Lajos Trón

Publications of Lajos Trón

• [Prognostic value of FDG-PET in Hodgkin lymphoma for posttreatment evaluation. Long-term follow-up results.]

  Authors: Zsuzsa Molnár, Zsófia Simon, Zita Borbényi, Beáta Deák, László Galuska, Kármen Keresztes, Zsófia Miltényi, Imelda Marton, András Rosta, Tamás Schneider, Lajos Trón, Erika Várady, Arpád Illés

  Orvosi hetilap. 11/2009; 150(47):2133-8.

  In the past few decades Hodgkin lymphoma (HL) has become a highly curable malignant disease, as a result of using modern polychemotherapy and irradiation. Differentiation of active tumor fromIn the past few decades Hodgkin lymphoma (HL) has become a highly curable malignant disease, as a result of using modern polychemotherapy and irradiation. Differentiation of active tumor from fibrosis or necrosis within residual radiographic masses represents a problem of interpretation. Aims: The aim of this retrospective study is to assess the value of FDG-PET for prediction of remission or relapse in HL. Patients and methods: Data of 128 patients, who had residual masses on CT after completion of their planned treatment, have been analyzed. FDG-PET was performed between January 1995 and February 2005. Results: The median duration of the follow-up from PET was 75.5 months (range: 20-180 months). 89 (70%) patients had negative and 39 (30%) patients had positive FDG-PET results. The numbers of true-positive, true-negative, false-positive and false-negative subjects were 29, 83, 10 and 6, respectively. Sensitivity of post-treatment FDG-PET was 83%, specificity 93%, positive predictive value 74%, negative predictive value 93%, and accuracy 88%. The difference between the event free survival of PET positive and negative cases is highly significant (p = 0.0000), according to the Mantel-Cox test. Conclusion: Our results, in accordance with literature, clearly indicate that patients with negative FDG-PET results are unlikely to progress or relapse during a long follow-up. However, false positive uptake is a problem. We have investigated the effect of age, histological subtype, clinical stage and the type of treatment on the accuracy, but on the basis of these facts we could not find any significant difference. However, the date of the investigation influenced the results: before 2000 the number of false results was significantly higher than after that time, which shows the importance of investigators' experience.

• Pallidal Deep Brain Stimulation and L-Dopa Effect on PET Motor Activation in Advanced Parkinson's Disease.

  Authors: István Valálik, Miklós Emri, Zsolt Lengyel, Pál Mikecz, Lajos Trón, András Csókay, Teréz Márián

  Journal of neuroimaging : official journal of the American Society of Neuroimaging. 11/2008;

  ABSTRACT 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 byABSTRACT 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 (15)O-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. J Neuroimaging 2008;XX:1-6.

• Serial noninvasive in vivo positron emission tomographic tracking of percutaneously intramyocardially injected autologous porcine mesenchymal stem cells modified for transgene reporter gene expression.

  Authors: Mariann Gyöngyösi, Jeronimo Blanco, Teréz Marian, Lajos Trón, Ors Petneházy, Zsolt Petrasi, Rayyan Hemetsberger, Julio Rodriguez, Gusztáv Font, Imre J Pavo, István Kertész, László Balkay, Noemi Pavo, Aniko Posa, Miklos Emri, László Galuska, Dara L Kraitchman, Johann Wojta, Kurt Huber, Dietmar Glogar

  Circulation. Cardiovascular imaging. 09/2008; 1(2):94-103.

  BACKGROUND: Porcine bone marrow-derived mesenchymal stem cells (MSCs) were stably transfected with a lentiviral vector for transgene expression of the trifusion protein renilla luciferase, redBACKGROUND: Porcine bone marrow-derived mesenchymal stem cells (MSCs) were stably transfected with a lentiviral vector for transgene expression of the trifusion protein renilla luciferase, red fluorescent protein and herpes simplex truncated thymidine kinase (LV-RL-RFP-tTK; positron emission tomography [PET] reporter gene) for in vivo noninvasive tracking of the intramyocardially delivered MSC fate. METHODS AND RESULTS: A closed-chest, reperfused myocardial infarction was created in farm pigs. Sixteen days after myocardial infarction, LV-RL-RFP-tTK-MSCs were injected intramyocardially using electromechanical mapping guidance in the infarct border zone (n=7). PET-computed tomographic metabolic and perfusion imaging was performed after an intravenous injection of 10 mCi [18F]-FHBG and 13N-ammonia PET at 30+/-2 hours and 7 days after LV-RL-RFP-tTK-MSC treatment. Fusion imaging of the [18F]-FHBG PET-computed tomography with MRI was used to determine the myocardial location of the injected LV-RL-RFP-tTK-MSCs. Seven days after injections, [18F]-FHBG PET showed a decreased cardiac uptake with a mild increased pericardial and pleura uptake in the treated animals, which was confirmed by the measurement of luciferase activity. At 10 days, infarct size by MRI in the LV-RL-RFP-tTK-MSC-treated animals was smaller than controls (n=7) (23.3+/-1.5% versus 30.2+/-3.5%, P<0.005). The presence of the LV-RL-RFP-tTK-MSCs (5.8+/-1.1% of the injected cells) in the myocardium 10 days after intramyocardial delivery was confirmed histologically. CONCLUSIONS: Reporter gene imaging enables the tracking of the persistence of viable LV-RL-RFP-tTK-MSC in the peri-infarcted porcine myocardium at 10 days after delivery using clinical PET scanners.

