Tau filaments are tethered within brain extracellular vesicles in Alzheimer's disease.

The abnormal assembly of tau protein in neurons is the pathological hallmark of multiple neurodegenerative diseases, including Alzheimer's disease (AD). In addition, assembled tau associates with extracellular vesicles (EVs) in the central nervous system of patients with AD, which is linked to its clearance and prion-like propagation between neurons. However, the identities of the assembled tau species and the EVs, as well as how they associate, are not known. Here, we combined quantitative mass spectrometry, cryo-electron tomography and single-particle cryo-electron microscopy to study brain EVs from AD patients. We found filaments of truncated tau enclosed within EVs enriched in endo-lysosomal proteins. We observed multiple filament interactions, including with molecules that tethered filaments to the EV limiting membrane, suggesting selective packaging. Our findings will guide studies into the molecular mechanisms of EV-mediated secretion of assembled tau and inform the targeting of EV-associated tau as potential therapeutic and biomarker strategies for AD.

Hyponatraemia in older people as a sign of adrenal insufficiency: a case-control study.

BACKGROUND: Hyponatraemia is a common cause of hospitalisation in older adults. Adrenal insufficiency (AI) can result in hyponatraemia. AIM: The aim of our study was to determine the frequency and characteristics of AI in elderly patients with hyponatraemia. METHODS: Thirty patients ≥65 years with Na(+) ≤130 mmol/L and 30 age-matched control subjects, all hospitalised, were included in the study. Plasma cortisol levels were determined before and after intravenous administration of 1 µg synthetic adrenocorticotropin hormone. A peak cortisol >550 nmol/L was considered to exclude AI. RESULTS: Sodium levels were 125 ± 5 and 139.8 ± 2 mmol/L in the hyponatremic and control groups respectively. Baseline cortisol <550 nmol/L was found in a half of hyponatremic patients. However, stimulated cortisol levels were compatible with AI in only one case (3%) and none of the controls. The mean cortisol levels were significantly higher in hyponatremic compared with control subjects, both in the basal state (585 ± 215 and 381 ± 135 nmol/L, respectively, P < 0.001) and after stimulation (933 ± 254 and 781 ± 160 nmol/L, P < 0.05). However, the incremental increase in cortisol levels after stimulation was similar in the two groups (361 ± 196 and 403 ± 155 nmol/L) CONCLUSIONS: AI is an uncommon cause of hyponatraemia in older age. Based on this small cohort, AI may be present in 3% of elderly patients with hyponatraemia. AI cannot be excluded by baseline cortisol in a significant minority of hyponatremic patients and further testing with adrenocorticotropin hormone stimulation is needed.

Incidental non-secreting adrenal masses in cancer patients: intra-individual comparison of 18F-fluorodeoxyglucose positron emission tomography/computed tomography with computed tomography and shift magnetic resonance imaging.

The ability of integrated (18)F-fluorodeoxyglucose positron emission tomography and computed tomography (FDG PET/CT) to distinguish between benign and malignant incidental non-secreting adrenal masses was evaluated in cancer patients. Results were compared with those of CT and shift magnetic resonance imaging (MRI). A total of 1832 cancer patients who had undergone FDG PET/CT scans were retrospectively evaluated. Visual interpretation, tumour maximum standardized uptake value (SUV(max)), liver SUV(max) and tumour/liver SUV(max) ratios were correlated with the findings of CT, shift MRI and final diagnosis (based on biopsy or clinical/radiological follow-up). A total of 109 adrenal masses were found: 49 were malignant and 60 were benign on final diagnosis. A tumour/liver SUV(max) ratio threshold of 1.0 was more accurate in differentiating the tumour type than tumour SUV(max) or visual interpretation alone. Diagnostic accuracy of CT and shift MRI (92 - 97%) was similar to that for FDG PET/CT (94 - 97%). In conclusion, FDG PET/CT accurately characterizes adrenal tumours, with excellent sensitivity and specificity. Use of 1.0 as the threshold for the tumour/liver SUV(max) ratio seems to be promising for distinguishing benign from malignant adrenal masses in cancer patients.

[Diagnosis of fever of unknown origin (FUO). Positron emission tomography/computed tomography (PET-CT)]. / Diagnostik bei Fieber unklarer Genese (FUO) - Positronen-Emissions-Tomographie/Computertomographie(PET-CT).

