Translational imaging of the fibroblast activation protein (FAP) using the new ligand [68Ga]Ga-OncoFAP-DOTAGA.

PURPOSE: The fibroblast activation protein (FAP) is an emerging target for molecular imaging and therapy in cancer. OncoFAP is a novel small organic ligand for FAP with very high affinity. In this translational study, we establish [68Ga]Ga-OncoFAP-DOTAGA (68Ga-OncoFAP) radiolabeling, benchmark its properties in preclinical imaging, and evaluate its application in clinical PET scanning. METHODS: 68Ga-OncoFAP was synthesized in a cassette-based fully automated labeling module. Lipophilicity, affinity, and serum stability of 68Ga-OncoFAP were assessed by determining logD7.4, IC50 values, and radiochemical purity. 68Ga-OncoFAP tumor uptake and imaging properties were assessed in preclinical dynamic PET/MRI in murine subcutaneous tumor models. Finally, biodistribution and uptake in a variety of tumor types were analyzed in 12 patients based on individual clinical indications that received 163 ± 50 MBq 68Ga-OncoFAP combined with PET/CT and PET/MRI. RESULTS: 68Ga-OncoFAP radiosynthesis was accomplished with high radiochemical yields. Affinity for FAP, lipophilicity, and stability of 68Ga-OncoFAP measured are ideally suited for PET imaging. PET and gamma counting-based biodistribution demonstrated beneficial tracer kinetics and high uptake in murine FAP-expressing tumor models with high tumor-to-blood ratios of 8.6 ± 5.1 at 1 h and 38.1 ± 33.1 at 3 h p.i. Clinical 68Ga-OncoFAP-PET/CT and PET/MRI demonstrated favorable biodistribution and kinetics with high and reliable uptake in primary cancers (SUVmax 12.3 ± 2.3), lymph nodes (SUVmax 9.7 ± 8.3), and distant metastases (SUVmax up to 20.0). CONCLUSION: Favorable radiochemical properties, rapid clearance from organs and soft tissues, and intense tumor uptake validate 68Ga-OncoFAP as a powerful alternative to currently available FAP tracers.

In-vivo signatures of neurodegeneration in isolated rapid eye movement sleep behaviour disorder.

BACKGROUND AND PURPOSE: Isolated rapid eye movement sleep behaviour disorder (iRBD) is a parasomnia, recently recognized as a risk factor for progression to Parkinson's disease, dementia with Lewy body and multiple system atrophy. Biomarker studies in iRBD are relevant due to lack of evidence in this condition. The identification of biomarkers able to predict progression to synucleinopathy diseases is critical for iRBD. Fluorodeoxyglucose-positron emission tomography (FDG-PET) imaging might provide information about ongoing neurodegenerative processes. In the present study, we tested for presence of brain hypometabolism patterns as biomarkers of neurodegeneration in single iRBD individuals. METHODS: We recruited 37 subjects with polysomnography-confirmed iRBD, with neuropsychological assessment and available FDG-PET scan. Images were analysed with a validated statistical parametric mapping procedure, providing individual hypometabolism maps. RESULTS: According to the neuropsychological evaluation, 22 subjects with iRBD had normal cognition and 15 subjects showed impairments, particularly in visuoperceptive/visuospatial and memory domains. One-fifth of the cases were impaired on the Qualitative Scoring of Pentagon Test. In 32 iRBD cases, FDG-PET statistical parametric maps revealed significant cerebral hypometabolism, namely in the occipital lobes (n = 5), occipital and cerebellar regions (n = 13), occipitoparietal regions (n = 13) and a selective cerebellar hypometabolism (n = 1). Five cases had normal FDG-PET scans. CONCLUSIONS: These imaging findings indicate that brain neurodegenerative processes are present and already detectable in iRBD. The different hypometabolism patterns in the single individuals may reflect specific early pathophysiological events due to the underlying synucleinopathy, with a specific neural vulnerability for the occipital cortex that might pre-date a risk of progression towards dementia with Lewy body.