• Na+/Ca2+ exchanger inhibitors modify the accumulation of tumor-diagnostic PET tracers in cancer cells.

  Authors: Teréz Márián, Judit Szabó-Péli, Eniko Németh, Lajos Trón, Elza Friedlander, Anna Szabó, László Balkay, Gábor Veress, Zoltán Krasznai

  European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences. 02/2007; 30(1):56-63.

  AIM: To establish the effects of Na(+)/Ca(2+) exchanger (NCX) blockers on 2-[(18)F]fluoro-2-deoxy-D-glucose ((18)FDG) and (11)C-choline accumulation in different cancer cells. METHODS: The tumorAIM: To establish the effects of Na(+)/Ca(2+) exchanger (NCX) blockers on 2-[(18)F]fluoro-2-deoxy-D-glucose ((18)FDG) and (11)C-choline accumulation in different cancer cells. METHODS: The tumor cells were incubated with NCX inhibitors, and the uptakes of (18)FDG and (11)C-choline were measured. Flow cytometric measurements of intracellular Ca(2+) and Na(+) concentrations were carried out. The presence of the NCX antigen in the cancer cells was proved by Western blotting, flow cytometry and confocal laser scanning microscopy. RESULTS: The NCX is expressed at a noteworthy level in the cytosol and on the cytoplasmic membrane of the examined cells. Incubation of the cells with three chemically unrelated NCX blockers (bepridil, KB-R7943 or 3',4'-dichlorobenzamil hydrochloride) resulted in an increase in the intracellular Ca(2+) concentration, with a simultaneous decrease in the intracellular Na(+) concentration. The treatment with the NCX inhibitors increased the energy consumption of the tumor cells by 50-100%. Thapsigargin abolished the NCX-induced (18)FDG accumulation in the cells. The NCX blockers applied decreased the (11)C-choline accumulation of all the investigated cancer cells by 60-80% relative to the control. CONCLUSION: A possible masking effect of NCX medication must be taken into consideration during the diagnostic interpretation of PET scans.

• Paclitaxel modifies the accumulation of tumor-diagnostic tracers in different ways in P-glycoprotein-positive and negative cancer cells.

  Authors: Zoárd Tibor Krasznai, Judit Péli-Szabó, Eniko Németh, László Balkay, Gábor Szabó, Katalin Goda, László Galuska, Lajos Trón, Tamás Major, Zoltán Hernádi

  European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences. 07/2006; 28(3):249-56.

  AIM: To study how paclitaxel treatment modifies the accumulation of tumor-diagnostic radiotracers in P-glycoprotein (P-gp) positive and negative cancer cells. METHODS: The accumulations of differentAIM: To study how paclitaxel treatment modifies the accumulation of tumor-diagnostic radiotracers in P-glycoprotein (P-gp) positive and negative cancer cells. METHODS: The accumulations of different P-gp substrates, including rhodamine 123, daunorubicin and [(99m)Tc]hexakis-2-methoxybutyl isonitrile ((99m)Tc-MIBI), were measured in P-gp-positive (A2780AD) and P-gp-negative human ovarian carcinoma cells (A2780) and JY human lymphoid B cells. The uptakes of the tumor-diagnostic tracers (11)C-choline and 2-[(18)F]fluoro-2-deoxy-d-glucose ((18)FDG) were measured in the same cell lines. The P-gp expression and function were demonstrated by flow-cytometry. RESULTS: The (18)FDG measurements revealed that the glucose metabolic rate was significantly higher (p<0.01) in the P-gp-positive A2780AD cells than in the P-gp-negative cells. Paclitaxel (1-70microM) increased the (18)FDG uptake (up to 200%) of both P-gp-positive and P-gp-negative cells, whereas it did not modulate their (11)C-choline uptake. Paclitaxel reinstated the (99m)Tc-MIBI accumulation of the A2780AD cells (to 1500% of the control) in a concentration-dependent manner, while it increased the uptake of the P-gp-negative cells to a lesser extent (to a maximum of 200% of the control). CONCLUSION: Paclitaxel modifies the uptake of tumor-diagnostic tracers in both P-gp-dependent and independent manners. Interpretation of the multifactorial effects of paclitaxel may promote a correct in vivo diagnosis of P-gp-positive and P-gp-negative tumors.