Nuclear medicine imaging is now well accepted for the localization of septic foci. But in patients the results of infection scintigraphy, radiology and ultrasound remain unsatisfactory in the diagnosis of fever of unknown origin (FUO). In contrast to septic infections, patients with FUO - mostly in elderly patients - tend to have such conditions as occult tumours, atypical pneumonia, hematoblastosis, malignant lymphomas. (18)F(Fluor-18)-Fluordeoxyglucose-PET ((18)F-FDG PET) has made it possible to localize symptomatically occult changes with a high diagnostic accuracy and to achieve differentiation between benign and malignant changes.

(99m)Tc-Fab' fragments (sulesomab) for imaging septically loosened total knee arthroplasty.

The diagnostic accuracy of infection scintigraphy with (99m)Tc-labelled monoclonal antibody Fab' fragments (sulesomab) was studied in patients with suspected total knee arthroplasty (TKA) infection. Images from 26 patients were evaluated by two independent readers and compared with a quantitative interpretation of time-activity courses. Microbiological examinations and joint aspiration results were used as reference standards. Histologically, aseptic TKA loosening occurred in two patients and severe, moderate or mild septic loosening in four, nine and 11 patients, respectively. Diagnostic accuracy for severe infection was 100% for both readers, whereas for moderate infection accuracy decreased by 12% and 12% for readers one and two, respectively. For mild infection a further decrease of approximately 61% and 52% occurred for readers one and two, respectively. Quantitative evaluation gave significantly better results over visual interpretation with a diagnostic accuracy of 100% for severe infection and decreased by only 10% and 15% in patients with moderate and mild infection, respectively. Quantitative evaluation of (99m)Tc-Fab' fragments is highly sensitive and specific for diagnostic imaging of infection in patients with septically-loosened TKA.

[Nuclear medical imaging in case of painful knee arthroplasty]. / Nuklearmedizinische Diagnostik bei schmerzhafter Knieprothese.

RATIONALE: The aim of the present study was to calculate the overall diagnostic accuracy of nuclear medical imaging in patients with painful knee arthroplasty. MATERIAL AND METHODS: This retrospective study of all patients (n=87) where a (99m)Tc-triple phase bone scintigraphy (TPBS; n=120) and (99m)Tc-anti-granulocyte scintigraphy (BW 250/183; n=20) for a painful knee arthroplasty was performed between 2003 and 2007. RESULTS: A total of 87 patients with 94 knee arthroplasties were examined to detect septic and aseptic loosening and to differentiate between them. The sensitivity, specificity, the positive and negative predictive value and accuracy of TPBS for the detection of septic knee arthroplasty loosening was 100%, 85%, 55%, 100%, 73% and for BW 250/183 was 91%, 66%, 76%, 85%, 80% for sepsis, respectively. A significant increase in diagnostic accuracy with 94%, 88%, 89%, 95% und 89% (p <0.001) could be achieved when both methods were used in combination. CONCLUSION: Both methods alone have high negative predictive values, but the combination of both is complementary and significantly increases the diagnostic accuracy and positive predictive value for final diagnosis of knee arthroplasty loosening.

Quantitative [(123)I]FP-CIT pinhole SPECT imaging predicts striatal dopamine levels, but not number of nigral neurons in different mouse models of Parkinson's disease.

Single photon emission computed tomography (SPECT) using [(123)I]FP-CIT as radioligand for the dopamine transporter has become a widely used tool to monitor the integrity of the nigrostriatal dopaminergic projection in Parkinson's disease (PD). Previous studies with pinhole SPECT in small animals have demonstrated that the striatal [(123)I]FP-CIT binding indeed correlates with the striatal dopamine transporter protein level. It is unclear, however, if there is a stable relationship between the striatal [(123)I]FP-CIT binding and other functionally important parameters of the nigrostriatal system, such as the striatal dopamine levels and the number of dopaminergic neurons in the substantia nigra. To assess this question experimentally, we studied two different mouse models of PD, namely a mild 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine intoxication paradigm, to model mild nigrostriatal damage and the intrastriatal 6-hydroxydopamine paradigm to model more advanced nigrostriatal damage. Our data demonstrate that the striatal [(123)I]FP-CIT binding measured by SPECT in vivo precisely predicts the striatal dopamine concentrations, but does not necessarily correlate with the nigral dopaminergic cell number. Thus, the present work underscores that FP-CIT SPECT does only allow judging the integrity of the striatal dopaminergic nerve terminals, but not the nigral dopaminergic cells in PD. This finding may have significant impact on the use of [(123)I]FP-CIT SPECT as a surrogate marker for clinical trials aimed at measuring neuroprotection.

