparing plasma pharmacokinetics after intake of a high fat and high calorie breakfast with fasting controls., Results: (153)Sm-labelled tablets reached the ascending colon after a mean +/- SD 9.8 +/- 6.9 h. Initial tablet disintegration was observed in the ileum in 42% and the ascending and transverse colon in 33% of subjects. Ninety-six per cent of the dose was absorbed into the systemic circulation during passage through the whole colon including the sigmoid. Food significantly decreased C(max) values from 1429 +/- 1014 to 1040 +/- 601 pg mL(-1) (P = 0.028) and AUC values from 14 814 +/- 11 254 to 13 486 +/- 9369 pg h(-1) mL(-1) (P = 0.008). Mean residence time and t(max) increased by 12-29%. There was no drug accumulation after 1 week of once daily oral administration of budesomide., Conclusions: MMX-budesonide tablets appear suitable for targeted colonic drug delivery. Transit parameters and low systemic bioavailability warrant further studies with the new formulation.

Unlabelled: Because many drugs possess an intracellular site of action, the knowledge of intracellular concentration-time profiles is desirable. In the present study, PET, which measures total (i.e., intracellular, extracellular, and intravascular) concentrations of radiolabeled drugs in tissue, and microdialysis, which determines unbound drug concentrations in the extracellular space fluid of tissue, were combined to describe the intracellular pharmacokinetics of a model compound--that is, the (18)F-labeled antibiotic (18)F-ciprofloxacin--in vivo in humans., Methods: Ten healthy male volunteers received a mixture of 687 +/- 50 MBq of (18)F-ciprofloxacin and 200 mg of unlabeled ciprofloxacin as an intravenous bolus infusion over 10 min. The pharmacokinetics of ciprofloxacin in skeletal muscle tissue were assessed by means of combined PET and in vivo microdialysis for 5 h after drug administration. A 3-compartment pharmacokinetic model was fitted to the tissue concentration-time profiles of ciprofloxacin measured by PET to estimate the rate constants of ciprofloxacin uptake and transport., Results: In muscle tissue, mean total and extracellular peak concentration (C(max)) values of ciprofloxacin of 1.8 +/- 0.4 microg/mL and 0.7 +/- 0.2 microg/mL were attained at 95 +/- 34 min and 48 +/- 20 min after drug administration, respectively. The extracellular-to-intracellular exchange appeared to be very fast, with an estimated rate constant k(3) of 1.69 +/- 0.25 min(-1). An intracellular-to-extracellular concentration ratio (C(intra)/C(extra)) of 3.2 +/- 0.8 was reached at 110 min after injection and followed by sustained intracellular retention of the antibiotic for the remainder of the experiment. The predicted extracellular concentration-time profiles from the compartmental modeling were in good agreement with the measured microdialysis data., Conclusion: The results obtained in the present study were in accordance with previous in vitro data describing cellular ciprofloxacin uptake and retention. The presently used PET/microdialysis combination might be useful during research and development of new drugs, for which knowledge of intracellular concentrations is of interest.

Background: Local treatment with foams in patients suffering from ulcerative proctitis or proctosigmoiditis is considered a rational treatment option., Aims: To investigate colonic spread, safety, tolerability and acceptance of a newly developed budesonide foam formulation., Methods: Twelve patients (four females, eight males) with acute proctosigmoiditis or left-sided ulcerative colitis were rectally administered a single dose of [99Tcm]-labelled budesonide foam (Budenofalk; Dr Falk Pharma GmbH, Freiburg, Germany) containing 2 mg budesonide in 20 mL foam after diagnostic colonoscopy. Thereafter, the colonic spread was assessed by means of gamma-scintigraphy for 6 h. Serum samples were taken simultaneously., Results: Budesonide foam spread with a maximum between 11 and 40 cm, thus reaching the sigmoid colon in all patients. In some patients, the foam even extended into the distal third and the middle of the descending colon with maximum radioactivity at 4 h. Systemic budesonide absorption was rapid and pharmacokinetic data were comparable with published data on marketed budesonide enemas, with mean serum C(max) and AUC(0-8 h) values of 0.8 +/- 0.5 ng/mL and 3.7 +/- 1.9 ng h/mL, respectively. The new formulation was well accepted by all patients, who could retain the foam for at least 4 h., Conclusions: In the majority of patients, budesonide foam effectively spread up to the left-sided colon and thus qualifies for the local treatment of proctosigmoiditis.