• Induced acute erythema and late pigmentation may not be correlated: in regards to Perera et al. (Int J Radiat Oncol Biol Phys 2005;62:1283-1290).

  Authors: Csaba Nemeskéri, Zsuzsa Póti, Arpád Mayer, Lajos Trón, Akos Gulybán, Géza Sáfrány, Olga Esik

  International journal of radiation oncology, biology, physics. 06/2006; 65(1):309-10.

• Brain blood flow changes measured by positron emission tomography during an auditory cognitive task in healthy volunteers and in schizophrenic patients.

  Authors: Miklós Emri, Teodóra Glaub, Roland Berecz, Zsolt Lengyel, Pál Mikecz, Imre Repa, Eniko Bartók, István Degrell, Lajos Trón

  Progress in neuro-psychopharmacology & biological psychiatry. 06/2006; 30(3):516-20.

  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"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 [15O]-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.

• Pattern of increased cerebral FDG uptake in Down syndrome patients.

  Authors: Zsolt Lengyel, Erzsébet Balogh, Miklós Emri, Edit Szikszai, József Kollár, Judit Sikula, Olga Esik, Lajos Trón, Eva Oláh

  Pediatric neurology. 05/2006; 34(4):270-5.

  Resting cerebral glucose metabolism was assessed by 18[F]-fluorodeoxyglucose in 11 Down syndrome patients. Standardized uptake values were determined on a pixel-by-pixel basis from the measuredResting cerebral glucose metabolism was assessed by 18[F]-fluorodeoxyglucose in 11 Down syndrome patients. Standardized uptake values were determined on a pixel-by-pixel basis from the measured tissue-activity data. The results revealed a mean overall 18[F]-fluorodeoxyglucose uptake in the Down syndrome patients close to that observed in the control group, consisting of children and young adults. However, the standard deviation of the standardized uptake values was much higher in the Down syndrome group in almost all voxels relating to the gray matter. The statistical parametric mapping method was applied to compare the cerebral 18[F]-fluorodeoxyglucose accumulation patterns of the Down syndrome and control groups. Six regions (clusters) were found for which the glucose uptake was higher in the Down syndrome patients than in the control group. The anatomic localization of these clusters was based on magnetic resonance investigations and a brain-atlas technique. The localization of the identified clusters with an increased glucose metabolism in the Down syndrome patients suggests that these subjects have an enhanced resting neuronal activity in cortical areas involved in reasoning, cognition, and speech as compared with normal subjects.

• Role of the Na+/Ca2+ exchanger in calcium homeostasis and human sperm motility regulation.

  Authors: Zoltán Krasznai, Zoárd Tibor Krasznai, Masaaki Morisawa, Zsuzsa Kassai Bazsáné, Zoltán Hernádi, Zsolt Fazekas, Lajos Trón, Katalin Goda, Teréz Márián

  Cell motility and the cytoskeleton. 03/2006; 63(2):66-76.

  A number of cell functions, such as flagellar beating, swimming velocity, acrosome reaction, etc., are triggered by a Ca2+ influx across the cell membrane. For appropriate physiological functions,A number of cell functions, such as flagellar beating, swimming velocity, acrosome reaction, etc., are triggered by a Ca2+ influx across the cell membrane. For appropriate physiological functions, the motile human sperm maintains the intracellular free calcium concentration ([Ca2+]i) at a submicromolar level. The objective of this study was to determine the role of the Na+/Ca2+ exchanger (NCX) in the maintenance of [Ca2+]i in human spermatozoa. Spermatozoa maintained in extracellular medium containing>or=1 microM Ca2+ exhibited motility similar to that of the control. In addition to several calcium transport mechanisms described earlier, we provide evidence that the NCX plays a crucial role in the maintenance of [Ca2+]i. Three chemically unrelated inhibitors of the NCX (bepridil, DCB (3',4'-dichlorobenzamil hydrochloride), and KB-R7943) all blocked human sperm motility in a dose and incubation time dependent manner. The IC50 values for bepridil, DCB, and KB-R7943 were 16.2, 9.8, and 5.3 microM, respectively. The treatment with the above-mentioned blockers resulted in an elevated [Ca2+]i and a decreased [Na+]i. The store-operated calcium channel (SOCC) inhibitor SKF 96365 also blocked the sperm motility (IC50=2.44 microM). The presence of the NCX antigen in the human spermatozoa was proven by flow cytometry, confocal laser scanning microscopy, and immunoblotting techniques. Calcium homeostasis of human spermatozoa is maintained by several transport proteins among which the SOCC and the NCX may play a major role.

• Biphasic accumulation kinetics of [99mTc]-hexakis-2-methoxyisobutyl isonitrile in tumour cells and its modulation by lipophilic P-glycoprotein ligands.

  Authors: Teréz Márián, László Balkay, Gábor Szabó, Zoárd T Krasznai, Zoltán Hernádi, László Galuska, Judit Szabó-Péli, Olga Esik, Lajos Trón, Zoltán Krasznai

  European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences. 07/2005; 25(2-3):201-9.