Scintigraphy with 99mTc-labeled heat-altered erythrocytes in diagnosing hyposplenia: prospective comparison to 99mTc-labeled colloids and colour-coded duplex ultrasonography.

AIM: Ultrasound may be a cheap alternative to scintigraphic determination of splenic function. We directly compared nanocolloid scintigraphy (NS), scintigraphy with heat-altered erythrocytes (ES), and colour-coded Doppler sonography (DS) in patients with chronic inflammatory bowel disease (CIBD). PATIENTS, METHODS: 35 patients were included into the study. Clearance rates were determined in ES, spleen/liver ratios (SLR) were measured scintigraphically in ES/NS. In DS, spleen size, echogenicity, and vascular resistance indices (RI) were determined. The results were compared to each other, to the clinical activity scores for CIBD, and to the course of the disease. RESULTS: Based on the blood erythrocyte clearance serving as standard, patients had a good (19 patients), impaired (5), or missing splenic function (11). There was a good correlation of the clearance to SLR in ES (0.63, p < 0.01). The 10 min / 45 min ES clearance showed a high correlation (Spearman-Rho 0.87, p < 0.01). The SLR in ES at 2, 5, 10 and 45 min also correlated well with each other (Spearman-Rho > 0.9, p < 0.01; SLR > 3.45 normal splenic function, SLR < 1.22 indicated hyposplenia). There were no correlations between the results of NS, DS, Howell-Jolly-bodies, or clinical parameters. Only ES and the erythrocyte clearance correlated well. Howell-Jolly-Bodies detected 1 of 11 patients with hyposplenia while false-positive in 4. CONCLUSION: Ultrasound and colloid scintigraphy show a low correlation with clearance of heat-altered erythrocytes. Only ES shows a good correlation in patients with CIBD. The clearance at 10 min already reliably determines splenic function. SLR may be determined after 10 minutes and is predictive of normal function if above 3.45 while SLR < 1.2 indicated hyposplenia.

Role of p38 mitogen-activated protein kinase in cardiac remodelling.

BACKGROUND AND PURPOSE: Mitogen-activated protein kinases (MAPK) are centrally involved in several mechanisms important for heart failure such as apoptosis, activation of inflammatory responses and cell proliferation. We therefore evaluated the effect of the selective p38 MAPK inhibitor SB 239063 on progression of left ventricular remodelling after myocardial infarction (MI) in rats. EXPERIMENTAL APPROACH: Rats were treated for 9 weeks with placebo or SB 239063 by gavage (15 mg kg(-1)) twice daily starting 7 days after ligation of the left anterior descending artery. Serial transthoracic echocardiography was performed at days 7, 36 and 70. KEY RESULTS: Over the 9 weeks, mortality was not different between the groups. On echocardiography, animals after myocardial infarction exhibited significant left ventricular dilatation as expected (week 10, end-systolic diameter, placebo sham 5.21+/- 0.34 vs. placebo MI 8.44+/- 0.57 mm). However, there was no difference between placebo and SB 239063-treated rats (week 10, end-systolic diameter, SB MI 7.76+/- 0.74 mm, not significantly different from placebo MI). Haemodynamics changed accordingly. Moreover, SB 239063 had no effect on left ventricular hypertrophy. Treatment with SB 239063 significantly reduced cytokine expression of tumour necrosis factor and interleukin-1beta after myocardial infarction. However, collagen content was not influenced by the treatment. CONCLUSION: Despite a reduction of inflammation, treatment with the p38 inhibitor SB 239063 does not affect cardiac remodelling and cardiac function when treatment is started 7 days after myocardial infarction.

What is the best pre-therapeutic dosimetry for successful radioiodine therapy of multifocal autonomy?