Unlabelled: The aim of this study was to compare nonfluoroscopic electroanatomic mapping (NOGA), SPECT perfusion imaging, and PET metabolic imaging for assessment of myocardial viability. In particular, we sought to elucidate differences of electromechanical properties between the perfusion/metabolism mismatch as an indicator of a potentially reversible ischemic injury and the perfusion/metabolism match indicating irreversibly damaged myocardial tissue., Methods: Twenty-one patients with coronary artery disease underwent NOGA mapping of endocardial unipolar voltage, cardiac 18F-FDG PET of glucose utilization, and resting 201Tl SPECT of myocardial perfusion., Results: Electrical activity was 10.8 +/- 4.6 mV (mean +/- SD) in normal myocardium and was unchanged in hypoperfused segments with maintained glucose metabolism (perfusion/metabolism mismatch), 9.3 +/- 3.4 mV (P = not significant). In contrast, hypoperfused segments with a perfusion/metabolism match and nonviable segments showed significantly lower voltage (6.9 +/- 3.1 mV, P < 0.0001 and 4.1 +/- 1.1 mV, P < 0.0001 vs. normal). In hypoperfused segments, metabolic activity was more closely related to endocardial voltage than was myocardial perfusion (201Tl vs. voltage: r = 0.38, SEE = 3.2, P < 0.001; 18F-FDG PET vs. voltage: r = 0.6, SEE = 2.8, P < 0.0001)., Conclusion: In hypoperfused myocardium, electrical activity by NOGA mapping is more closely related to PET metabolic activity than to SPECT myocardial perfusion. As NOGA mapping does not differentiate hypoperfused myocardium with enhanced glucose utilization from normal myocardium, results from NOGA mapping need to be correlated with results from perfusion imaging to identify hypoperfused, yet viable, myocardium and to stratify patients for revascularization procedures.

The biodistribution and pharmacokinetics of the fluorine-18-labeled fluoroquinolone antibiotic [(18)F]ciprofloxacin in tissue were studied noninvasively in humans by means of positron emission tomography (PET). Special attention was paid to characterizing the distribution of [(18)F]ciprofloxacin to select target tissues. Healthy volunteers (n = 12) were orally pretreated for 5 days with therapeutic doses of unlabeled ciprofloxacin. On day 6, subjects received a tracer dose (mean injected amount, 700 +/- 55 MBq, which contained about 0.6 mg of unlabeled ciprofloxacin) of [(18)F]ciprofloxacin as an intravenous bolus. Thereafter, PET imaging and venous blood sampling were initiated. Time-radioactivity curves were measured for liver, kidney, lung, heart, spleen, skeletal muscle, and brain tissues for up to 6 h after radiotracer administration. The first application of [(18)F]ciprofloxacin in humans has demonstrated the safety and utility of the newly developed radiotracer for pharmacokinetic PET imaging of the tissue ciprofloxacin distribution. Two different tissue compartments of radiotracer distribution could be identified. The first compartment including the kidney, heart, and spleen, from which the radiotracer was washed out relatively quickly (half-lives [t(1/2)s], 68, 57, and 106 min, respectively). The second compartment comprised liver, muscle, and lung tissue, which displayed prolonged radiotracer retention (t(1/2), >130 min). The highest concentrations of radioactivity were measured in the liver and kidney, the main organs of excretion (standardized uptake values [SUVs], 4.9 +/- 1.0 and 9.9 +/- 4.4, respectively). The brain radioactivity concentrations were very low (<1 kBq. g(-1)) and could therefore not be quantified. Transformation of SUVs into absolute concentrations (in micrograms per milliliter) allowed us to relate the concentrations at the target site to the susceptibilities of bacterial pathogens. In this way, the frequent use of ciprofloxacin for the treatment of a variety of infections could be corroborated.

Unlabelled: Nuclear medicine plays an important role in the imaging of neuroendocrine tumors (NETs). Somatostatin receptor scintigraphy (SRS) with (111)In-labeled somatostatin receptor analogs is a standard procedure for the detection and staging of NET. Based on the ability of NETs to store biogenic amines, this study evaluated whether 6-(18)F-fluoro-L-DOPA ((18)F-FDOPA) is a suitable PET tracer for NETs., Methods: Twenty-three patients with histologically verified NETs in advanced stages were consecutively enrolled in the study. All patients underwent PET with (18)F-FDOPA, CT, and SRS within 6 wk. In patients with discrepancies between nuclear medicine and radiologic methods, follow-up investigations were performed by CT, MRI, and ultrasound. (18)F-FDOPA PET with attenuation correction was done 30 and 90 min after injection from the neck to the upper legs. SRS was performed with (111)In-DOTA-D-Phe(1)-Tyr(3)-octreotide at 6 and 24 h. All images were read without knowledge of the results of the other modalities. In every patient, the following regions were evaluated separately: bones, mediastinum, lungs, liver, pancreas, and others, including the abdominal and supraclavicular lymph nodes, spleen, and soft- tissue lesions. The findings were confirmed by clinical examination. The nuclear medicine methods were compared against morphologic imaging, which was considered as gold standard., Results: The most frequently involved organs or regions were the liver (prevalence, 70%) and bone (52%), followed by mediastinal foci (31%), the lungs (22%), and the pancreas (13%). Fifty-two percent of patients had various lymphatic lesions. (18)F-FDOPA was most accurate in detecting skeletal lesions (sensitivity, 100%; specificity, 91%) but was insufficient in the lung (sensitivity, 20%; specificity, 94%); SRS yielded its best results in the liver (sensitivity, 75%; specificity, 100%); however, it was less accurate than PET in all organs. In about 40%, initial CT failed to detect bone metastases shown by PET that were later on verified by radiologic follow-up., Conclusion: (18)F-FDOPA PET performs better than SRS in visualizing NETs and may even do better than CT for bone lesions. SRS is essential to establish the usefulness of therapy with somatostatin analogs, yet is less accurate than (18)F-FDOPA PET for staging.

