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The radiosynthesis, as well as the in vivo and ex vivo biodistribution of the 11 C radiolabelled 3-(4,5-diphenyl-1,3-oxazol-2-yl)propanal oxime (6, [11 C]SZV 1287) are reported. SZV 1287 is a novel semicarbazide-sensitive amine oxidase (SSAO) inhibitor and a promising candidate to be a novel analgesic for the treatment of neuropathic pain. Its radiolabelling was developed via a four-step radiosynthesis which started from the reaction of a Grignard reagent with [11 C]CO2 to produce [11 C]oxaprozin (3). In the next step this carboxylic acid 3 was directly reduced to yield the corresponding aldehyde, which was then converted into the oxime. [11 C]SZV 1287 was administered to male NMRI mice. The animals were examined with dynamic PET/MR imaging for 90 minutes. Biodistribution studies were performed at 10, 30, 60 and 120 minutes post injection. The accumulation of the labelled compound was observed in the brain of the animals. The main excretion pathway was found to be through the liver and intestines. These studies provide preliminary information for pharmacokinetic characterization of the SZV 1287.

The radiosynthesis, as well as the in vivo and ex vivo biodistribution of the

"PET based" molecular imaging has significant role in personalized medicine. New radiopharmaceuticals are continuously introduced into the daily practice of detecting diseases and assessing the effectiveness of therapy. In recent years theragnostic applications have come to the forefront of radiopharmaceutical development. This article discusses, among others, radiopharmaceuticals labelled with 18F and 68Ga isotopes required for the diagnosis of neuroendocrine and prostate tumours, furthermore the inhibitors of the fibroblast activation protein. The increasing variety of metallic radioisotopes (44Sc, 64Cu, 52Mn, 86Y, 89Zr) will help meet the need for new biomarkers and will greatly facilitate the introduction of the new generation of PET radiopharmaceuticals.

Expression of multidrug pumps including P-glycoprotein (MDR1, ABCB1) in the plasma membrane of tumor cells often results in decreased intracellular accumulation of anticancer drugs causing serious impediment to successful chemotherapy. It has been shown earlier that combined treatment with UIC2 anti-Pgp monoclonal antibody (mAb) and cyclosporine A (CSA) is an effective way of blocking Pgp function. In the present work we investigated the suitability of four PET tumor diagnostic radiotracers including 2-[18F]fluoro-2-deoxy-D-glucose (18FDG),11C-methionine, 3′-deoxy-3′-[18F]fluorothymidine (18F-FLT), and [18F]fluoroazomycin-arabinofuranoside (18FAZA) forin vivofollow-up of the efficacy of chemotherapy in both Pgp positive (Pgp+) and negative (Pgp−) human tumor xenograft pairs raised in CB-17 SCID mice. Pgp+and Pgp−A2780AD/A2780 human ovarian carcinoma and KB-V1/KB-3-1 human epidermoid adenocarcinoma tumor xenografts were used to study the effect of the treatment with an anticancer drug doxorubicin combined with UIC2 and CSA. The combined treatment resulted in a significant decrease of both the tumor size and the accumulation of the tumor diagnostic tracers in the Pgp+tumors. Our results demonstrate that18FDG,18F-FLT,18FAZA, and11C-methionine are suitable PET tracers for the diagnosis andin vivofollow-up of the efficacy of tumor chemotherapy in both Pgp+and Pgp−human tumor xenografts by miniPET.

P-glycoprotein (Pgp, ABCB1) is one of the active efflux pumps that are able to extrude a large variety of chemotherapeutic drugs from the cells, causing the phenomenon of multidrug resistance. It has been shown earlier that the combined application of a class of Pgp modulators (e.g. cyclosporine A and SDZ PSC 833) used at low concentrations and UIC2 antibody is a novel, specific, and effective way of blocking Pgp function (Goda et al., 2007). In the present work we study the UIC2 antibody mediated Pgp inhibition in more detail measuring the accumulation of tumor diagnostic radiotracers, 2-[(18)F]fluoro-2-deoxy-d-glucose ((18)FDG) and [(99m)Tc]hexakis-2-methoxybutyl isonitrile ((99m)Tc-MIBI), into Pgp(+) (A2780AD) and Pgp(-) (A2780) human ovarian carcinoma cells. Co-incubation of cells with UIC2 and cyclosporine A (CSA, 2μM) increased the binding of UIC2 more than 3-fold and reverted the rhodamine 123 (R123), daunorubicin (DNR) and (99m)Tc-MIBI accumulation of the Pgp(+) 2780AD cells to approx. the same level as observed in Pgp(-) cells. Similarly, 50μM paclitaxel (Pacl) increased UIC2 binding, and consequently reinstated the uptake of R123, DNR and (99m)Tc-MIBI into the Pgp(+) cells. Blocking Pgp by combined treatments with CSA+UIC2 or Pacl+UIC2 also decreased the glucose metabolic rate of the A2780AD Pgp(+) cells measured in (18)FDG accumulation experiments suggesting that the maintenance of Pgp activity requires a considerable amount of energy. Similar treatments of the A2780 Pgp(-) cells did not result in significant change in the R123, DNR, (99m)Tc-MIBI and (18)FDG accumulation demonstrating that the above effects are Pgp-specific. Thus, combined treatment with the UIC2 antibody and Pgp modulators can completely block the function of Pgp in human ovarian carcinoma cells and this effect can be followed in vitro by using tumor-diagnostic radiotracers, (99m)Tc-MIBI and (18)FDG.