PURPOSE: Dose calculation for radioiodine therapy (RIT) of multifocal autonomies (MFA) is a problem as therapeutic outcome may be worse than in other kinds of autonomies. We compared different dosimetric concepts in our patients. PATIENTS, METHODS: Data from 187 patients who had undergone RIT for MFA (Marinelli algorithm, volumetric compromise) were included in the study. For calculation, either a standard or a measured half-life had been used and the dosimetric compromise (150 Gy, total thyroid volume). Therapeutic activities were calculated by 2 alternative concepts and compared to therapeutic success achieved (concept of TcTUs-based calculation of autonomous volume with 300 Gy and TcTUs-based adaptation of target dose on total thyroid volume). RESULTS: If a standard half-life is used, therapeutic success was achieved in 90.2% (hypothyroidism 23,1%, n = 143). If a measured half-life was used the success rate was 93.1% (13,6% hypothyroidism, n = 44). These differences were statistically not significant, neither for all patients together nor for subgroups eu-, hypo-, or hyperthyroid after therapy (ANOVA, all p > 0.05). The alternative dosimetric concepts would have resulted either in significantly lower organ doses (TcTUs-based calculation of autonomous volume; 80.76 +/- 80.6 Gy versus 125.6 +/- 46.3 Gy; p < 0.0001) or in systematic over-treatment with significantly higher doses (TcTUs-adapted concept; 164.2 +/- 101.7 Gy versus 125.6 +/- 46.3 Gy; p = 0.0097). CONCLUSIONS: TcTUsbased determination of the autonomous volume should not be performed, the TcTUs-based adaptation of the target dose will only increase the rate of hypothyroidism. A standard half-life may be used in pre-therapeutic dosimetry for RIT of MFA. If so, individual therapeutic activities may be calculated based on thyroid size corrected to the 24h ITUs without using Marinelli's algorithm.

Decrease of (99m)Tc-uptake in autonomous thyroid tissue in Germany since the 1970s. Clinical implications for radioiodine therapy.

AIM: The clinical relevance of thyroidal autonomy, i.e. the risk of a patient to become hyperthyroid after exposure to iodine, can be estimated by measurement of the thyroidal (99m)Tc uptake under suppression of TSH (TcTUs). The upper tolerable limit has been set to 2% some 25 years ago. Considering the increase in nutritional iodine uptake over the last 15 years, we wanted to find out if the TcTUs per ml of autonomous volume may have changed. PATIENTS, METHODS: We performed a pilot study in 1166 randomly chosen patients from 1980-2003 with different kinds of benign thyroid disorders to determine changes in TcTU or TcTUs over time. A second analysis was performed in 1063 patients from 1987-2004 with unifocal autonomy (UFA). In these patients, the volume of the autonomous tissue can be determined precisely thus allowing for exact determination of TcTUs per ml of autonomous volume. RESULTS: The pilot study demonstrated that the TcTUs or the TcTU has been falling over the last 25 years in all benign thyroid disorders (p < 0.01). The total thyroid volume has also been decreasing in all disorders. In the second analysis of UFA only, 500 from the 1063 patients fulfilled the inclusion criteria. In these patients, the TcTUs per ml of autonomous volume has fallen from an average of 0.48% to an average of 0.28%. These results are statistically significant as determined by ANOVA testing (p = 0.032). CONCLUSION: As the TcTUs in relation to autonomous volume has dropped by approximately 40% over the last 25 years, the upper limit for a normal TcTUs should be reduced to 1-1.4%, dependent on regional factors.

Combination of 'idiopathic' REM sleep behaviour disorder and olfactory dysfunction as possible indicator for alpha-synucleinopathy demonstrated by dopamine transporter FP-CIT-SPECT.