Delivery of selective internal radiation therapy complicated by variant hepatic vascular anatomy.

"Difficult vascular anatomy" is a challenge for Interventional Radiologists especially in liver directed therapies such as trans arterial radio embolization. Trans arterial radio embolization is a long and difficult procedure in which the basic knowledge of hepatic and gastro-enteric vascularization, with its high degree of variations, is very important in order to correctly administer the therapeutic drug selectively. In this report, we present a case of an atypical patient affected by an unresectable hepatocellular carcinoma, candidate for Radio-embolization treatment. His vascular anatomy was very difficult to manage, but the Interventional Radiologist was not only able to go over the "difficult anatomy," but also to take advantage of it.

REM Sleep Behavior Disorder (RBD) as a marker of neurodegenerative disorders.

Rapid eye movement (REM) sleep behavior disorder (RBD) can occur in the absence of any other obvious associated neurologic disorder or in association with a neurodegenerative disease, in which case it is considered as symptomatic RBD. RBD is frequently associated with Parkinson's disease (PD), Lewy body dementia or multiple system atrophy (MSA), and in several cases may even antedate the occurrence of motor symptoms by decades. When no neurologic disorder is obvious, RBD can be considered as idiopathic (iRBD). Several studies have looked at neurophysiologic and neuropsychological functions in iRBD and have found evidence of CNS dysfunction during both wakefulness and sleep in a variable proportion of these patients, challenging the concept of iRBD. Identifying subjects with a high risk of developing a neurodegenerative process may be crucial in order to develop early intervention strategies. Some prospective results in iRBD showed that potential markers of neurodegeneration are the following: 1) marked EEG slowing on spectral analysis; 2) decreased striatal 123I-FPCIT; 3) impaired color vision.

Effects of continuous positive airway pressure on cognitition and neuroimaging data in sleep apnea.

Obstructive sleep apnea (OSA) has been associated with a broad range of neurocognitive difficulties. The current view is that the neurocognitive impairment in OSA is due to the adverse effects of sleep fragmentation and/or intermittent hypoxia. The overall picture of cognitive deficits in OSA is complex. On balance, there appears to be negative effects of OSA on cognition, most likely in the domains of attention/vigilance, verbal and visual delayed long-term memory, visuospatial/constructional abilities, and executive dysfunction. Continuous positive airway pressure (CPAP) is the most effective and widely used treatment of OSA. In the majority of studies of OSA patients treated with CPAP, attention/vigilance improved, but changes in global functioning, executive functioning, and memory improved in about half of the studies. This may be due, in part, to variability in study design and sampling methodology across studies. Structural volume changes have been demonstrated in brain regions of OSA patients including areas that regulate memory and executive function (e.g., frontal cortex, anterior cingulate, and hippocampus). Growing evidence suggests that the OSA-related changes in brain morphology may improve with CPAP treatment. Neuroimaging studies performed during cognitive testing have provided insight into CPAP's effect on function of neuroanatomical circuits in the brain. Although neuroimaging can provide important insights into the structural and functional differences associated with OSA, one of the challenges is to interpret the findings in light of comorbid conditions that also cause neural injury. The purpose of this article is to provide a narrative review of the publications on cognition and neuroimaging in OSA before and after CPAP treatment.

End-user survey for digital sensor characteristics: a pilot questionnaire study.