We studied how very short (10–40 min) incubation with anthracycline derivatives modifies the accumulation of PET tumor-diagnostic radiotracers in cancer cells. The human ovarian A2780 and A2780AD, human B lymphoid JY, human epidermoid KB-3-1 and KB-V-1, and smooth muscle DDT1 MF-2 cells were pre-incubated with daunorubicin and doxorubicin, and the uptake of [18F]FDG and [11C]choline was measured. Anthracycline treatment decreased remarkably the [11C]choline accumulation in a concentration dependent manner, while it did not modify significantly the [18F]FDG uptake of the cells.

BACKGROUND AND PURPOSE The antiakinetic effect of internal Globus pallidus deep brain stimulation (Gpi-DBS) in Parkinson's disease is not clear and not either how this effect is modulated by L-dopa. METHODS Left Gpi-DBS and/or L-dopa effect was studied with auditory paced right-handed sequential movements on 15O-butanol positron emission tomography (PET) in five patients. Rest and for conditions during movements (DBS off/L-dopa off; DBS on/L-dopa off; DBS off/L-dopa on; DBS on/L-dopa on) were compared with statistical parametric mapping. RESULTS Gpi-DBS activated the right supplementary motor area/premotor (SMA/PMC), and right insular cortex (IC), and as L-dopa decreased the left sensorimotor cortex (M1/S1) activity. L-dopa increased the left ventrolateral thalamus (VLTH), and decreased the left superior parietal cortex (PC) activity. Gpi-DBS and L-dopa interaction showed right SMA/PMC, IC, and left PC activation, decrease of left VLTH, PMC, and dorsolateral prefrontal cortex (PFC) activity. CONCLUSIONS The improvement of bradykinesia with Gpi-DBS is secondary and contributed to the regress of M1/S1-related rigidity and compensatory SMA/PMC, and IC activation. L-dopa and Gpi-DBS alone each reduces M1/S1 overactivity. Interaction ignores this effect, moreover has akinetic effect in the left VLTH, PMC, and PFC. Motor improvement possibly related to left PC and compensatory right SMA/PMC, and IC activation.

Our aim was to use PET/MRI to evaluate and compare the uptake of 18F-FDG, 3-deoxy-3-18F-fluorothymidine (18F-FLT), and 18F-fluorethylcholine (18F-FEC) in human pancreatic tumor cell lines after xenotransplantation into SCID mice and to correlate tumor uptake with gene expression of membrane transporters and rate-limiting enzymes for tracer uptake and tracer retention. Methods: Four weeks after orthotopic inoculation of human pancreatic carcinoma cells (PancTuI, Colo357, and BxPC3) into SCID mice, combined imaging was performed with a small-animal PET scanner and a 3-T MRI scanner using a dedicated mouse coil. Tumor-to-liver uptake ratios (TLRs) of the tracers were compared with gene expression profiles of the tumor cell lines and both normal pancreatic tissue and pancreatic tumor tissue based on gene microarray analysis and quantitative polymerase chain reaction. Results:18F-FLT showed the highest tumor uptake, with a mean TLR of 2.3, allowing correct visualization of all 12 pancreatic tumors. 18F-FDG detected only 4 of 8 tumors and had low uptake in tumors, with a mean TLR of 1.1 in visible tumors. 18F-FEC did not show any tumor uptake. Gene array analysis revealed that both hexokinase 1 as the rate-limiting enzyme for 18F-FDG trapping and pancreas-specific glucose transporter 2 were significantly downregulated whereas thymidine kinase 1, responsible for 18F-FLT trapping, was significantly upregulated in the tumor cell lines, compared with normal pancreatic duct cells and pancreatic tumor tissue. Relevant genes involved in the uptake of 18F-FEC were predominantly unaffected or downregulated in the tumor cell lines. Conclusion: In comparison to 18F-FDG and 18F-FEC, 18F-FLT was the PET tracer with the highest and most consistent uptake in various human pancreatic tumor cell lines in SCID mice. The imaging results could be explained by gene expression patterns of membrane transporters and enzymes for tracer uptake and retention as measured by gene array analysis and quantitative polymerase chain reaction in the respective cell lines. Thus, standard molecular techniques provided the basis to help explain model-specific tracer uptake patterns in xenotransplanted human tumor cell lines in mice as observed by PET.

Objective Cognitive deficit is an essential feature of schizophrenia. One of the generally used simple cognitive tasks to characterize specific cognitive dysfunctions is the auditory “oddball” paradigm. During this task, two different tones are presented with different repetition frequencies and the subject is asked to pay attention and to respond to the less frequent tone. The aim of the present study was to apply positron emission tomography (PET) to measure the regional brain blood flow changes induced by an auditory oddball task in healthy volunteers and in stable schizophrenic patients in order to detect activation differences between the two groups. Method Eight healthy volunteers and 11 schizophrenic patients were studied. The subjects carried out a specific auditory oddball task, while cerebral activation measured via the regional distribution of [ 15 O]-butanol activity changes in the PET camera was recorded. Results and discussion Task-related activation differed significantly across the patients and controls. The healthy volunteers displayed significant activation in the anterior cingulate area (Brodman Area – BA32), while in the schizophrenic patients the area was wider, including the mediofrontal regions (BA32 and BA10). The distance between the locations of maximal activation of the two populations were 33 mm and the cluster size was about twice as large in the patient group. Conclusions The present results demonstrate that the perfusion changes induced in the schizophrenic patients by this cognitive task extends over a larger part of the mediofrontal cortex than in the healthy volunteers. The different pattern of activation observed during the auditory oddball task in the schizophrenic patients suggests that a larger cortical area – and consequently a larger variety of neuronal networks – is involved in the cognitive processes in these patients. The dispersion of stimulus processing during a cognitive task requiring sustained attention and stimulus discrimination may play an important role in the pathomechanism of the disorder.