REM sleep behaviour disorder (RBD) and olfactory dysfunction are common and very early features of alpha-synucleinopathies, in particular Parkinson's disease. To investigate the hypothesis that these two clinical features in combination are an indicator of evolving alpha-synucleinopathy, olfactory function was assessed in RBD. We studied 30 patients (18 male, 12 female; mean age 48 +/- 14 years, range 19-78 years) with clinical (idiopathic, n = 6; symptomatic, n = 13, mostly associated with narcolepsy) or subclinical (n = 11, associated with narcolepsy) RBD according to standard criteria and 30 age- and gender-matched healthy control subjects using standardized 'Sniffin' Sticks'. RBD patients had a significantly higher olfactory threshold (P = 0.0001), lower discrimination score (P = 0.003), and lower identification score (P = 0.001). Compared with normative data, 97% of the RBD patients had a pathologically increased olfactory threshold, 63% an impaired odour discrimination score, and 63% a decreased identification score. On neurological examination, signs of parkinsonism were newly found in five patients with clinical RBD (not associated with narcolepsy), who usually had a long history of 'idiopathic' RBD. Four of the five patients fulfilled the UK Brain Bank criteria for the clinical diagnosis of Parkinson's disease. The underlying nigrostriatal degeneration of clinical Parkinson's disease was confirmed by I-123-FP-CIT SPECT in one patient and early nigrostriatal degeneration was identified by SPECT in a further two patients with 'idiopathic' clinical RBD out of 11 RBD patients who agreed to undergo SPECT studies. Our study shows that RBD patients have a profound impairment of olfactory function. Five patients with clinical RBD not associated with narcolepsy had clinical or imaging signs of nigrostriatal degeneration. This new clinical finding correlates with the neuropathological staging of Parkinson's disease (stages 1-3) as proposed by Braak. In stage 1, the anterior olfactory nucleus or the olfactory bulb is affected (along with the dorsal motor nucleus of the glossopharyngeal and vagal nerves). In stage 2, additional lesions consistently remain confined to the medulla oblongata and pontine tegmentum, which are critical areas for RBD. Midbrain lesions are found only in stage 3, in particular degeneration of dopaminergic neurons in the substantia nigra pars compacta. Thus, 'idiopathic' RBD patients with olfactory impairment might present with stage 2 preclinical alpha-synucleinopathy. Since narcoleptic patients are not known to have an increased risk of developing parkinsonism, the pathophysiology and clinical relevance of hyposmia in RBD/narcolepsy patients requires further research.

[Guideline for radioimmunotherapy of rituximab relapsed or refractory CD20(+) follicular B-cell non-Hodgkin's lymphoma]. / Leitlinie für die Radioimmuntherapie des rezidivierenden oder refraktären CD20-positiven follikulären B-Zell-Non-Hodgkin-Lymphoms.

This guideline is a prerequisite for the quality management in the treatment of non-Hodgkin-lymphomas using radioimmunotherapy. It is based on an interdisciplinary consensus and contains background information and definitions as well as specified indications and detailed contraindications of treatment. Essential topics are the requirements for institutions performing the therapy. For instance, presence of an expert for medical physics, intense cooperation with all colleagues committed to treatment of lymphomas, and a certificate of instruction in radiochemical labelling and quality control are required. Furthermore, it is specified which patient data have to be available prior to performance of therapy and how the treatment has to be carried out technically. Here, quality control and documentation of labelling are of greatest importance. After treatment, clinical quality control is mandatory (work-up of therapy data and follow-up of patients). Essential elements of follow-up are specified in detail. The complete treatment inclusive after-care has to be realised in close cooperation with those colleagues (haematology-oncology) who propose, in general, radioimmunotherapy under consideration of the development of the disease.

Development and clinical application of peptide-based radiopharmaceuticals.

Peptide-based radiopharmaceuticals have been introduced into clinical work more than a decade ago. The first and most successful imaging agent to date is the somatostatin analog octreotide. It is used for somatostatin receptor scintigraphy and also receptor-mediated peptide-radiotherapy of neuroendocrine tumors. For in vivo use as radiopharmaceutical, the natural peptide is modified in order to enhance the metabolic stability and to allow stable labeling with a so-called residualizing label. This means, that a radiometal chelator complex bound to a modified peptide stable in serum is internalized into the target cells via a specific receptor. The peptide then undergoes lysosomal degradation leaving the radiometal-chelator complex trapped inside the cell, leading to a high target to background ratio. The successful development of new radiopeptides is thus dependent on modifications of a given natural peptide while preserving the binding affinity for the target receptor(s) at the same time. Other peptides than somatostatin are under development for use as radiopeptides such as Minigastrin, GLP-1, VIP, Substance P, or Neurotensin. Some show very favorable results in clinical trials, like Minigastrin for example. Furthermore, there is increasing interest in peptide-binding sites other than the "classical" receptors for regulatory peptides specifically over-expressed by (neuroendocrine) tumors. In this paper, we provide an overview of the biochemical and radiochemical aspects of radiopeptide development, the current state of clinical use of radiopeptides for diagnosis and therapy of tumors, the current state of development of new compounds, and future developments.

Endoscopic sentinel lymphadenectomy as a new diagnostic approach in the N0 neck.