  AIM: To study the accumulation and washout kinetics of [99mTc]-hexakis-2-methoxyisobutyl isonitrile (99mTc-MIBI) in MDR positive and MDR negative tumour cells and how this is modified by lipophilicAIM: To study the accumulation and washout kinetics of [99mTc]-hexakis-2-methoxyisobutyl isonitrile (99mTc-MIBI) in MDR positive and MDR negative tumour cells and how this is modified by lipophilic P-glycoprotein ligands. METHODS: The tumour cells were incubated in the presence and absence of the ligands and the uptakes of 99mTc-MIBI, rhodamine 123 and 2-[18F]fluoro-2-deoxy-D-glucose (18FDG) were measured. RESULTS: The accumulation of 99mTc-MIBI in the tumour cells followed biphasic kinetics. Verapamil and cyclosporin A increased the membrane fluidity and significantly enhanced the 99mTc-MIBI uptake of the MDR negative cells, while the rhodamine 123 uptake was not affected. Verapamil significantly increased the uptake of rhodamine 123 and 18FDG but did not modify that of 99mTc-MIBI in the MDR positive cells. Cyclosporin A significantly increased the 18FDG uptake of the MDR positive and negative tumour cells; these effects were ouabain-sensitive. Depolarization of the cytoplasmic membrane, acidification of the extracellular medium and the administration of CCCP decreased the accumulation of 99mTc-MIBI and rhodamine 123 uptake in the tumour cells. CONCLUSIONS: Lipophilic P-glycoprotein ligands modified the biphasic accumulation kinetics of the 99mTc-MIBI uptakes of MDR negative and positive tumour cells in different and complex ways and could therefore mask the P-glycoprotein pump-dependent changes in tracer accumulation.

• [The role of positron emission tomography (PET) in the detection of local recurrence and metastases of colorectal cancer]

  Authors: Zsolt Kanyári, László Orosz, Balázs Juhász, Miklós Tanyi, Eniko Németh, Lajos Trón, Lászlo Damjanovich, Géza Lukács, Beáta Kálvin

  Magyar sebészet. 07/2005; 58(3):179-83.

  We presented here the results of PET imaging of 12 patients, previously operated on for colorectal cancer and followed at the 1st Department of Surgery, University of Debrecen. The tests were carriedWe presented here the results of PET imaging of 12 patients, previously operated on for colorectal cancer and followed at the 1st Department of Surgery, University of Debrecen. The tests were carried out using 0.15 mCi/kg FDG injections. Whole body imaging was performed in eleven patients. The indication for PET was elevated tumor marker levels in three patients, although CT scan was negative. The PET scan showed lymph node, hepatic and disseminated lymph node metastases with liver involvement in these patients. Suspicious lesions were found on CT scan in the pelvis of four patients. Local recurrence was identified in three of them, PET was negative in the fourth case. Bone scan suggested rib metastasis in one patient, which was not supported at PET investigation. In one patient, the malignant nature of large retroperitoneal lymph nodes could not be determined by CT. PET imaging proved that they were malignant and detected a previously unknown pulmonary metastasis at the same time. In one patient both pulmonary and liver metastases were seen on CT, whereas PET confirmed only the latter. Similarly, CT failed to identify liver metastasis detected at ultrasound, while PET proved it. Finally, a pulmonary metastasis detected on X-ray, could be confirmed by PET only. Based on our experience, we recommend PET-scanning with FDG when conventional imaging is equivocal and/or elevated tumor marker levels are present during follow-up. FDG-PET is important in the detection of local recurrence and metastases as well. It is advisable to use PET more often in the evaluation of patients with recurrent colorectal cancer in order to diagnose recurrences in earlier stages, which helps to identify patients who will benefit from surgery.

• Effects of miltefosine on membrane permeability and accumulation of [99mTc]-hexakis-2-methoxyisobutyl isonitrile, 2-[18F]fluoro-2-deoxy-D-glucose, daunorubucin and rhodamine123 in multidrug-resistant and sensitive cells.

  Authors: Teréz Márián, László Balkay, Lajos Trón, Zoárd T Krasznai, Judit Szabó-Péli, Zoltán Krasznai

  European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences. 05/2005; 24(5):495-501.