Introduction Imaging of the serotonergic innervation of the brain using positron emission tomography (PET) with the serotonin transporter (SERT) ligand [ 11 C] (+)McN5652 might be affected by serotonin in the synaptic cleft if there is relevant interaction between [ 11 C] (+)McN5652 and serotonin at the SERT. The aim of the present study therefore was to pharmacologically characterize the interaction of [ 11 C] (+)McN5652 and serotonin at the SERT. Methods In vitro saturation analyses of [ 3 H]serotonin uptake into HEK293 cells stably expressing the human SERT were performed in the absence and presence of unlabelled (+)McN5652. Data were evaluated assuming Michaelis–Menten kinetics. Results Unlabelled (+)McN5652 significantly reduced the maximal rate of serotonin transport V max of SERT without affecting the Michaelis–Menten constant K M . Conclusions This finding indicates that (+)McN5652 inhibits serotonin transport through the SERT in a noncompetitive manner. This might suggest that [ 11 C] (+)McN5652 PET is not significantly affected by endogenous serotonin.

18F-fluoro-deoxyglucose (FDG) can be considered as the "work-horse" of PET/CT and PET/MR imaging modalities. FDG provides insight in the pathophysiology of tumors and metastases from the point of view of sugar consumption. On the other hand, amino acid metabolism, expression of various receptors in the cells or on the surface of the cells, angiogenesis, appearance of hypoxic cells/tissues and apoptosis also participate in the pathophysiological processes and may have importance in determining the treatment strategy for patients or in monitoring the chosen therapy. Many molecules involved can be labeled by (18)F radionuclide but certain metabolisms require (11)C-labelled agents. Molecular imaging is of key importance in cancer research and various metal complexes containing (44)Sc, (64)Cu, (68)Ga, (86)Y, (89)Zr positron emitters can be very useful in this activity.A PET/CT és PET/MR képalkotó technika alkalmazásának „motorja” a radiofarmakonok oldaláról a 18F-fluoro-dezoxiglükóz, amely a sejtek cukorfogyasztásán keresztül mutatja be a tumorok és áttétek patofiziológiáját. Emellett azonban az aminosav-metabolizmus, a sejtfelületi és sejten belüli receptorok keletkezése, az antigének megjelenése, az angiogenezis, a hipoxiás területek kialakulása és az apoptózis mind olyan folyamatok, melyeknek ismerete szükséges lehet a tumorok és áttétek kezelési stratégiájának, valamint a kezelés sikerességének megállapításához. Számos, a felsorolt folyamatokban részt vevõ molekulába beépíthetõ a 18F-izotóp is, azonban bizonyos metabolizmusok vizsgálatához 11C-jelzett vegyületekre van szükség. Az összes felsorolt folyamat molekuláris szintû kutatásához nagyon hasznosak lehetnek azok a fémkomplexek, melyek 44Sc, 64Cu, 68Ga, 86Y, 89Zr pozitronemittáló izotópokat tartalmaznak.

2-[(18)F]fluoro-2-deoxy-d-glucose ((18)FDG) is a tumor diagnostic radiotracer of great importance in both diagnosing primary and metastatic tumors and in monitoring the efficacy of the treatment. P-glycoprotein (Pgp) is an active transporter that is often expressed in various malignancies either intrinsically or appears later upon disease progression or in response to chemotherapy. Several authors reported that the accumulation of (18)FDG in P-glycoprotein (Pgp) expressing cancer cells (Pgp(+)) and tumors is different from the accumulation of the tracer in Pgp nonexpressing (Pgp(-)) ones, therefore we investigated whether (18)FDG is a substrate or modulator of Pgp pump. Rhodamine 123 (R123) accumulation experiments and ATPase assay were used to detect whether (18)FDG is substrate for Pgp. The accumulation and efflux kinetics of (18)FDG were examined in two different human gynecologic (A2780/A2780AD and KB-3-1/KB-V1) and a mouse fibroblast (3T3 and 3T3MDR1) Pgp(+) and Pgp(-) cancer cell line pairs both in cell suspension and monolayer cultures. We found that (18)FDG and its derivatives did not affect either the R123 accumulation in Pgp(+) cells or the basal and the substrate stimulated ATPase activity of Pgp supporting that they are not substrates or modulators of the pump. Measuring the accumulation and efflux kinetics of (18)FDG in different Pgp(+) and Pgp(-) cell line pairs, we have found that the Pgp(+) cells exhibited significantly higher (p⩽0.01) (18)FDG accumulation and slightly faster (18)FDG efflux kinetics compared to their Pgp(-) counterparts. The above data support the idea that expression of Pgp may increase the energy demand of cells resulting in higher (18)FDG accumulation and faster efflux. We concluded that (18)FDG and its metabolites are not substrates of Pgp.