Sentinel lymphadenectomy was developed to reduce the extent of surgical interventions in cancer patients. The sentinel node (SN) concept was first established for melanoma and breast cancer; within some years, it also became increasingly popular for head and neck cancer. As soon as the required sensitivity of the method proves to be feasible in the daily clinical routine, the discussion about the best surgical approach to single or multiple SN(s) will arise. Different objectives may here compete with each other. The incision should render the best exposure of the operation site and should be expandable in case further lymph node regions have to be dissected. Finally, a good functional as well as a good cosmetic result is desirable. Endoscopic lymph node excisions were performed in patients suffering from squamous cell carcinoma of the upper aerodigestive tract located in different sites (1x uvula, 2x epiglottis, 1x glottis). In preoperatively performed ultrasonic imaging (B-mode-ultrasonography), N0 necks were assessed. In contrast to previously reported endoscopic techniques in humans, the presented method requires no insufflation of carbon dioxide or external retraction of the skin. Following laser surgical resection of the primary tumor, the SN and further lymph node(s) with accumulation of tracer substance were identified and resected endoscopically via an incision that was afterwards extended to a normal neck dissection incision. Reports of histopathologic examination of the sentinel node(s) were compared to the respective neck dissection specimens. The presented method may help to reduce the degree of invasiveness frequently attributed to sentinel lymphadenectomy once the method has been established for head and neck cancer.

99mTc-labeling and in vitro and in vivo evaluation of HYNIC- and (Nalpha-His)acetic acid-modified [D-Glu1]-minigastrin.

Gastrin/CCK-2 receptors are overexpressed in a number of tumors such as medullary thyroid cancer (MTC) and small cell lung cancer (SCLC). Recently [D-Glu1]-minigastrin (MG) has been radiolabeled with 131I, 111In, and 90Y and evaluated in patients. This study describes the labeling and evaluation of MG with technetium-99m using two different labeling approaches: HYNIC as bifunctional coupling agent and (Nalpha-His)Ac as tridentate ligand for 99mTc(CO3) labeling. Labeling was perfomed at high specific activities using Tricine and EDDA as coligands for HYNIC-MG and [99mTc(OH2)3(CO)3]+ for (Nalpha-His)Ac-MG. Stability experiments were carried out by reversed phase HPLC analysis in PBS, serum, histidine, and cysteine solutions, as well as rat liver and kidney homogenates. Receptor binding and internalization experiments were performed using CCK-2 receptor positive AR42J rat pancreatic tumor cells. Biodistribution experiments were carried out in nude mice carrying AR42J tumors by injection of 99mTc-labeled peptide with or without coinjection of 50 microg of minigastrin I human (MGh). HYNIC-MG and (Nalpha-His)Ac-MG could be radiolabeled at high specific activities (>1 Ci/micromol). For HYNIC-MG, high labeling yields (>95%) were achieved using Tricine and EDDA as coligands. Stability experiments of all 99mTc-labeled conjugates revealed a high stability of the label in PBS and serum as well as toward challenge with histidine and cysteine. Incubation in kidney homogenates resulted in a rapid degradation of all conjugates with <10% intact peptide after 60 min at 37 degrees C, with no considerable differences between the radiolabeled conjugates; a somewhat lower degradation rate was seen in liver homogenates. Protein binding varied considerably with lowest levels for 99mTc-EDDA/HYNIC-MG. Competition experiments of unlabeled conjugates on AR42J membranes versus [125I-Tyr12]-gastrin I showed high CCK-2 receptor affinity for all conjugates under study. Internalization behavior was very rapid for all radiolabeled conjugates in the order of 99mTc-(Nalpha-His)Ac-MG > 99mTc-EDDA/HYNIC-MG > 99mTc-Tricine/HYNIC-MG. In tumor-bearing nude mice the highest tumor-uptake was observed with 99mTc-EDDA/HYNIC-MG (8.1%ID/g) followed by 99mTc-Tricine/HYNIC-MG (2.2%ID/g) and 99mTc-(Nalpha-His)Ac-MG (1.2%ID/g) which correlated with kidney uptake (101.0%ID/g, 53.8%ID/g, 1.8%ID/g respectively). In this series of compounds 99mTc-EDDA/HYNIC-MG with its very high tumor/organ ratios except for kidneys seems to be the most promising agent to target CCK-2 receptors. Despite promising properties concerning receptor binding, internalization, and in vitro stability, 99mTc-(Nalpha-His)Ac-MG showed low tumor uptake in vivo.