Unlabelled: This study presents and evaluates a model-based image analysis method to calculate from gated cardiac (18)F-FDG PET images diastolic and systolic volumes, ejection fraction, and myocardial mass of the left ventricle. The accuracy of these estimates was delineated using measurements obtained by MRI, which was considered the reference standard because of its high spatial resolution., Methods: Twenty patients (18 men, 2 women; mean age +/- SD, 59 +/- 12 y) underwent electrocardiography-gated cardiac PET and MRI to acquire a set of systolic and diastolic short-axis images covering the heart from apex to base. For PET images, left ventricular radius and wall thickness were estimated by model-based nonlinear regression analysis applied to the observed tracer concentration along radial rays. Endocardial and epicardial contours were derived from these estimates, and left ventricular volumes, ejection fraction, and myocardial mass were calculated. For MR images, an expert manually drew contours., Results: Left ventricular volumes by PET and MRI were 101 +/- 60 mL and 112 +/- 93 mL, respectively, for end-systolic volume and 170 +/- 68 mL and 189 +/- 99 mL, respectively, for end-diastolic volume. Ejection fraction was 44% +/- 13% by PET and 46% +/- 18% by MRI. The left ventricular mass by PET and MRI was 196 +/- 44 g and 200 +/- 46 g, respectively. PET and MRI measurements were not statistically significant. A significant correlation was observed between PET and MRI for calculation of end-systolic volumes (r = 0.93, SEE = 23.4, P < 0.0001), end-diastolic volumes (r = 0.92, SEE = 26.7, P < 0.0001), ejection fraction (r = 0.85, SEE = 7.4, P < 0.0001), and left ventricular mass (r = 0.75, SEE = 29.6, P < 0.001)., Conclusion: Model-based analysis of gated cardiac PET images permits an accurate assessment of left ventricular volumes, ejection fraction, and myocardial mass. Cardiac PET may thus offer a near-simultaneous assessment of myocardial perfusion, metabolism, and contractile function.

Background: Recent studies have shown that vascular endothelial growth factor (VEGF) receptor is overexpressed in vascular endothelial cells of various human tumours as well as in human tumour cells. The aim of this study was to evaluate the usefulness of scanning with VEGF(165) labeled with (123)I for tumor localisation in patients with gastrointestinal tumours., Patients and Methods: Human recombinant VEGF(165) was radiolabelled with (123)I by electrophilic radioiodination using the chloramine T method. [(123)I]VEGF(165) was administered intravenously [mean dose 184 +/- 18 MBq (

An increased prevalence of autoimmune thyroiditis (AT) in vitiligo patients is well known. The aim of this study was firstly, to evaluate the clinical course of patients with both vitiligo and AT and secondly, to identify additional autoimmune disorders affecting the thyroid gland in a large cohort of vitiligo patients. We analysed a study group of 106 vitiligo patients and 38 controls. A detailed thyroid examination including sonography was performed in all study participants. In addition, the study participants were HLA typed and screened for various autoimmune disorders. AT was significantly more frequent in vitiligo patients than in controls (21%versus 3%; P < 0.01). In 12 of the 22 patients with AT, vitiligo was the initial disease preceding AT by 4-35 years. In the other 10 patients with AT, both vitiligo and AT were diagnosed within one year. There were two individuals with diabetes mellitus type 1 and a single patient with Addison's disease. Anti-nuclear antibody (ANA), anti-smooth muscle cell antibody, and parietal cell antibody levels occurred with a similar frequency in patients and controls. In all vitiligo patients with both elevated ANA levels and AT (n = 6), the atrophic but not the goitrous variant was diagnosed. These vitiligo patients with both AT and elevated ANA levels had a significantly smaller thyroid volume compared to the vitiligo patients with AT whose ANA levels were normal (6.7 +/- 4.5 ml versus 13.4 +/- 9.1 ml, respectively; P < 0.05). The same was found in the entire study group: Thyroid volume of all vitiligo patients (with or without concomitant AT) was significantly smaller in the presence of ANA (6.9 +/- 5.3 versus 10.5 +/- 5.9 ml, respectively; P < 0.05). However, this phenomenon was not observed in the control group. There was a trend for a decreased frequency of HLA-DR3 (6.7%versus 23%) in our study group, but after correction for the number of comparisons, no HLA-allele was statistically significant associated neither with vitiligo nor with multiple autoimmune diseases in our patient sample. Our findings suggest that AT is the most frequent autoimmune disease associated with vitiligo. In our patients, AT presented simultaneously or after the onset of vitiligo but not before. Elevated ANA levels were associated with the atrophic variant of AT and may affect the volume of the thyroid gland, and there was no statistically significant association with the HLA system.