2-[(18)F]fluoro-2-deoxy-d-glucose ((18)FDG) is a tumor diagnostic radiotracer of great importance in both diagnosing primary and metastatic tumors and in monitoring the efficacy of the treatment. P-glycoprotein (Pgp) is an active transporter that is often expressed in various malignancies either intrinsically or appears later upon disease progression or in response to chemotherapy. Several authors reported that the accumulation of (18)FDG in P-glycoprotein (Pgp) expressing cancer cells (Pgp(+)) and tumors is different from the accumulation of the tracer in Pgp nonexpressing (Pgp(-)) ones, therefore we investigated whether (18)FDG is a substrate or modulator of Pgp pump. Rhodamine 123 (R123) accumulation experiments and ATPase assay were used to detect whether (18)FDG is substrate for Pgp. The accumulation and efflux kinetics of (18)FDG were examined in two different human gynecologic (A2780/A2780AD and KB-3-1/KB-V1) and a mouse fibroblast (3T3 and 3T3MDR1) Pgp(+) and Pgp(-) cancer cell line pairs both in cell suspension and monolayer cultures. We found that (18)FDG and its derivatives did not affect either the R123 accumulation in Pgp(+) cells or the basal and the substrate stimulated ATPase activity of Pgp supporting that they are not substrates or modulators of the pump. Measuring the accumulation and efflux kinetics of (18)FDG in different Pgp(+) and Pgp(-) cell line pairs, we have found that the Pgp(+) cells exhibited significantly higher (p⩽0.01) (18)FDG accumulation and slightly faster (18)FDG efflux kinetics compared to their Pgp(-) counterparts. The above data support the idea that expression of Pgp may increase the energy demand of cells resulting in higher (18)FDG accumulation and faster efflux. We concluded that (18)FDG and its metabolites are not substrates of Pgp.

5′-N-(2-[18F]Fluoroethyl)-carboxamidoadenosine ([18F]FNECA), a promising 18F-labelled adenosine agonist has been prepared by two different synthetic routes. In the first, [18F]fluoride was reacted with 5′-N,N-ethylene-2,′,3′-O-isopropylidenecarboxamido-adenosine and after removing the protective group [18F]FNECA was obtained in a low radiochemical yield (1±1%, means±sd, n=7, decay corrected). In the second, 2-[18F]fluoro-ethylamine was synthesised according to the literature and reacted with 2′,3′-O-isopropylideneadenosine-5′-uronic acid in the presence of a coupling agent. The following hydrolysis step provided the [18F]FNECA with a modest radiochemical yield (24±9%, n=17, based on [18F]fluoride-activity). After purification by preparative reverse phase HPLC 18·9–166·5 MBq (0·51–4·5 mCi) [18F]FNECA was obtained with a specific activity of 2·35±1·14 TBq/mmol (63·5±30·9 Ci/mmol, n-3). The total synthesis took 200 min and the decay corrected radiochemical yield based on [18F]F− activity was 17±9% (n=5) with more than 99·9% radiochemical purity. This second route provides sufficient [18F]FNECA for the subsequent biological evaluation using PET-technique. Copyright © 2000 John Wiley & Sons, Ltd.

In this study the authors use the consistency conditions of the Radon transform to aid attenuation correction in PET. The conditions are used both for estimating the parameters of a uniform elliptical attenuation distribution (without any transmission measurements) and for correcting for patient motion between the transmission and emission acquisitions. The results show that, for a uniform elliptical attenuation distribution, the reconstructed count densities obtained using attenuation correction based on the consistency conditions are within 1% of the true values. The method is shown to be fairly tolerant to the effects of photon counting statistics and to small non-uniformities in the attenuation distribution (such as skull attenuation). The results also show that the consistency conditions may be useful in correcting for patient motion. The method is shown to effectively compensate for shifts in two dimensions using both simulated and experimental data.

Objective To establish the persistence of hibernating myocardium initially detected after myocardial infarction treated with thrombolysis. Methods and results Fourteen patients underwent gated positron emission tomography with 18-fluoro-deoxyglucose and N13-ammonia at a median of 8 days after first myocardial infarction. Repeat scans were performed at a median of 13 weeks post-infarction. A total of 148 (30·9%) myocardial segments showed reduced N13-ammonia uptake at the time of the first scan compared with 154·5 (32·2%) segments at the time of repeat imaging. The median change in the number of segments with reduced perfusion was −1·0. Initially 13 subjects had hibernating myocardium, seven patients had large areas and six had smaller regions. Six (46·2%) subjects had repeat scans showing unchanged areas of hibernating tissue and seven had second scans demonstrating changes in the size of the region of hibernating myocardium. One patient had no hibernating myocardium on either scan. Conclusions Positron emission tomography performed several months after myocardial infarction demonstrates significant changes in myocardial perfusion. However, a reduction in the number of segments with reduced perfusion does not always result in an improvement in myocardial metabolism and contraction. Whilst most regions of hibernating myocardium were still present several months after infarction, in only approximately half was the size of the mismatched region unchanged. Therefore it is not possible to predict the fate of hibernating myocardium which is present after infarction.