Case report: drug interference with MIBG uptake in a patient with metastatic paraganglioma.

Metaiodobenzylguanidine (MIBG) labelled with iodine-131 ((131)I) has become a well established therapeutic tool for inoperable metastastic tumours of paraganglioma. There are different pharmacological substances known to interfere with MIBG-uptake which may result in a false negative MIBG scan. We present the case of a 26-year-old male polytoxicomanic patient with metastatic paraganglioma, who underwent MIBG therapy. During earlier therapies, MIBG uptake in the metastatic lesions was very high. A post-therapeutic whole-body scan subsequent to recent (131)I-MIBG therapy failed to detect the vast majority of metastatic lesions-except for two. (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET) showed metastases with a similar distribution to the initial MIBG scan. The possible reasons for the discrepancy in the findings of the MIBG scans and the (18)F-FDG-PET scan are discussed with special emphasis on drug intake prior to MIBG administration, increased MIBG turn-over and unknown drug mixture interference with MIBG uptake.

Endosonographic imaging of benign and malignant pheochromocytomas.

Endosonography enables imaging of the adrenal glands, the mediastinum, and the epigastric retroperitoneal area. In this study, the diagnostic power of endosonography regarding the detection and localization of pheochromocytomas and the differentiation between benign and malignant lesions and their metastases and recurrences was investigated. Endosonography was performed using a Pentax FG 32 UA endosonoscope with a longitudinal 7.5-MHz sector array from the esophagus, stomach, and duodenum. A total of 22 pheochromocytomas in 11 patients were studied. All these tumors, recurrences, and metastases were histologically proven except in one single patient where pheochromocytoma had been diagnosed histologically in the past, and actual findings were obvious local recurrence and four metastases. Malignant pheochromocytoma (n = 10) tended to be larger at the time of examination than benign pheochromocytoma (n = 12; P = 0.069). No significant differences between benign and malignant pheochromocytomas regarding echogeneity and echostructure could be detected. However, hyperechoic echogeneity was seen only in benign lesions, which, however, had variable echogeneity. If confirmed by future observations, hyperechoic echogeneity may be considered to be suggestive of a benign nature. In several cases, endosonography detected small lesions that had been missed by routine diagnostic procedures and yielded helpful information for planning surgical strategy. In conclusion, endosonography is considered to be useful in early detection of pheochromocytomas, and in malignant disease of recurrence and metastases.

LeukoScan for imaging infection in different clinical settings: a retrospective evaluation and extended review of the literature.

PURPOSE: The aim of the current study was to determine the overall diagnostic accuracy of Tc-99m-labeled antigranulocyte monoclonal antibody Fab' fragments (LeukoScan) for the routine detection of bone and soft tissue infections in a retrospective evaluation. PATIENTS AND METHODS: 138 patients (63 men, 75 women; mean age, 58.29 +/- 25.38 years) with fever of unknown origin and possible endocarditis (n = 59), infection of arthroplastic joints (n = 20), arthritis (n = 16), peripheral (n = 15) and central bone infections (n = 14), soft tissue infection (n = 6), appendicitis (n = 4), pericarditis (n = 2), or vascular graft infection (n = 2) underwent imaging after injection of 555 to 925 MBq (15 to 25 mCi) Tc-99m-labeled antigranulocyte monoclonal antibody Fab' fragments (LeukoScan). RESULTS: True-positive results were found in 63 of 81 lesions. The overall sensitivity and specificity were 76% and 84%, respectively. In arthritis, seven of seven foci could be detected, whereas false-negative results were found in infections of the femoral bone in three of nine lesions and in periprosthetic infections of long bones in three of eight lesions. Good results were found in five of six soft-tissue infections, in four of six patients with endocarditis, in three of four atypical cases of appendicitis, in two of two infected vascular grafts, and in one of one patient with pericarditis. Subacute and chronic infections of the spine always showed photopenic areas in eight of eight patients. If photopenic lesions were included as diagnostic criteria, the sensitivity and specificity were 88% and 67%, respectively. CONCLUSIONS: Tc-99m-labeled antigranulocyte monoclonal antibody Fab' fragments can be used for imaging acute infections of peripheral bones and soft tissues. False-negative results are likely in patients with chronic infections. Sensitivity can be increased while decreasing specificity by including photopenic lesions in the spine as diagnostic criteria for localizing disease.