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International audience; In the present study, we evaluated, in mice, the efficacy of the tetrafunctional block copolymer 704 as a nonviral gene delivery vector to the lungs. SPECT/CT molecular imaging of gene expression, biochemical assays, and immunohistochemistry were used. Our dataset shows that the formulation 704 resulted in higher levels of reporter gene expression than the GL67A formulation currently being used in a clinical trial in cystic fibrosis patients. The inflammatory response associated with this gene transfer was lower than that induced by the GL67A formulation, and the 704 formulation was amenable to repeated administrations. The cell types transfected by the 704 formulation were type I and type II pneumocytes, and transgene expression could not be detected in macrophages. These results emphasize the relevance of the 704 formulation as a nonviral gene delivery vector for lung gene therapy. Further studies will be required to validate this vector in larger animals, in which the lungs are more similar to human lungs.

Assessment of myocardial viability is an important clinical issue for patient management during the acute and chronic stages of myocardial infarction. BMIPP (15-(p-iodophenyl)-3-(R,S)-methyl pentadecanoic acid) is a free fatty acid analogue which is trapped in the myocardium, thus permitting for metabolic imaging with single photon emission computerized tomography (SPECT). Less BMIPP than flow tracers that may be observed in the areas of infarction, may reflect the metabolic shift from fatty acid to glucose utilization in ischaemic myocardium. In this sense, the combined imaging of BMIPP and a flow tracer with SPECT may provide similar and important information as fluoro-18 deoxyglucose (FDG) and positron emission tomography (PET) regarding the assessment of myocardial viability. The purpose of this article is to review the clinical impact of BMIPP in patients with acute and with chronic left ventricular dysfunction for the identification of jeopardized but viable myocardium and the prediction of the functional outcome.

The utilisation of the Na/I symporter (NIS) and associated radiotracers as a reporter system for imaging gene expression is now reaching the clinical setting in cancer gene therapy applications. However, a formal assessment of the methodology in terms of normalisation of the data still remains to be performed, particularly in the context of the assessment of activities in individual subjects in longitudinal studies. In this context, we administered to mice a recombinant, replication-incompetent adenovirus encoding rat NIS, or a human colorectal carcinoma cell line (HT29) encoding mouse NIS. We used (99m)Tc pertechnetate as a radiotracer for SPECT/CT imaging to determine the pattern of ectopic NIS expression in longitudinal kinetic studies. Some animals of the cohort were culled and NIS expression was measured by quantitative RT-PCR and immunohistochemistry. The radioactive content of some liver biopsies was also measured ex vivo. Our results show that in longitudinal studies involving datasets taken from individual mice, the presentation of non-normalised data (activity expressed as %ID/g or %ID/cc) leads to 'noisy', and sometimes incoherent, results. This variability is due to the fact that the blood pertechnetate concentration can vary up to three-fold from day to day. Normalisation of these data with blood activities corrects for these inconsistencies. We advocate that, blood pertechnetate activity should be determined and used to normalise the activity measured in the organ/region of interest that expresses NIS ectopically. Considering that NIS imaging has already reached the clinical setting in the context of cancer gene therapy, this normalisation may be essential in order to obtain accurate and predictive information in future longitudinal clinical studies in biotherapy.

Serotonergic drugs may lead to valvular heart disease in humans and more recently also in rats. Although clinical data suggest that dose dependency and reversibility after drug cessation might occur, proof of this is lacking. For that purpose, a total of 106 rats were prospectively enrolled: 22 control animals and 7 groups of 12 rats that received daily subcutaneous serotonin injections (5, 10, 20, 30, 40, 50 and 60 mg/kg respectively) for 12 weeks. At 12 weeks, half of the animals of each group were killed for histological analysis, whereas the remaining rats were further followed (without serotonin injections) for an additional 8 weeks. After 12 weeks of serotonin treatment, aortic and mitral regurgitation (AR, MR) were more frequently observed in the high dose groups (> 30 mg/kg) compared to controls. Moreover, aortic and mitral valves were also thicker in the high dose groups compared to controls. After 8 weeks free of serotonin injections, AR and MR were no longer significantly higher than controls. Moreover, aortic and mitral valve thickness had normalized, returning to control levels. In conclusion, this study provides evidence for a dose-dependent valvular toxicity of serotonergic drugs, which appears to be reversible after drug withdrawal.

The aim of this study was the comparison of the tumour uptake and the long-term retention of [I-123]-2-I-L-phenylalanine and [I-123]-2-I-D-phenylalanine with those of [I-123]-2-I-L-tyrosine and [I-123]-2-I-D-tyrosine in RIM rhabdomyosarcoma tumour-bearing rats. The biodistribution of the radioactivity as a function of time in RIM tumour-bearing rats was measured by planar gamma camera imaging (dynamic and static). If dissection was applied, the activity in the tumours and tissues of interest was measured by gamma counting.[I-123]-2-iodo-L-phenylalanine, [I-123]-2-iodo-D-phenylalaine, [I-123] -2-I-L-tyrosine showed a considerable turnout uptake reaching a maximum between 10 and 30 min. At 30 min p.i. the differential uptake ratio values of this uptake were, respectively, 2.1, 2.3, 2.5 and 1.7. The activity in the tumour was shown to be related to a tumour cell uptake and not to an increased blood pool activity. All the tracers showed a clearance from the blood to the bladder without renal retention. At longer times both L- and D-[I-123]-2-I-tyrosine were cleared for a large part from the tumours and the body. [I-123]-2-I-L-Phe and [I-123]-2-I-D-Phe showed a considerable and equal retention in the tumours: as compared with 0.5 h, 91% at 24 h and 80% at 48 h. This was related to the longer retention of activity in the blood pool noticed for these compounds (81% at 24 h and 65% at 48 h). The tumour-to-background ratio increased with 25% at those longer times. At short times all the tracers were taken up to a considerable extent in the tumours. In the RIM-bearing Wag/Rij rat model only [I-123]-2-1-L-phenylalanine and [I-123]-2-I-D-phenylalanine showed an especially high retention at long times without any significant difference between the enantiomers.