An improved method has been developed to obtain highly enriched [123Te] tellurium for the production of medically important123I. Excitation function of the123Te(p,n)123I reaction, production yields and radionuclidic impurity levels were determined as a function of bombarding energy and target thickness.

OBJECTIVE: To establish the incidence of hibernating myocardium after myocardial infarction treated with thrombolysis and to observe differences in the clinical outcome between patients with and without hibernating tissue. METHODS: 41 patients underwent gated positron emission tomography with 18-fluorodeoxyglucose and 13N-ammonia at a median of eight days after first myocardial infarction. RESULTS: All 41 subjects had a matched perfusion-metabolism deficit in the region of myocardium indicated as the site of infarction by an electrocardiograph; 32 patients (78%) had scans which also showed at least one area of reduced blood flow and contraction with a concomitant increase in glucose uptake, representing hibernating myocardium. Patients were followed up at a median of six months: all 41 were alive and none had sustained a further infarct or cardiac arrhythmia; 17 subjects with hibernating tissue (53.1%) and two without (25%) reported chest pain after myocardial infarction. CONCLUSIONS: Hibernating myocardium is relatively common shortly after myocardial infarction treated with thrombolysis. It does not influence mortality or the incidence of postinfarction chest pain.

Study Design. Ten subjects (seven with neurogenic claudication and three control subjects) underwent examination of lower limb muscle blood flow before and after exercise using positron emission tomography. Objectives. To investigate the hypothesis that lower limb muscle ischemia was the origin of symptoms in neurogenic claudication. Background. Patients with neurogenic claudication secondary to spinal stenosis experience lower limb discomfort after exercise similar to that of ischemic claudication. However, they do not have clinical evidence of peripheral vascular disease. The authors postulated that the lower limb discomfort in patients with neurogenic claudication may arise from muscle ischemia due to inadequate dilatation of arterioles in response to exercise, this itself arising secondary to sympathetic dysfunction due to spinal stenosis. Method. Using O 15 -labeled water and positron emission tomography measured thigh and leg muscle blood flow response to exercise bilaterally in seven patients with unilateral neurogenic claudication and three constrol subjects were measured. Results. The average values obtained for mid-thigh and mid-calf muscle perfusion at rest were 2.57 ml/min/100 g tissue (2.23-3.90) and 2.39 ml/ml/100 g tissue (2.03-3.46), respectively. The average values obtained from mid-thigh and mid-calf perfusion after exercise were 4.41 ml/min/100 g tissue (2.8-6.0) and 4.87 ml/min/100 g (2.2-11.7). We found no difference in muscle perfusion between symptomatic and asymptomatic limbs in this group of patients. Conclusions. These studies suggest that muscle ischemia is not the origin is not the origin of symptoms in most patients with neurogenic claudication

Excitation functions have been measured for the natTi(p, x)48V nuclear process by the stacked-foil technique in the energy range up to 30 MeV for use as a monitor reaction for proton beams. The intercomparison shows good agreement with other monitor reactions (p + natCu, p + natNi) over the whole energy range. Excitation functions for the production of 47Sc, 44mSc, 44gSc and 43Sc isotopes and the isomeric cross section ratio of 44mSc/44gSc were also determined in the energy range from 9.0 to 17.5 MeV.

5′-Deoxy-5′-[18F]fluoro-adenosine was synthesised by nucleophilic radiofluorination reactions of 5′-deoxy-5′-haloadenosines. The homogeneous isotope exchange in 5′-deoxy-5′-fluoro-adenosine was also investigated. The conversion of these reactions was found to be rather low and depends on the strength of the halogen-carbon bond: 0.248% for chloride-, 0.488% for bromide- and 1.070% for iodide-derivative; there was no reaction observed in the case of fluoro-compound.

Purpose To evaluate the diagnostic potential of PET/CT using ([F 18 ]fluorethylcholine (FEC) for lymph node (LN) staging in high risk prostate cancer (PCa) patients prior to radical prostatectomy (RP). Patients and methods Twenty patients with localised PCa and ⩾20% LN risk according to a published nomogram were prospectively enrolled. FEC PET/CT was done minimum 14d after prostate biopsy. Afterwards, open RP and extended pelvic LN dissection (ePLND) were performed. Clinical stage, Prostate Specific Antigen (PSA) and biopsy Gleason Grading were assessed and histopathological evaluation of the RP-specimens and dissected LN has been performed. The results from PET/CT were compared with LN metastasis according to their anatomical site. Results Overall, 285 LN have been removed with a mean number of 15 nodes per patient (7–26). Of the 20 patients, 9 men were LN positive (45%), which corresponds to 31 positive LN with a mean size of 7mm (0.8–12mm). Dissection of the obturator fossa, external iliac artery/vein and internal iliac artery/vein revealed 36%, 48% and 16% of positive LN, respectively. FEC PET/CT did not detect one single positive LN, thus was false-negative in 31 metastasis and true negative in 254 LN. Conclusion Based on our results which confirmed experience from the previous studies, FEC PET/CT scan did not prove to be useful for LN staging in localised PCa prior to treatment and should thus not be applied if clinically occult metastatic disease is suspected.

For improvement of radionuclidic purity of123I a method was elaborated to obtain highly enriched [123Te] tellurium. Using this new TeO2 target the optimum irradiation conditions have been investigated for the production of123I via123Te (p,n)123I and the radionuclide impurity levels were also determined.