OBJECTIVE: To survey end-user opinions on dental digital sensor characteristics for the design of a new X-ray imaging sensor. MATERIALS AND METHODS: 100 questionnaires were sent out to dentists and dental radiologists. The questionnaire consisted of six parts related to dental sensors. A: Details about the respondent; B: Prioritization of most important aspects of digital sensors; C: Rating advantages and D: disadvantages of digital sensors; F: Dental features that need to be enhanced by digital sensors; G: End-user comments. RESULTS: Fifty-six questionnaires were returned. Contrast resolution and imaging time were assessed as the most and the least important aspects, respectively. Aspects considered as advantages by approximately 80% of respondents were: optimal contrast resolution, increased specificity, increased discrimination between diseased and healthy tissue, increased sensitivity, lower dose to the patient by more than 20%; as a disadvantage, increased patient dose was given. Dental features considered important by over 80% of the respondents were for intraoral radiographs: the visibility of caries, periapical, periodontal, and bone lesions; for panoramic radiographs: reduction of ghost images, image sharpness and bone. Bone and soft tissues on cephalograms and bone on temporomandibular joint (TMJ) tomograms were mentioned by over 70%. CONCLUSION: The most desired characteristic for a new sensor is contrast resolution. Dose saving is not considered as important unless it is more than 20%. Examination time is not a major issue. Caries, periapical and periodontal, and bone lesions for intraoral radiographs, reduction of ghost images, image sharpness and bone for panoramic radiographs were the most frequently mentioned dental features that should be enhanced by digital sensors.

Perfluorocarbon broncho-alveolar lavage and liquid ventilation versus saline broncho-alveolar lavage in adult guinea pig experimental model of meconium inhalation.

OBJECTIVE: This study compares perfluorocarbon broncho-alveolar lavage (PFC-BAL) with isotonic saline broncho-alveolar lavage (saline-BAL) in an experimental model of meconium aspiration in adult guinea pigs. DESIGN: Prospective controlled experimental study. PATIENTS AND METHODS: Ten male guinea pigs were given 1 ml of human meconium, diluted to 10% in isotonic saline, via tracheostomy and then artificially ventilated. After stabilization, five animals (control group) underwent BAL with 10 ml/ kg isotonic saline solution. After bronchial suctioning, a further BAL with 2 ml/kg saline was performed. The other five animals (study group) underwent BAL with 100 ml/kg of PFC (RIMAR 101). Bronchosuction was effected at 5 min and then a BAL with PFC 2 ml/kg was performed. Both groups received conventional mechanical ventilation during the lavage procedures. Within 20 min all the saline-BAL treated animals died, whereas the PFC-BAL treated animals survived and were then treated with total liquid ventilation (TLV) by gravity. MEASUREMENTS AND RESULTS: After meconium inhalation in both groups, a large alveolar-arterial oxygen difference, hypercarbia, severe acidosis and tachycardia were noticed. In PFC treated animals, an improvement in blood gases was noted and acid-base balance remained stable compared to saline-BAL treated animals. No haemodynamic change was observed during or after PFC-BAL, while during saline-BAL there was evidence of bradycardia, hypotension and respiratory failure, which led to the death of the animals. The histological lung sections in the PFC-BAL group showed evidence of normal alveolar expansion with a minimal presence of meconium debris in the small bronchioles. In saline-BAL treated animals, the lung structure appeared severely compromised with the presence of meconium in bronchioles and alveoli, intra-alveolar oedema and haemorrhagic areas. CONCLUSIONS: This study confirms the detrimental effects of meconium aspiration and the impairment of lung function following saline-BAL. By contrast, PFC-BAL and TLV by gravity seemed to prevent absorption of meconium, facilitate its removal, improve gas exchange and reduce lung barotrauma.

[Artificial ventilation in children during anesthesia]. / La ventilazione artificiale in età pediatrica durante l'anestesia.

The authors describe the advantages and disadvantages, the indications and benefits on gas exchange as a result of mechanical ventilation during anaesthesia. The two models of ventilation most commonly used have been analyzed: pressure ventilators and volume preset ventilators. The former are used only in cases of short-term anaesthesia or when volume ventilators are not available. Both the most appropriate settings and ventilatory modes have been discussed regarding different paediatric ages. Particular attention has been given to the oxygen concentration in the ventilated gases (oxygen toxicity > 40%) and to barotrauma connected with high peak pressure (> 30 cm H2O). The authors suggest the type and caliber of endotracheal tube and the tidal volume for paediatric ages.

[Presentation of a case of severe abdominal infection caused by anaerobic bacteria]. / Presentazione di un caso di una grave infezione addominale da germi anaerobi.