  Miltefosine is a phospholipid analog that exhibits antineoplastic activity against breast cancer metastases, but its mechanism of action remains uncertain. The aim of this study was to investigateMiltefosine is a phospholipid analog that exhibits antineoplastic activity against breast cancer metastases, but its mechanism of action remains uncertain. The aim of this study was to investigate the transport mechanism for the removal of miltefosine and [99mTc]-hexakis-2-methoxyisobutyl isonitrile (99mTc-MIBI) from multidrug-resistant cells. The P-glycoprotein pump function, cell viability, and 99mTc-MIBI and 2-[18F]fluoro-2-deoxy-D-glucose (18FDG) uptakes were measured in NIH 3T3 (3T3) and NIH 3T3MDR1 G185 (3T3MDR1) mouse fibroblasts and human lymphoid B JY cells. Miltefosine treatment increased the permeability and fluidity of these tumor cells in a concentration-dependent manner. The multidrug-sensitive cells were 3-4 times more sensitive to miltefosine than the multidrug-resistant ones. The extent of 99mTc-MIBI accumulation in the P-glycoprotein-expressing cells increased in the presence of miltefosine, whereas the rhodamine123 and daunorubicin uptakes of the cells did not change significantly. In the 3T3MDR1 cells verapamil reinstated the rhodamine123 and daunorubicin accumulation, but not the 99mTc-MIBI uptake. Cyclosporin A reinstated the uptakes of 99mTc-MIBI, daunorubicin and rhodamine123 by the 3T3MDR1 cells. In a concentration-dependent manner miltefosine decreased the extents of 99mTc-MIBI, rhodamine123, daunorubicin and 18FDG accumulation in the JY and 3T3 cells. Our findings indicate a common transport mechanism for 99mTc-MIBI and miltefosine, which is distinct from that for rhodamine123 and daunorubicin in MDR cells.

• [Volumetric changes following 125I interstitial brachytherapy of gliomas]

  Authors: Jeno Julow, Arpád Viola, Tibor Major, László Mangel, Gábor Bajzik, Imre Repa, Sarolta Sági, István Valálik, Miklós Emri, Lajos Trón, György Németh

  Ideggyógyászati szemle. 04/2005; 58(3-4):120-32.

  BACKGROUND: Image fusion permits quantitative analysis of the consequences of 125 Iodine interstitial irradiation of brain tumors. The volume of tumor necrosis, reactive zone and edema can beBACKGROUND: Image fusion permits quantitative analysis of the consequences of 125 Iodine interstitial irradiation of brain tumors. The volume of tumor necrosis, reactive zone and edema can be compared to the dosimetric data. PATIENTS AND METHOD: Nineteen patients with low grade glioma were analyzed on the average 14.5 months following 125 Iodine interstitial irradiation. Dose planning and image fusion were performed with the Target 1.19 (BrainLab) software. The CT/MR images showing the so called "triple ring" (necrosis, reactive ring and edema) developing after the interstitial irradiation of brain tumors were fused with the planning images and the isodose curves. The volume of the three regions was measured. Values at the intersections of isodose curves and necrosis borders were averaged and used for calculation of tumor necrosis. The volume of normal brain tissue irradiated by given dose values, as well as homogeneity and conformality indices were also determined. RESULTS: The relative volumes of the different parts of the "triple-ring" compared to the reference dose volume were the following: necrosis 54.9%, reactive zone 59.7%, and edema 445.3%. Tumor necrosis developed at 71.9 Gy dose. At the irradiation of an average size glioma with a volume of 12.7 cm3, 5 to 7 cm3 normal brain tissue around the tumor received 60-70 Gy dose. The average homogeneity and conformality indices were 0.24 and 0.57, respectively. CONCLUSION: The analysis of changes in the volume of edema, reactive ring and necrosis caused by interstitial irradiation, and their correlation with the dosimetric data using the image fusion method provide useful information for patient follow-up, clinical management and further therapeutic decisions.

• Effects of vinpocetine on the redistribution of cerebral blood flow and glucose metabolism in chronic ischemic stroke patients: a PET study.

  Authors: Géza Szilágyi, Zoltán Nagy, László Balkay, István Boros, Miklós Emri, Szabolcs Lehel, Teréz Márián, Tamás Molnár, Szabolcs Szakáll, Lajos Trón, Dániel Bereczki, László Csiba, István Fekete, Levente Kerényi, László Galuska, József Varga, Péter Bönöczk, Adám Vas, Balázs Gulyás

  Journal of the neurological sciences. 04/2005; 229-230:275-84.

  The pharmacological effects of the neuroprotective drug vinpocetine, administered intravenously in a 14-day long treatment regime, on the cerebral blood flow and cerebral glucose metabolism inThe pharmacological effects of the neuroprotective drug vinpocetine, administered intravenously in a 14-day long treatment regime, on the cerebral blood flow and cerebral glucose metabolism in chronic ischemic stroke patients (n=13) were studied with positron emission tomography in a double-blind design. The regional and global cerebral metabolic rates of glucose (CMRglc) and cerebral blood flow (CBF) as well as vital physiological parameters, clinical performance scales, and transcranial Doppler parameters were measured before and after the treatment period in patient groups treated with daily intravenous infusion with or without vinpocetine. While the global CMRglc values did not change markedly as a result of the infusion treatment with (n=6) or without (n=7) vinpocetine, the global CBF increased and regional CMRglc and CBF values showed marked changes in several brain structures in both cases, with more accentuated changes when the infusion contained vinpocetine. In the latter case the highest rCBF changes were observed in those structures in which the highest regional uptake of labelled vinpocetine was measured in other PET studies (thalamus and caudate nucleus: increases amounting to 36% and 37%, respectively). The findings indicate that a 2-week long intravenous vinpocetine treatment can contribute effectively to the redistribution of rCBF in chronic ischemic stroke patients. The effects are most pronounced in those brain regions with the highest uptake of the drug.