We have determined the predictive value of [18F]2-fluoro-2-deoxy-glucose (FDG-PET) in patients with Hodgkin's disease (HD) and aggressive non-Hodgkin's lymphoma (NHL) scheduled for high-dose therapy with stem cell transplantation (HDT/SCT). Inclusion criteria were the presence of an FDG-PET scan after chemotherapy (ChT) within 8 weeks prior to HDT/SCT and available follow-up data. Sixteen patients (10 NHL and six HD) were observed during a follow-up period of 4 to 28 months (median 13 months). Before SCT, five patients had a negative PET, three were weakly positive, two moderately positive, and six strongly positive. None of the five patients with a negative PET before HDT/SCT relapsed and two of three patients with a weakly positive scan are still in remission after HDT/SCT. Of eight patients with a moderate or high positive PET before HDT/SCT, seven relapsed and one died of early HDT/SCT related complications (P< 0.01). Three of eight relapsing patients died of lymphoma 5 to 10 months after SCT and in one additional patient not responding to HDT/SCT, the main cause of death was chronic toxicity 4 months after transplantation. After 12 months, in PET-negative patients the overall and relapse-free survival was 100%, in PET-positive patients 55% and 18%, respectively. In NHL, two patients with negative PET, but with an age-adjusted international prognostic index (AaIPI) of 2 and one with AaIPI = 1 are still in remission. In the seven PET-positive subjects, one patient with AaIPI = 0, three with AaIPI = 1, and two with AaIPI = 2 relapsed. We conclude that FDG-PET is accurate in the prediction of relapse prior to HDT/SCT in patients with lymphoma. It provides additional information when compared with the AaIPI.

Unlabelled: Specific tumors express high amounts of receptors for somatostatin (SST), providing the basis for imaging and treatment using radiolabeled SST analogs. However, little is known about the potential influence of cytotoxic drugs on SST receptor (SSTR) expression in malignant cells., Methods: To study the interaction between cytotoxic drugs and SSTR expression, the pancreatic cancer-derived tumor cell lines BxPC-3, Panc-1, Capan-1, and ASPC-1 were exposed to a range of cytotoxic drugs in vitro: Gemcitabine, 5-fluorouracil, cisplatin (cis-diaminedichloroplatinum [II]), camptothecin, mitomycin C, and doxorubicin were checked for changes in binding characteristics of the SSTR ligand (111)In-1,4,7,10-tetraazacyclododecane- N,N',N",N"'-tetraacetic acid-lanreotide (DOTA-LAN). Chemosensitivity was quantitated by measurements of reduction in cell numbers, changes in cell cycle distribution, and appearance of apoptotic subG1 (subG1/0 cell DNA content) cells., Results: Cells were treated with gemcitabine (1.0 or 2.0 microg/mL), 5-fluorouracil (65-520 microg/mL), camptothecin (1.5 or 3 microg/mL), mitomycin C (0.1 or 0.2 microg/mL), and doxorubicin (1.0 or 2.0 microg/mL). Each of the chemotherapeutic agents induced a loss of high-affinity receptors. In addition, gemcitabine caused a reduction of low-affinity receptors in BxPC-3, Panc-1, and ASPC-1 cells. Mitomycin C, camptothecin, and 5-fluorouracil also induced an overexpression of low-affinity receptors. In cells pretreated with cisplatin (2-10 microg/mL), binding of DOTA-LAN was increased. Excluding gemcitabine, the increase in low-affinity binding sites exhibits a weak correlation with apoptosis (r(2) = 0.62). For gemcitabine, these effects were reversed after 4 d of recovery of the cell lines, eventually revealing overexpression of low- and high-affinity sites for BxPC-3 and Panc-1 cells and low-affinity sites for ASPC-1 cells., Conclusion: Our results clearly show that the pancreatic tumor lines reduce the expression of high-affinity DOTA-LAN binding sites during application of chemotherapeutic drugs, which is accompanied by variable overexpression of low-affinity binding sites. In the case of gemcitabine, SSTRs are overexpressed during recovery from drug exposure within 4 d. These findings may have implications on the interpretation of scintigraphic results obtained by receptor ligands.