The problem of surgical infections is discussed, special attention being paid to the commonest bacterial agents, particularly those extremely serious forms induced by gram negative and anaerobic microorganisms. After an introduction regarding isolation methods and respective therapeutic programmes, attention is turned to the case of a young woman observed after an operation for perforated appendicular abscess later complicated by stercoraceous peritonitis. After initial antibiotic treatment, which was without effect, an association comprising Clindamycin, penicillin and gentamycin was employed. In just a few days this led complete remission of symptoms.

A radioimmunoassay for human thyroglobulin: methodology and clinical applications.

A specific double-antibody radioimmunoassay with a sensitivity of 2.5 ng/ml has been developed for measuring thyroglobulin (Tg) in human serum. As endogenous anti-Tg antibodies in serum interfere in the assay, only sera with a negative tanned red cell (TRC) test are suitable for analysis. Tg was detectable in 84.7% of the euthyroid subjects, with a mean value of 6.1 (values ranging from nondetectable to 43.0 ng/ml). Values were significantly higher in women than in men. Tg release by the thyroid appears to be under pituitary control, as suggested by TSH stimulation and T3 suppression tests. Elevated Tg levels were found in hyperthyroidism, simple goitre, and differentiated thyroid carcinoma. The significance of circulating Tg and the possible application of the Tg RIA are discussed.

The effects of eledoisin on intestinal smooth muscle of ruminants.

The effects of eledoisin on the intestinal smooth muscle of ruminants are reported. The results obtained on isolated in vitro preparations from cattle suggest a direct effect of the peptide on the smooth muscle of the different intestinal sections examined. The observations made during in vivo experiments on sheep suggest that eledoisin produces its effects by also affecting the autonomic nerve supply to the intestine of these animals.

Effect of dexamethasone on thyroid hormone response to TSH.

The effect of short-term dexamethasone administration (8 mg daily for 3 days) on thyroid hormone response to exogenous TSH (bovine TSH, 5 IU i.m.) was studied in 16 euthyroid volunteers. Serum T3 and T4 concentrations were measured by radio-immunoassay prior to and 2, 6, 12, 24, and 49 hr after bTSH injection, both under basal conditions and during dexamethasone treatment. In all subjects bTSH administration raised both T3 and T4 concentrations significantly. Dexamethasone treatment induced a slight depression of endogenous TSH (m +/- SEM = 2.0 +/- 0.4 versus 1.6 +/- 0.3 muU/ml) and T4 (6.8 +/- 0.4 versus 6.1 +/- 0.2 mug/100 ml) basal values and a significant decrease in T3 value (1.16 +/- 0.09 versus 0.64 +/- 0.06 ng/ml, p = 0.005). The mean increment of both T3 and T4 after bTSH injection was percentually unchanged during dexamethasone treatment but, due to lowered basal value, T3 levels at each time interval after TSH + dexamethasone were significantly lower than the corresponding values observed after TSH alone. The present data show that high dexamethasone doses decrease T3 serum levels significantly without inhibiting T3 response to TSH stimulation. Only a slight lowering was observed in T4 levels.

[Direct radioimmunologic determination of T 3 in the serum]. / Dosaggio radioimmunologico diretto della T3 nel siero

A convenient, precise and repeatable radioimmunological method has been developed for measuring triodotironine (T3) in the serum. The dosage is made in the presence of 600 mug (micrograms) of Merthiolate in all tubes, in order to inhibit a link between the T3 and the vector proteins, and of HSA in the standards to keep them in the same condition as the samples. The method normally distinguishes 10 pg of T3 which correspond to a concentration of 0.4 ng/ml, from the point in which 25 mul of the serum are utilized. The following results have been obtained by this method: hypothyroids (14): 0.37 +/- 0.31 ng/ml; normal thyroids (51): 1.44 +/- 0.52 ng/ml; hyperthyroids (22); 4.62 +/- 1.21 ng/ml.