• Detection of prostate cancer with 11C-methionine positron emission tomography.

  Authors: György Tóth, Zsolt Lengyel, László Balkay, Morshed A Salah, Lajos Trón, Csaba Tóth

  The Journal of urology. 02/2005; 173(1):66-9; discussion 69.

  PURPOSE: We studied the detection of primary prostate cancer with positron emission tomography (PET) using C-labeled methionine (MET) in patients with increased prostate specific antigen (PSA) levelsPURPOSE: We studied the detection of primary prostate cancer with positron emission tomography (PET) using C-labeled methionine (MET) in patients with increased prostate specific antigen (PSA) levels and repeatedly negative biopsies. MATERIALS AND METHODS: A total of 20 consecutive patients with increased serum PSA and negative repeat biopsies were included in the study. Patient age ranged from 52 to 75 years (average 65). PSA levels ranged from 3.49 to 28.6 ng/ml (average 9.36). Dynamic PET images were obtained from the prostate region using C-labeled MET. Suspicious accumulations of the tracer were anatomically localized using magnetic resonance images and were used as guidance during the next biopsy. RESULTS: PET was positive in 15 (75%) patients, in 7 of whom (46.7%) the next repeat biopsy verified carcinoma. The overall detection rate was 35% (7 of 20) and 46.7% (7 of 15) in the whole group and in the positive PET group, respectively. All 5 of 5 patients with negative MET PET had negative biopsies. CONCLUSIONS: MET PET of the prostate with short dynamic scanning and multicore biopsy is a useful method to ensure a high detection rate of prostate cancer in patients with increased PSA and repeat negative biopsies.

• Partial breast irradiation with interstitial 60CO brachytherapy results in frequent grade 3 or 4 toxicity. Evidence based on a 12-year follow-up of 70 patients.

  Authors: Zsuzsa Póti, Csaba Nemeskéri, Attila Fekésházy, Géza Sáfrány, Gábor Bajzik, Zoltán P Nagy, Mária Bidlek, István Sinkovics, Nóra Udvarhelyi, Gabriella Liszkay, Imre Repa, László Galuska, Lajos Trón, Arpád Mayer, Olga Esik

  International journal of radiation oncology, biology, physics. 04/2004; 58(4):1022-33.

  PURPOSE: To investigate the radiation-induced toxicity and cosmesis of brachytherapy (BT) alone in early stage breast cancer. METHODS AND MATERIALS: A total of 70 women diagnosed with Stage I or IIPURPOSE: To investigate the radiation-induced toxicity and cosmesis of brachytherapy (BT) alone in early stage breast cancer. METHODS AND MATERIALS: A total of 70 women diagnosed with Stage I or II breast carcinoma participated in a BT study at the Municipal Oncoradiological Center, Uzsoki Hospital, Budapest, Hungary, between November 1987 and June 1992. They had undergone breast-conserving surgery with an unknown surgical margin. The postoperative tumor bed irradiation was performed with interstitial (60)Co sources with an active length of 4 cm, with 10-mm center-to-center spacing arranged in a single plane. The median number of inserted sources was 5 (range, 2-8), with a linear activity of 133-137 MBq/cm at the beginning of the study. The 50 Gy delivered dose at 5 mm from the surface of the (60)Co sources was administered during 10-22 h to the virtual postoperative lumpectomy cavity (i.e., plane). For radiobiologic considerations, the clinical target volume (CTV) was calculated retrospectively with a 10-mm safety margin, resulting in a 72-cm(3) median CTV (range, 36-108 cm(3)) irradiated with a reference dose of 28 Gy. In the assessment of the skin and subcutaneous toxicity, the RTOG late radiation morbidity scoring system was applied. The radiosensitivity of the cultured fibroblasts was determined by clonogenic assay to check whether individual radiosensitivity played a role in the development and course of radiation-induced side-effects. RESULTS: The median follow-up was 12 years (range, 10-15 years). The population of the final study (34 cases) comprised all survivors with tumor-free breasts (27 cases) and patients with breasts erroneously ablated/excised for misinterpreted radiation-induced sequelae (7 patients). A total of 97% of the cohort (33/34) had grade > or =2, and 59% (20/34) had grade > or =3 radiation-induced toxicity. By the end of the follow-up, 85% of the patients experienced Grade > or =2 telangiectasis and 41% had Grade 3 telangiectasis. Eighty-eight percent had fibrosis of some form, and 35% had grade > or =3 fibrosis. Forty-one percent of the cohort displayed fat necrosis, which was always accompanied by Grade > or =3 fibrosis or telangiectasis. The cosmetic results were poor in 50% (17/34) of the patients. The radiosensitivity of the fibroblasts was increased in only 2/24 patients (8% of the investigated cases, in agreement with data published for the general population). Comparisons of our fibrosis prevalence data with those of others allowed an estimate of 0.47 h(-1) for the rate of recovery of DNA damage in the fibroblasts. CONCLUSIONS: Interstitial (60)Co BT of the breast tumor bed alone with a limited CTV (median, 72 cm(3)) and a total dose of 28 Gy is associated with a high rate (59%) of grade > or =3 radiation-induced toxicity and a high rate (50%) of poor cosmetic outcome at the end of a median follow-up of 12 years. A relatively high BT dose rate (1.3-2.8 Gy/h) applied during a short overall treatment time (10-22 h) and a possible geographic miss (close to skin implantation) might have contributed to the development of these sequelae.