PURPOSE: 123I-2-iodo-tyrosine (123I-2IT) has been identified as a promising new amino acid tracer in animals. Uptake is mediated by LAT1 transport, which is increased in tumour cells. In this study we present the human biodistribution and first clinical results in glioma patients. METHODS: For the biodistribution study, six male volunteers received 60-95 MBq 123I-2IT. Whole-body scans and blood and urine samples were obtained up to 24 h after injection; dosimetry was calculated using OLINDA 1.0 software. Initial clinical evaluation of 123I-2IT SPECT was performed in 35 patients with suspected or known glioma, either as primary diagnosis or for detection of recurrence. Tumour-to-background (T/B) ratios were calculated for semi-quantitative analysis. The results were correlated with clinical and MRI follow-up data or histology. RESULTS: 123I-2IT showed both renal and intestinal clearance. Bladder (0.12 mGy/MBq) and small intestine (0.03 mGy/MBq) received the highest absorbed doses. The effective dose equivalent and effective dose were estimated at 0.020 and 0.016 mSv/MBq, respectively. In patients, 123I-2IT SPECT did not differentiate between neoplastic and non-neoplastic lesions after an indeterminate MRI. In follow-up of known glioma, 13/15 patients with disease recurrence had increased T/B values (range 1.39-3.91). Out of seven recurrence-negative patients, two showed an important increase in T/B, in one case due to radionecrosis (T/B 1.59) and in the other probably due to residual but stable disease (T/B 2.07). CONCLUSION: 123I-2IT has a favourable biodistribution for a tumour imaging agent. It shows increased uptake in central nervous system glioma and is potentially useful in the follow-up of glioma patients.

Positron emission tomography (PET) using fluorodeoxyglucose (FDG) plays an important role in the management of oncologic diseases. Interpretation of the FDG-PET data requires a profound knowledge of the normal variety of FDG biodistribution and of the different pitfalls that may mimic addit

To characterize the myocardium after thrombolytic therapy for infarction single photon emission computed tomographic (SPECT) studies with 123I-(ortho-iodophenyl)-pentadecanoic acid (oPPA) and 99Tcm-methoxyisobutyl isonitrile (MIBI) were obtained at rest in nine patients within a fortnight after the acute event. A decreased oPPA activity compared to MIBI was observed in 15/45 segments (7/9 patients). The segments with discordant oPPA/MIBI activities showed less severe wall motion abnormalities than the segments with concordant decreased oPPA and MIBI activities (P = 0.004). A significant association was found between discordant oPPA/MIBI activities and the early evolution of wall motion following thrombolysis: discordant oPPA/MIBI activities were present in nine of the 11 segments (82%) with improved wall motion, while the wall motion of the seven segments with similar decreased oPPA and MIBI activities was unchanged or had deteriorated (P = 0.018). It is concluded that metabolic abnormalities often persist longer than perfusion and wall motion abnormalities soon after thrombolysis, and that 123I-oPPA in combination with 99Tcm-MIBI is useful to demonstrate myocardial areas which have been salvaged by thrombolysis.

A patient with diffuse hepatic arteriovenous microfistulae suffered from secondary high-output right ventricular failure, pulmonary hypertension, and ascites, all of which could be managed by selective embolization of the hepatic artery. The vascular lesion of the liver seems to be essential, although hemorrhagic hereditary telangiectasia ,perhaps aggravated by administration of oral contraceptives, may be considered contributory factors in this case., info:eu-repo/semantics/published

Aging is associated with morphologic and functional alterations of the rat's left ventricle. However, the time-course of valvular function and morphology in normal aging rats has not yet been studied. For this purpose, 30 male Wistar rats (318 ± 5 g , 10 weeks old) underwent serial echocardiograms for 58 weeks under sodium pentobarbital 50 mg/kg IP anesthetization followed by necropsy. Histopathology was also performed in two additional groups of 10 rats at 10 and 30 weeks of age. Regurgitations were considered as any retrograde flow on 2-D or M-mode color Doppler echocardiography. Tricuspid regurgitation was already found at 10 weeks of age and became more frequent with age. Pulmonary, mitral and aortic regurgitation was seldom observed at 10 weeks but became more frequent after 30 weeks. For the mitral and aortic valve, this was also associated with an increase in valvular thickness because of nodular or segmental myxoid leaflet changes. The severity of valvular regurgitations did not increase with age. In conclusion, aging leads to morphologic and functional valvular changes in normal rats. This is important when investigating models of valvular heart disease in small animals. (E-mail: steven_droogmans@yahoo.com )