Excitation function for the 113Cd(p,3n)111In and 114Cd(p,4n)111In reactions were measured by the stacked-foil technique in the energy range from 63 to 3 MeV. The results were compared with theoretical calculations based on the hydrid model using the well developed computer code ALICE. For the same energy range, the effective cross-sections were determined for the natCd(p,xn)111In reactions. At the initial proton energy of 63 MeV for production of 111In from 113Cd, 114Cd and natCd the cumulative yields were found as 16.7, 15.7 and 10.4 mCi/μ Ah respectively. The contamination of the undesired nuclide 114mIn was determined. The no carrier added (NCA) 111In was separated from the cadmium cyclotron-target by a procedure based on ion exchange chemistry. The radionuclidic purity of the final radioindium was determined.

P-glycoprotein (Pgp) is an ABC (ATP binding cassette) transporter that is often overexpressed in tumours, contributing significantly to their multidrug resistance. In this study, we explored whether the radiotracers used in tumour diagnostics can be used for in vivo visualisation of Pgp-related multidrug resistance. We also examined the effects of different Pgp modulators on the accumulation of these radioligands in tumours with or without Pgp expression. In a SCID BC-17 mouse model, cells of the drug-sensitive KB-3-1 (MDR(-)) and the KB-V1 Pgp-expressing (MDR(+)) human epidermoid carcinoma cell lines were inoculated to yield tumours in opposite flanks. For in vivo scintigraphic (biodistribution) and positron emission tomography (PET) examinations, the mice were injected with technetium-99m hexakis-2-methoxybutylisonitrile ((99m)Tc-MIBI), carbon-11 labelled methionine and fluorine-18 fluoro-2-deoxy- d-glucose ((18)FDG). For validation, in vitro cell studies with (99m)Tc-MIBI,( 99m)Tc-tetrofosmin, [(11)C]methionine and (18)FDG were carried out using a gamma counter. The expression and function of the MDR product were proved by immunohistochemistry and spectrofluorimetry. (99m)Tc-MIBI uptake was significantly lower in KB-V1 cells as compared with KB-3-1-derived tumours in vivo (Pgp(+)/Pgp(-) =0.61+/-0.13; P0.01) and cells in vitro (Pgp(+)/Pgp(-) =0.08+/-0.01; P0.001).()Cyclosporin A reversed (99m)Tc-MIBI uptake in the Pgp+ cells, while verapamil failed to modify it. (18)FDG uptake was significantly higher in KB-V1 tumours (Pgp(+)/Pgp(-) =1.36+/-0.05; P0.01) and cells (Pgp(+)/Pgp(- )=1.52+/-0.12; P0.001). Whereas cyclosporin A eliminated the difference between FDG uptake in MDR(+) and MDR(-) cell lines, verapamil significantly increased it. When the animals were treated with verapamil, the ratio of (99m)Tc-MIBI uptake in the MDR(+) tumours to that in the MDR(-) tumours decreased to 0.38+/-0.05 ( P0.01), while the ratio of (18)FDG uptake increased to 2.1+/-0.3 ( P0.001). There were no significant differences in the [(11)C]methionine uptake in the MDR(+) and MDR(-) tumours and cell lines, nor was [(11)C]methionine accumulation modified by cyclosporin A. Parallel administration of (18)FDG and (99m)Tc-MIBI combined with verapamil treatment seems to be a good candidate as a non-invasive marker for the diagnosis of MDR-related Pgp expression in tumours.

In this study the authors use the consistency conditions of the Radon transform to aid attenuation correction in PET. The conditions are used both for estimating the boundary of a uniform attenuation distribution (without any transmission measurements) and for correcting for patient motion between the transmission and emission acquisitions. The results show that, for a uniform elliptical attenuation distribution, the image reconstructed with an attenuation distribution estimated using the consistency conditions is almost indistinguishable from an image reconstructed using the true attenuation coefficient map. The method is shown to be fairly tolerant to the effects of photon counting statistics and to small non-uniformities in the attenuation distribution (such as skull attenuation). The results also show that the consistency conditions may be useful in correcting for patient motion. The method is shown to accurately compensate for shifts in two dimensions using both simulated and experimental data.

The authors investigated the role of the cBZD/GABA-A receptor-complex in the regulation of rCBF by simultaneously applying [15O]-butanol-PET and TCD in therapy-resistant TLE patients. It is known that the density of the cBZD/GABA-A-receptors is reduced in the epileptogenic area of the temporal lobe, but there are no data available about the impact of this phenomenon on rCBF. FMZ is a well-known BZD-receptor antagonist which can be used to inhibit the effect mediated by cBZD/GABA-A-receptors, offering a way to study the contribution of these receptors in the determination of rCBF. The authors examined the possible correlation between the rCBF values obtained by PET and the blood flow speed readings measured by TCD in MCAs. The results show that FMZ does not cause any change in rCBF on the side of the epileptogenic focus but it significantly raises rCBF (p0.001) in the intact brain tissue on the other side. The TCD measurements showed no significant differences between the blood flow in the MCAs supplying the affected and the contralateral lobe.