Unlabelled: Imaging with radiolabeled somatostatin (SST) analogs has recently been established for the localization of various human SST receptor (hsstr)-positive tumors, including neuroendocrine tumors, lymphomas, and non-small cell lung cancer (NSCLC)., Methods: 111In-1,4,7,10-tetraazacyclododecane-N,N',N",N"'-tetraacetic acid-lanreotide (DOTA-LAN) scintigraphy (150 MBq; 7 nmol per patient) was performed on 47 patients (28 patients with primary tumors, 19 patients with lung metastases from other tumors) to evaluate the tumor binding in patients with histologically confirmed lung cancer. A group of 27 tumor patients without documented lung lesions served as the control group. Early and delayed planar and SPECT images were acquired. Whole-body scintigraphy was performed at 0.5, 4-6, 24, and 48 h after injection for tumor dose estimation. In addition, hsstr subtype expression and radioligand binding characteristics were studied in vitro using lung tumor samples (n = 15)., Results: 111In-DOTA-LAN indicated the primary lung tumor in 16 of 16 NSCLC patients. Lymph node metastases were visualized in 6 of 6 NSCLC patients, and bone metastases were seen in 3 of 3 NSCLC patients. 111In-DOTA-LAN scintigraphy indicated lung carcinoid in 5 of 5 patients and small cell lung cancer lesions in 6 of 6 patients. Multiple lung metastases were shown in all 6 patients with non-Hodgkin's lymphoma and in the 1 patient with Hodgkin's disease, 5 of 5 colorectal adenocarcinoma patients, 4 of 4 carcinoid patients, 2 of 2 neuroendocrine carcinoma (NEC) patients, and 1 of 1 angiosarcoma patient. Pulmonary tumor sites not indicated by CT or MRI were visualized in 6 of 47 tumor patients (i.e., 13%; lung metastases in 1 carcinoid patient and 1 NEC patient, lymph node metastases in 1 carcinoid patient and 2 NSCLC patients, bone metastases in 1 carcinoid patient). The estimated lung tumor dose ranged between 0.2 and 5 mGy/MBq. Focal lung uptake of 111In-DOTA-LAN was not observed in any of the 27 control patients. In vitro binding studies indicated high-affinity binding sites for 111In-DOTA-LAN in NSCLC samples (dissociation constants, 0.5 and 4 nmol/L) with predominant expression of hsstr4., Conclusion: 111In-DOTA-LAN yields high tumor binding for various human lung tumors. Consecutively, radiopeptide therapy may offer a potential new treatment alternative for some lung tumor patients.

Purpose. Tc-99m tetrofosmin launched for myocardial studies has recently also shown a good detectability for several tumors. Data on PNET imaging by Tc-99m tetrofosmin are not yet available.Patient and method. In the case of a 21-year-old man suffering from pelvis PNET, Tc-99m tetrofosmin scintigraphy was performed additionally to CT and MRI.Results. The gluteal and iliac tumor masses were visualized by Tc-99m tetrofosmin according to the CT and MRI results.Discussion. Imaging with Tc-99m tetrofosmin could provide additional information to the available conventional radiological imaging modalities for diagnosis of PNET, and could be a useful tool for the restaging of the primary tumor.

Background: Based on the high number of somatostatin (SST) receptors expressed by neuroendocrine tumors, long-acting SST analogs have been successfully used for tumor detection. New developments point to the potential use of these types of radioligands for tumor-specific radionuclide therapy., Patients and Methods: We have comparatively investigated the diagnostic capacity of the SST analog. 111In-DOTA-lanreotide (LAN), as opposed to 111ln-DOTA-DPhe1-Tyr3-octreotide (TOCT) in tumor patients. This article gives an overview of recent scintigraphic results compared to CT/MRI, 18F-FDG-PET, endoscopy and/or surgery in a threshold of 218 tumor patients., Results: As opposed to radiology, previously unknown tumor lesions were demonstrable by either SST radioligand in about one third of patients. In carcinoid patients, the SST scan sensitivity was 64% for LAN (18 of 28) and 87% (34 of 39) for TOCT, whereas the sensitivity was 100% in patients with (radioiodine-negative) thyroid cancer (17 of 17) for LAN and 95% for TOCT (20 of 21). Discordant scintigraphic results between LAN and TOCT (higher tumor uptake and/or visualisation of different lesions in the same patient) were also seen in patients with lymphoma, lung cancer and intestinal adenocarcinoma. In a direct comparison of both SST tracers in 38 tumor patients, LAN gave positive results in 35 of 38, TOCT in 36 of 38 and 18F-FDG-PET in 14 of 22 of the same patients. SST scan results obtained by both tracers were equivocal in 23 of 38 patients, but were better in 10 patients withTOCTand in 5 patients with LAN., Conclusions: We conclude that both SST radioligands are suitable tracers for tumor imaging, but may give significantly different uptake results for different tumor types. Since the uptake is most important for tumor therapy, using either longacting SSTanalogs, and/or 90Y-labeled analogs, careful evaluation should be made prior to therapy.