• PET identifies transitional metabolic change in the spinal cord following a subthreshold dose of irradiation.

  Authors: Olga Esik, Miklós Emri, Szabolcs Szakáll, Hans Herzog, Géza Sáfrány, Erzsébet Lengyel, András Boér, Gabriella Liszkay, Lajos Trón, Zsolt Lengyel, Imre Repa

  Pathology oncology research : POR. 02/2004; 10(1):42-6.

  Positron emission tomographic (PET) investigations were performed to obtain in vivo information on symptomless radiation-induced pathological changes in the human spinal cord. PET investigations werePositron emission tomographic (PET) investigations were performed to obtain in vivo information on symptomless radiation-induced pathological changes in the human spinal cord. PET investigations were carried out prior to radiotherapy and during the regular follow-up in an early hypopharyngeal cancer patient (the spinal cord was irradiated with a biologically effective dose of 80 Gy2), with [18F]fluorodeoxyglucose (FDG), [11C]methionine and [15O]butanol as tracers; radiosensitivity and electroneuronographic (ENG) studies were also performed. A very low background FDG accumulation (mean standardized uptake values, i.e. SUV: 0.84) was observed in the spinal cord before the initiation of radiotherapy. An increased FDG uptake was measured 2 months after the completion of radiotherapy (mean SUV: 1.69), followed by a fall-off, as measured 7 months later (mean SUV: 1.21). By 44 months after completion of irradiation, the FDG accumulation in the irradiated segments of the spinal cord had decreased to a level very close to the initial value (mean SUV: 1.11). The simultaneous [15O]butanol uptake results demonstrated a set of perfusion changes similar to those observed in connection with the FDG accumulation. The patient exhibited an extremely low [11C]methionine uptake within the irradiated and the nonirradiated spinal cord during the clinical course. She has not had any neurological symptoms, and the results of central ENG measurements before radiotherapy and 2 months following its completion proved normal. Radiobiological investigations did not reveal unequivocal signs of an increased radiosensitivity. A transitory increased spinal cord FDG uptake following radiotherapy may be related to the posttherapeutic mild inflammatory and regenerative processes. The normal [11C]methionine accumulation observed is strong evidence against intensive cell proliferation. The high degree of normalization of the temporarily increased FDG uptake of the irradiated spinal cord segments by 44 months is in good agreement with the results of monkey studies, which demonstrated a nearly complete recovery from radiation-induced spinal cord injury.

• Comparative pharmacological studies on the A2 adenosine receptor agonist 5'-n-ethyl-carboxamidoadenosine and its F19 isotope labelled derivative.

  Authors: Bálint Rubovszky, A József Szentmiklósi, Teréz Márián, Agnes Cseppento, Rudolf Gesztelyi, Andrea Székely, Fruzsina Fórizs, Rezso Gáspár, Lajos Trón, Zoltán Krasznai

  Journal of pharmacological sciences. 12/2003; 93(3):356-63.

  Adenosine receptors are expressed in various mammalian tissues where they mediate the effects of adenosine on cellular functions through a number of signalling mechanisms. 18F-NECA is theAdenosine receptors are expressed in various mammalian tissues where they mediate the effects of adenosine on cellular functions through a number of signalling mechanisms. 18F-NECA is the positron-emitting derivative of the A(2)-receptor agonist NECA (5'-n-ethyl-carboxamidoadenosine) and is a radioligand for PET imaging of adenosine receptors. Contractility and relaxation studies were performed on guinea pig atrial myocardium, pulmonary artery, and thoracic aorta to compare the pharmacological effects of NECA and F-NECA (a non-emitting derivative) on tissues. Furthermore, the effect of NECA and F-NECA on the potassium conductance was investigated in DDT1 MF-2 smooth muscle cells with the patch-clamp technique. Both NECA and F-NECA reduced the contractile force in atrial myocardium and evoked phasic contraction in pulmonary artery (A(1) adenosine-receptor-mediated actions) in a dose dependent manner; however, the apparent affinity was lower for F-NECA. No difference was found in relaxation induced by these compounds in 1 microM noradrenaline-precontracted aorta and pulmonary artery (in the presence of DPCPX, an A(1) adenosine receptor antagonist, tissue containing A(2B) adenosine receptors). NECA (5 microM) and F-NECA (5 microM) also decreased the peak current and accelerated activation and inactivation properties of the potassium channels, but F-NECA was less effective. These results suggest that while NECA and F-NECA are equivalent agonists of vascular A(2B) receptors, they mediate different changes of some parameters. When evaluating the data obtained by the use of radiolabelled ligands, one has to take into consideration the possible physiological effects of the ligands besides its binding properties to tissues.