Systematic research is needed to evaluate the exact role of pathological factors in the determination of the extension of the hypometabolic area in partial epileptic patients. Together with structural damage, previous seizures, deafferentation and inhibitory mechanisms may contribute to the functional disorders. Benzodiazepine receptor studies showed that the density and binding ability of these receptors decreased in the area of epileptic functional disorder. Circumscribed hypermetabolism may appear during epileptic seizures or even more electrical discharges. The authors' PET studies aimed at presurgical evaluation showed that bilateral temporal hypometabolism occurred more frequently with right-sided seizure start. FDG-PET supported the localization of the pacemaker area both in temporal lobe epilepsies and in extratemporal epilepsies. This method proved instrumental in delineating the extension of the background pathology, too. The authors also demonstrated the strength of PET brain activation in mapping the hemispheric distribution of speech functions required in the planning of surgical interventions. The role of hippocampal sclerosis in temporal lobe hypometabolism was investigated and a short account is given of the observations relating to the relationship of hypermetabolism due to subclinical epileptic discharges and cognitive deficit symptoms.

Differentiation between recurrence and post-therapeutic lesions in patients with previously treated head and neck cancer can be a real diagnostic problem. The authors discuss the role of positron emission tomography in restaging of this disease by a retrospective analysis based on 20 scans of 17 patients. PET findings were correct in identifying tumors in 85% of patients (11/13) in the group of positive PET results. All negative PET findings (4/4) were also correct during the follow-up. PET results were validated in 88% (15/17) of the patients. In one case silent distant metastases were also detected. PET is a reliable method in restaging previously treated head and neck cancer patients as it can differentiate post-therapeutic changes from tumor relapse.

The comparative analysis of two kinetic methods most frequently applied for the quantization of the results of FDG-PET brain scans was performed applying PET investigations and computer simulations. The analysis of the measured data and computer simulation demonstrated that the applicability of the results of SUV-methods to estimate glucose metabolic rates (GMR) as calculated by the Phelps-method (the most advanced method ) depended on the selected cerebral region. The distorted estimation was explained by the fact that the simpler models neglect dephosphorylation of the FDG-6P, and they also disregard the contribution of the intravascular activity to the tissue radioactivity. The simulations revealed the lack of a general and close positive correlation between SUV and GMR data; under special circumstances they might even change in an inverse manner.

The PET radiopharmaceuticals are prepared on the spot in most cases due to the short lifetime of the isotopes used. The first step of this process is the isotope production by small cyclotrons. The synthons made from the isotopes react with the precursor of the given radiopharmaceutical. The target compound selected from the reaction mixture is ready for injection after purification, formulation and sterile filtration. In addition to [18F]-FDG, [11C]-methionine and [15O]-butanol routinely used for diagnostic purposes in the PET Centre of the University of Debrecen, a number of other radiopharmaceuticals are synthesized for use in research from time to time.

The well known and widely used P1 adenosine agonist, 5'-N-ethyl-carboxamidoadenosine (NECA), was labelled with 18F isotope for the in vivo PET investigation of A1, A2 and A3 adenosine receptor expression. The precursor 2-[18F]fluoroethylamine was reacted with 2',3'-O-isopropylideneadenosine-5'-uronic acid. Specific activity of the [18F]-FNECA was (2.3 +/- 1.1) TBq/mmol (60 Ci/mmol). Dynamic PET measurements were carried out in rabbits to study the in vivo kinetics of the receptor saturation with the labelled ligand. The time dependent accumulation was followed up in the heart, lungs, liver, brain and testis. The radiotracer uptake was rapid and reached its maximum in less than two minutes in the heart and testes after v. injection of the radiopharmaceutical, while it took about 6 minutes in the brain, lungs and liver. High [18F]-FNECA accumulation was detected in the intestines, too. The specific binding of the [18F]-FNECA was tested in competition experiments in brain and heart sections using autoradiographic technique. The outlined synthesis provided sufficient amounts of [18F]-FNECA to map adenosine receptor expression under physiological conditions.

OBJECTIVE—To investigate whether QRS morphology on the surface ECG can be used to predict myocardial viability. DESIGN—ECGs of 58 patients with left ventricular impairment undergoing positron emission tomography (PET) were studied. 13N-Ammonia (NH3) and 18F-fluorodeoxyglucose (FDG) were the perfusion and the metabolic markers, respectively. The myocardium is scarred when the uptake of both markers is reduced (matched defect). Reduced NH3 uptake with persistent FDG uptake (mismatched defect) represents hibernating myocardium. First, the relation between pathological Q waves and myocardial scarring was investigated. Second, the significance of QR and QS complexes in predicting hibernating myocardium was determined. RESULTS—As a marker of matched PET defects, Q waves were specific (79%) but not sensitive (41%), with a 77% positive predictive accuracy and a poor (43%) negative predictive accuracy. The mean size of the matched PET defect associated with Q waves was 20% of the left ventricle. This was not significantly different from the size of the matched PET defects associated with no Q waves (18%). Among the regions associated with Q waves on the ECG, there were 16 regions with QR pattern (group A) and 23 regions with QS pattern (group B). The incidence of mismatched PET defects was 19% of group A and 30% of group B (NS). CONCLUSIONS—Q waves are specific but not sensitive markers of matched defects representing scarred myocardium. Q waves followed by R waves are not more likely to be associated with hibernating myocardium than QS complexes. Keywords: electrocardiography; myocardial viability; positron emission tomography; myocardial scarring

Six patients with histologically proven adenocarcinoma of the pancreas were studied using 2-deoxy-2-[18F]-fluoro-D-glucose (18F-FDG) using positron emission tomography (PET), and magnetic resonance imaging (MRI). In all six cases there was avid accumulation of 18F-FDG within the pancreatic tumour and clear visualization of the tumour on the MRI images. Delineation of the tumours was aided by superimposition of the images from the two imaging methods, which was achieved by using a system of surface markers.