The purpose of this study was to investigate the efficacy of the patient-based coronary heart disease (CHD) risk management strategy in general practice by analyzing patients who were sent to a specialized center as refractory to conventional treatment. Of the 452 patients studied, 152 were excluded because of secondary hyperlipidemia. The effects of a food protocol-monitored dietary/drug treatment on lipid profiles and CHD risk indices and the compliance to this approach were monitored for 12 months in 300 of 452 patients. CHD risk classification was performed according to NIH criteria by the referring physicians, but secondary hyperlipidemia was not identified and treated appropriately. Physicians did not fully utilize dietary and drug treatment and referred the patients to a specialized center too early. The initiated food protocol-controlled treatment was more efficient than pretreatment in general practice, with a compliance of 80.3% by patients selected according to their CHD risk. Long-term CHD risk reduction was persistent for 12 months in compliant patients; however, a cumulative dropout rate of 43% after 6 months and of 68% after 12 months was noted. Statistical analysis failed to reveal consistent prognostic factors of long-term compliance.

Purpose: The creation of an endothelial coverage on prosthetic vascular surfaces may improve the performance of synthetic small diameter vascular grafts. In vitro lining with cultured autologous endothelial cells offers a confluent endothelium at the time of implantation., Methods: Between June 1989 and December 1991, 49 patients who had no saphenous vein available entered the study. Indication for operation was disabling claudication in 37 patients and critical ischemia in 12 patients. With a random 1:2 assignment, 33 patients were admitted to the endothelialized group and 16 control patients received an untreated polytetrafluoroethylene prosthesis. Cultured autologous endothelial cells from the external jugular vein were confluently lined onto polytetrafluoroethylene grafts precoated with fibrinolytically inhibited fibrin glue. The follow-up was based on angiography, platelet labeling studies with indium 111-labeled oxine, assessment of the ankle-brachial index, and duplex sonography., Results: First-passage mass cultures of 16 million endothelial cells-required for the confluent lining of a 70 cm long 6 mm graft-were reached 25.1 +/- 11.2 days after vein excision. Growth failure occurred in 27.3%. After 32 months, the actuarial patency was 84.7% for endothelialized grafts and 55.4% for control grafts (p < 0.041 by Breslow test; p < 0.068 by Mantel-Cox test). The ankle-brachial index was continually diverging, reaching significantly lower values in the control group at 24 months (0.98 +/- 0.14 in the endothelialized group versus 0.70 +/- 0.12 in the control; p < 0.0023). The uptake of indium 111-labeled platelets--measured at 9 days, 3 months, 6 months, and 12 months--was significantly lower in the endothelialized group during the entire observation period.

The purpose of this study is to investigate the role of 123I-Tyr-3-octreotide scintigraphy in staging small-cell lung cancer (SCLC), its efficacy for the discrimination of limited and extensive disease stages and its regional sensitivity for different metastatic locations. Twenty patients with histologically confirmed SCLC and 50 radiologically staged tumors sites were investigated by an imaging protocol including dynamic (0-30 min p.i.), static (30 min, 90 min, 4 hr, 24 hr p.i.) and SPECT (90 min p.i.) studies. The primary tumor site was visualized in 84%, whereas the best delineation was noted in early planar (15-30 min p.i.) and SPECT studies, due to a rapidly decreasing tumor-to-background ratio. Lymph node metastases were seen in 73%, but SPECT was needed for anatomical localization. All three adrenal metastases could be identified in sequential planar images. One clinically unsuspected brain metastasis was seen, whereas a second clinically overt metastasis was not visualized. The global and regional sensitivity for liver and bone metastases was unsatisfactory. In summary, 78% (7/9) of the patients with extensive disease were correctly identified by scintigraphy alone. We conclude that 123I-Tyr-3-octreotide scintigraphy is a substantial tool in the staging work-up of SCLC if it is performed initially to allow fast identification of patients with extensive disease stages and save additional radiological or invasive examinations. Yet, 123I-Tyr-3-octreotide scintigraphy cannot substitute liver sonography or conventional bone scanning in patients who have no scintigraphic evidence of distant tumor spread.