• [Effect of imatinib treatment of gastrointestinal stromal tumors]

  Authors: Sándor Eckhardt, Zsuzsanna Pápai, György Bodoky, József Horti, Karin Tamás, Tünde Nagy, Zsolt Orosz, Zoltán Sápi, Mária Gödény, Klára Jakab, Olga Esik, Lajos Trón, István Besznyák

  Orvosi hetilap. 12/2003; 144(45):2207-12.

  INTRODUCTION: Advanced malignant gastrointestinal stromal tumours are practically resistant to further radio- or chemotherapy. These tumours are characterized by the presence of C-KIT (aINTRODUCTION: Advanced malignant gastrointestinal stromal tumours are practically resistant to further radio- or chemotherapy. These tumours are characterized by the presence of C-KIT (a transmembrane tyrosin kinase) mutation which can be specified by CD117 expression. Imatinib (2-fenilaminopirimidine) is a selective inhibitor of the mutated C-KIT. AIM: The purpose of our study was to determine the potential antitumour effect of imatinib in patients with gastrointestinal stroma tumour patients. MATERIALS AND METHODS: An open, non-randomized trial was performed involving 38 patients each of which had received/metastatic disease associated with CD117 positivity. Consecutively daily doses of 400-600 mg imatinib was administered orally to the patients. The evaluation was carried out on 37 patients in a form of an interim analysis. RESULTS: After a 3-18 months observation period 1 complete, 19 partial remissions and 10 static diseases could be registered (78%), in association of only grade 1-2 toxicity. CONCLUSIONS: The imatinib treatment improved the quality of life of the patients with gastrointestinal stroma tumour and their life expectancy became considerably prolonged. Further follow-up of the patients as well as design of a prospective, randomized trial on a larger patient material is urgently needed.

• Increased metabolic activity in the spinal cord of patients with long-standing Lhermitte's sign.

  Authors: Olga Esik, Tibor Csere, Klára Stefanits, Szabolcs Szakáll, Zsolt Lengyel, Géza Sáfrány, Katalin Vönöczky, Erzsébet Lengyel, Judit Olajos, Gábor Bajzik, Lajos Trón

  Strahlentherapie und Onkologie : Organ der Deutschen Röntgengesellschaft ... [et al]. 11/2003; 179(10):690-3.

  PURPOSE: To investigate the pathophysiology of the radiation-induced, chronic Lhermitte's sign (LS) on the basis of long-standing case histories with partial functional recovery. PATIENTS ANDPURPOSE: To investigate the pathophysiology of the radiation-induced, chronic Lhermitte's sign (LS) on the basis of long-standing case histories with partial functional recovery. PATIENTS AND METHODS: As radiotherapy in two nasopharyngeal cancer patients, a biologically effective dose (BED) of 103.8 Gy(2) (case 1) and 94.8 Gy(2) (case 2) was delivered to the cervical spinal cord. Neurologic signs relating to the irradiated spinal cord segments developed after 2 months (case 1) and 5 years (case 2), with radiation-induced damage equivalent to grade 3 (case 1) and grade 2 (case 2) toxicity (Common Toxicity Criteria, Version 2.0). The clinical status improved to grade 2 (case 1) and grade 1 (case 2). Positron emission tomography (PET) and fibroblast clonogen assay were applied 25 and 7 years postirradiation, respectively, to characterize this rare clinical picture. RESULTS: PET demonstrated increased [(18)F]fluorodeoxyglucose (FDG) accumulation and [(15)O]butanol perfusion, but negligible [(11)C]methionine uptake in the irradiated spinal cord segments in both patients. In clonogenic assays, fibroblasts from case 1 displayed much higher radiation sensitivity than in healthy controls, while in case 2 the fibroblasts sensitivity was normal. CONCLUSIONS: These data suggests a close direct relationship between regional perfusion and metabolism of the spinal cord, similarly as in the brain. The postirradiation recovery may be related to energy-demanding conduction, explaining the increased metabolism and perfusion. The increased radiosensitivity and higher spinal cord BED may have contributed to the more severe sequelae in case 1.