Fifteen patients with locally advanced breast cancers were studied using the radiopharmaceutical 2-deoxy-2-[18F]-fluoro-D-glucose (FDG) with positron emission tomography (PET). Five patients were sequentially imaged before and after two pulses of chemotherapy. In 14 of 15 tumours increased uptake of FDG was observed which correlated with the clinical site of the tumour. The PET images were compared with the mammographic and ultrasonomammographic appearances of the tumours in selected patients. In two patients with normal mammograms PET imaging detected the tumour and in a further four patients, with suspicious but not conclusively malignant mammographic changes, a well-defined area of increased FDG uptake was demonstrated by PET. In all five sequentially imaged tumours, following chemotherapy, there was a decrease of the FDG tumour: normal breast uptake ratio. In four patients who completed a full chemotherapeutic course this change preceded a pathological response of their tumours. These findings suggest that this technique may be of benefit in imaging carcinomas in the breasts of pre-menopausal women which may appear dense on mammography and moreover, that sequential imaging may have a role in the prediction, at an early stage, of the response of locally advanced carcinomas to chemotherapy.

Proton induced nuclear reactions on enriched 111Cd and 112Cd have been studied up to 30 MeV in the context of routine production of the medically used isotope 111In with low and medium energy cyclotrons. The excitation functions of 111Cd(p,n)111m,gIn and 112Cd(p,2n)111m,gIn as production reactions and 111Cd(p,2n)110mIn, 111Cd(p,2n)110In, 111Cd(p,3n)109ml,m2,In, 112Cd(p,3n)110mIn, 112Cd(p,3n)110gIn as competing processes have been measured using the activation method involving the stacked-foil technique. The deduced thick target yields are compared with those obtained experimentally.

Excitation functions were measured for the formation of 111In in proton induced nuclear reactions on isotopically enriched 111Cd and 112Cd in the energy range up to 30 MeV. Absolute cross section values as well as differential and integral yields were deduced and compared with the earlier published data and with the experimental yield values obtained under production conditions. Routine production and chemical separation of 111In are described.

Decline of Quercus petraea forests in the northern part of Hungary (1) has been studied in the research area of the “Sikfőkut Project” (2) of the Ecological Institute of the Kossuth University, Debrecen, Hungary, from the onset of the symptoms. The aims of the investigations are to understand mechanisms and the primary reasons for the decline. Among other aspects, water uptake, transport and transpiration have been studied in both healthy and damaged trees (3), (4). The purpose of water transport measurements is to detect possible differences in the rates and velocities of water movements in the stems under different abiotic conditions. For this purpose, a radioactive tracer technique (5) has been developed. The tracer is one of the short-lived radioisotopes of alkalines in carrier-free form. The advantage of the carrier-free form is that it contains only the radioisotope itself without any contamination by other isotopes of the same chemical element. The presence of the carrier could lead to undesirable concentration effects.

In order to understand the thermal processes occurring within a water target we carried out calculations of heat transfer of the beam energy absorbed from the target water to the target back wall, and compared them with the temperatures measured during irradiations. It was shown, by both the experimental results and the heat transfer calculations, that, at high beam currents, static small volume water targets have a working temperature at the boiling point of the target water. The heat transfer occurs only by movement of the water molecules generated by the boiling target water and not by heat conduction or free convection alone. There is no heat transfer arising from vaporization and reflux.

the initial results of human clinical studies demonstrated the safety and potential benefit of autologous bone marrow cells in improving left ventricular function after acute myocardial infarction (AMI). However, a fundamental problem in developing stem cell (SC)–based therapies has been the

Simple chemical processes were used to prepare uranium oxide targets of 20 to 100 μg/cm 2 thicknesses for L shell X-ray cross section studies. U or U 3 O 8 were transformed into UCl 4 vapor and were condensated on 2 μg/cm 2 carbon backings. The UCl 4 targets were transformed back into uranium oxide. This method can also be used for other elements and compounds of high evaporation temperature.

Objective—Severe impairment of left ventricular (LV) contraction is associated with an adverse prognosis in patients with ischaemic heart disease. Revascularisation may improve the impaired LV contraction if hibernating myocardium is present. The proportion of patients likely to benefit from this intervention is unknown. Therefore, the prevalence of hibernating myocardium in patients with ischaemic heart disease and severe impairment of LV contraction was assessed. Design—From a consecutive series of patients undergoing coronary angiography for the investigation of chest pain or LV impairment, all patients with ischaemic heart disease and an LV ejection fraction (LVEF) ⩽ 30% were identified. These patients underwent positron emission tomography (PET) to detect hibernating myocardium, identified by perfusion metabolism mismatch. Setting—A teaching hospital directly serving 500 000 people. Results—Of a total of 301 patients, 36 had ischaemic heart disease and an LVEF ⩽ 30%. Twenty-seven patients had PET images, while nine patients were not imaged because of emergency revascularisation (three), loss to follow up (one), inability to give consent (four), and age