Systematic clotting studies were performed in 157 patients with de novo acute nonlymphoblastic leukemia (ANLL) prior to treatment. Sixteen patients had disseminated intravascular coagulation (DIC). Three of the patients with DIC (two with M3, one with M5 leukemia) had a marked isolated factor-X deficiency (factor X:C 21%, 33%, and 41%, respectively). Another four patients had a mild isolated factor-X deficiency (factor X:C 55%-68%). In these seven patients the remaining liver-synthesized clotting factors (factors II, VII, IX, V) as well as serum albumin and cholinesterase were within the normal range. Liver disease or vitamin-K deficiency could therefore be excluded. In none of the 141 patients without DIC was a marked isolated factor X deficiency observed; two patients had moderately reduced factor X:C levels but normal liver-synthesized proteins. Induction treatment led to the control of DIC with an almost parallel increase of fibrinogen and factor X up to normal in all patients with factor-X deficiency who achieved complete remission. In one patient, recurrence of leukemia was associated with reoccurrence of DIC and marked factor-X deficiency. We conclude that there is a coincidence of isolated factor-X deficiency and DIC in some patients with ANLL. In some patients, this factor-X deficiency may be severe enough to contribute to the bleeding tendency.

This study was performed to examine whether cilazapril, a novel nonsulfhydril angiotensin-converting enzyme (ACE) inhibitor, may improve regional myocardial perfusion at exercise in patients with coronary heart disease (CHD). In a single-blind, nonrandomized trial, 5 mg cilazapril or placebo was administered to eight patients with documented CHD and stable exertional angina. Multistage bicycle exercise tests were performed and each patient served as his own control. At peak exercise, as well as at rest, [99mTc]hexakis-2-methoxy-2-isobutylisonitrile myocardial images were obtained. Percent myocardial activity differences (%AD) between exercise and resting images were compared (cilazapril versus placebo). Heart rate and blood pressure were not significantly different between trials. However, after cilazapril administration, %AD was higher than after placebo, with relative differences between trials of greater than 30%, along with alleviation of clinical symptoms in seven of eight patients. These data suggest that in patients with stable-effort angina, ACE inhibition with cilazapril is able to redistribute myocardial blood flow and to improve regional oxygen supply to the ischemic myocardium.

The histories, rest, and exercise ECG results of 60 patients without myocardial infarction complaining of chest pain were submitted to 6 physicians (3 cardiologists and 3 noncardiologists) who were unaware of the angiographic findings. The physicians were requested to estimate the probability of coronary artery disease present in percentages and to assess the need for coronary angiography on a five-point scale (1 = definitely not indicated, 5 = definitely indicated). After obtaining the results of thallium-201 imaging following dipyridamole (0.50 mg/kg intravenously) administration, the physicians were again requested to estimate probability and need for angiography. In the 43 patients with coronary artery disease the judgment of probability was increased significantly after 201Tl from 75.6 +/- 20.2% to 82.9 +/- 23.2% (p less than 0.001) and the need for angiography from 4.3 +/- 0.9% to 4.5 +/- 0.9% (p less than 0.001). In the subgroup of patients with atypical angina the relative change in probability was higher than in other subgroups of patients with coronary artery disease. In the 17 patients with normal coronary arteries the probability estimation fell after 201Tl from 36.7 +/- 22.0% to 24.8 +/- 21.0% (p less than 0.001), the need for angiography was decreased from 2.7 +/- 1.1% to 2.2 +/- 1.2% (p less than 0.001). With the 201Tl information, cardiologists performed a better diagnostic differentiation of patients with and without coronary artery disease than noncardiologists. The study demonstrates the improvement of clinical diagnosis in patients with chest pain by thallium-201 imaging and confirms the favorable influence of the method on the management of the patients in terms of indications for coronary angiography.

Interferon-gamma (IFN-gamma) and tumor necrosis factor (TNF) are lymphokines with a potent hematopoietic progenitor cell suppressive capacity. In untreated and immunosuppressed patients with severe aplastic anemia (SAA) and in control individuals we measured (a) serum levels of IFN-gamma and TNF and its production by peripheral blood mononuclear cells (PBMNC); (b) serum levels of neopterin, a product that reflects endogenous IFN production; (c) resting and activated lymphocyte subpopulations; and (d) serum levels of soluble interleukin-2 receptor (IL-2R). Serum levels of IFN and TNF did not differ significantly in untreated and treated SAA patients and control individuals. Spontaneous and phytohemagglutinin-induced production of IFN and TNF by PBMNC, however, were highly increased in both untreated and treated SAA patients. Increased and decreased neopterin serum levels in untreated and treated SAA patients, respectively, suggest modulation of endogenous lymphokine release subsequent to immunosuppression. HLA-DR+ antigen was mainly expressed by CD8 T cells. Circulating numbers of activated (CD4 and CD8) T cells and serum levels of IL-2R were not increased in both untreated and treated SAA patients. The proportion of HLA-DR+ T cells in the PBMNC of untreated SAA patients correlated with the extent of lectin-induced IFN production. Although we were unable to confirm previous reports in SAA on (a) detectable IFN in blood and bone marrow serum, (b) improvement of stem cell growth upon neutralization of endogenous IFN, (c) absolutely increased numbers of circulating activated T cells, and (d) normalization of these abnormalities subsequent to successful immunosuppression, our data clearly support previous reports on abnormal lymphokine production in severe aplastic anemia. Our failure to relate this phenomenon to the severity of disease states, however, further raises doubts on the pathogenetic significance of lymphokine overproduction in SAA.

Thallium-201 (201Tl) washout analysis was proposed as an adjunctive tool to improve the detection of coronary artery disease (CAD). Since reproducibility of 201Tl washout in dipyridamole (DPM) stress studies is unknown, this item was evaluated in 32 patients (24 with CAD, 8 without CAD), who were scintigraphed twice within 1-2 weeks. At 2 minutes following DPM infusion (0.5 mg/kg/5 min), 2 mCi 201Tl were injected. Global and segmental washout were calculated by comparing circumferential profiles of respective background-corrected stress (left anterior oblique (LAO) 45 degrees: 8 min postinfusion (p.i.), 35 min p.i.; anterior (ANT): 17 min p.i.; LAO 70 degrees: 26 min p.i.) and redistribution (4 h p.i.) images. Whereas visual findings were comparable for study I and II, reproducibility of 201Tl washout was low, indicated by comparing variances among patients with variance between studies, which were 28.8 and 71.2% of total variance, respectively. Mean differences of segmental washout between the studies ranged from 9.75 to 19.24% with only minor differences with regard to the different views and segments evaluated. Variability was lower using the intermediate instead of the initial scintigram as reference for the redistribution image (12.87 +/- 11.64% vs. 18.59 +/- 14.43%, n = 85; p less than 0.01). Variability was higher for nonstenosed compared to stenosed segments (14.54 +/- 11.41%, n = 32 vs. 9.89 +/- 8.03%, n = 28, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Levels of glycosylated hemoglobins (GHb) are significantly (p less than 0.0005) lower in patients with hemolytic anemia (n = 20; mean = 3.9% +/- 0.1% SD GHb of total Hb) compared to patients with nonhemolytic anemia (n = 20; mean = 7.0% +/- 0.7% GHb) and normal controls (n = 30; mean = 6.7% +/- 0.7% GHb). A curvilinear correlation between GHb and red cell survival is demonstrable (n = 20;r2 = 0.88; p less than 0.001). Determination of GHb may be useful as a screening test for hemolytic anemia and for the evaluation of the degree of hemolysis, provided that diabetes mellitus can be excluded.

Ninety-eight female patients (mean age 54 years) who underwent doxorubicin therapy because of metastatic breast cancer were submitted to radionuclide angiography at rest. Left ventricular ejection fractions (LVEFs) were found to decrease significantly with the increasing cumulative doxorubicin dosage. Patients with prior local radiotherapy showed lower LVEFs at the same dosage level than nonirradiated patients, but the difference was not statistically significant. In a further study, 52 patients (mean age 56 years) were followed up regularly for their history and systolic time intervals prior to each doxorubicin treatment course. Before starting treatment, LVEF values were normal in all cases. Fifteen of these patients complained of dyspnea at some time during the treatment period before the critical cumulative dosage level of 550 mg/m2 was reached. Nine of these 15 patients showed an increase of the PEPI:LVETI ratio (greater than or equal to 0.40) and 12 patients a decrease of the LVEF values at rest at the same time. The rest of the patients did not complain of cardiac symptoms and did not show any significant alterations in systolic-time-interval measurements until the borderline dosage level (550 mg/m2) was attained. To evaluate myocardial function with greater accuracy, these 15 patients were submitted to right-heart catheterization and radionuclide angiography at rest and during exercise. As a result, doxorubicin treatment had to be discontinued in three of these patients because of heart failure of stage III or IV and treatment with methyl digoxin and nifedipine was started. In these three patients cardiotonic medication could produce more or less complete cardiac recompensation. We conclude from our findings that signs of stage-III heart failure in radionuclide angiography performed while the patient is at rest and exercising should be regarded as the upper limit of the therapeutic risk, where further doxorubicin treatment is contraindicated. Cardiotonic medication during cytostatic courses should be avoided, however, because the true functional condition of the myocardium could be masked during a potentially cardiotoxic therapy.