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Biomedical subjects

M Bergström

Publications and source records attributed to M Bergström.

233 records · Page 13Linked to original sources
PubMedDate not supplied

PET study of methionine accumulation in glioma and normal brain tissue: competition with branched chain amino acids.

Five patients with glioma were examined with positron emission tomography using ([11C]methyl)-L-methionine. The study was repeated while the patient was being infused with branched chain amino acids (BCAA), 250 mumol/min. The accumulation rates of methionine in tumor tissue and in normal brain tissue were compared without and with the infusion of amino acids. Both tumor tissue and normal brain tissue showed a reduction in the methionine accumulation by 35% while the patient received the infusion. In one patient with a severe blood-tissue barrier disruption the tumor accumulation rate was unaffected. It is concluded that in gliomas without severe blood-tissue barrier disruption, the accumulation of methionine is governed by processes exhibiting similar properties regarding competition with BCAA as in normal brain tissue.

Amino Acids, Branched-Chain↗
PubMedDate not supplied

Amino acid distribution and metabolism in pituitary adenomas using positron emission tomography with D-[11C]methionine and L-[11C]methionine.

Four patients with hormonally inactive pituitary adenomas were examined with positron emission tomography (PET) after injection, during different examinations, of L-[methyl-11C]methionine and D-[methyl-11C]methionine, respectively. After the rapid distribution phase, the enantiomer L-[11C]methionine, which is metabolically active, showed a considerable continuous irreversible trapping attributed to amino acid metabolism. The stereoisomer D-[11C]methionine, which does not participate in protein synthesis, showed a rapid distribution within the whole adenoma tissue, with a distribution space on the order of 100%. A minimal irreversible trapping was observed which could be explained by technical factors. It is concluded that PET using the two enantiomers allows a separation of passive distribution and metabolism, and that L-[11C]methionine can be used for in vivo quantitative studies of amino acid metabolism of pituitary adenomas.

Adenoma↗
PubMedDate not supplied

Rapid decrease in amino acid metabolism in prolactin-secreting pituitary adenomas after bromocriptine treatment: a PET study.

Four patients with prolactin-secreting pituitary adenomas were examined with positron emission tomography using L-[11C]methionine to monitor the effect of dopamine agonist treatment on the amino acid metabolism in the tumors. Within the first few hours after intramuscular injection of bromocriptine retard (50 mg) the amino acid metabolism decreased by 40%. Two of the patients were reexamined 7 and 9 days later and showed a 70% reduction in the metabolism of the adenomas. This metabolic effect was later accompanied by significant tumor shrinkage in all adenomas. It is suggested that bromocriptine has a general and rapid effect on the protein synthesis of the prolactin-secreting pituitary adenoma cells.

Adenoma↗
PubMedDate not supplied

Positron emission tomography of cavernous haemangiomas of the brain.

Four cases with lesions suspected to be low-grade intracerebral tumours but later proved to be cavernous haemangiomas are described. The patients were examined with contrast enhanced CT and with positron emission tomography (PET). The lesions were partly calcified with a mild or no mass effect and a slight contrast enhancement at CT. There were signs of disrupture of the blood-lesion barrier also on radionuclide studies. PET with 11C-methionine and 11C-glucose showed a normal or decreased accumulation of the tracers. This combination of findings has not been encountered in intracranial tumours. As a comparison, one case of glioblastoma is described. In this patient, the CT findings suggested a cavernous haemangioma. However, PET showed a markedly increased accumulation of 11C-methionine, which is compatible with brain tumour but not with haemangioma.

Adult↗
PubMedDate not supplied

Stereotactic radiation therapy of intracranial lesions. Methodologic aspects.

A technique for stereotactic radiation therapy of cerebral tumours and arteriovenous malformations using a linear accelerator (6 MV photons) is proposed. Treatment relies on a fixation system that permits a precise use of the coordinates estimated at stereotactic angiography or stereotactic computed tomography. The field of treatment can be exactly outlined in the CT images during repeat examinations, thus facilitating the recognition of changes induced by radiation. The system also allows the extent of the arteriovenous malformation, as seen at angiography, to be accurately traced in the CT sections thus enabling evaluation of possible radiation damage to surrounding brain structures. The precision of the method as well as its hypothetical merits and disadvantages are discussed. The number of patients treated is still small and the follow-up time is too short in the majority of cases to allow definite conclusions. Examples of preliminary results are given.

Aged↗
PubMedDate not supplied

Uptake of 14C- and 11C-labeled glutamate, glutamine and aspartate in vitro and in vivo.

To explore their potential use as in vivo tracers, the uptake of the amino acids glutamine, glutamate and aspartate, labeled with 11C or 14C, was evaluated in tumor cell aggregates, in vivo in rats and a few pilot studies with positron emission tomography (PET) in patients. The uptake in aggregates increased linearly with time, and was competitively inhibited by the same amino acids. The uptake of 14C-glutamate in carcinoid cells (BON) was inhibited by cystine but not by aspartate, contrary to the result in neuroblastoma (LAN). 6-Diazo-oxy-L-norleucine (a glutamine analogue) and Substance P had different effect on the uptake of glutamate in different cells. The metabolic fate of 14C-glutamate was evaluated with protein separation and with HPLC. The in vivo distribution in rats showed the highest uptake of 11C-glutamine and 11C-glutamate in pancreas and kidney, and of 11C-aspartate in the lung. In the human studies with PET, pancreas had the highest uptake followed by kidney with 11C-glutamate, and followed by spleen with 11C-aspartate. A primary pancreas tumour and metastases in liver were difficult to identify except in one case.

2-Aminoadipic Acid↗
PubMedDate not supplied

In vitro PET evaluations in lung cancer cell lines.

UNLABELLED: One purpose of the study was to explore the PET tracer 11C-L-DOPA for the discrimination between small-cell lung cancer (SCLC) and non small-cell lung cancer (NSCLC). A further aim was to explore the potential antitumoral effects of 6-diazo-5-oxy-L-norleucine (DON) and the use of a PET proliferation marker for the evaluation. MATERIALS AND METHODS: Four lung cancer and one endocrine tumour cell line (BON) were cultured as monolayer. The uptake of 5-[76Br]-bromo-2-fluoro-deoxyuridine (76Br-BFU), [11C]-L-DOPA (11C-DOPA) and [18F]-fluorodeoxyglucose (18FDG) were evaluated. The effects of specific enzyme inhibitors affecting the DOPA metabolism were explored. The effect of DON on proliferation and uptake of 76Br-BFU were assessed. RESULTS: All cell types showed a measurable uptake of 11C-DORA, with slightly lower values in lung cancer. There were no clear differences between SCLC and NSCLC. The addition of COMT inhibitor induced a significantly increased uptake of the tracer in BON cells, but not in lung cancer cells. DON significantly reduced the proliferation in all cell lines. The 76Br-BFU uptake was reduced markedly in all cell lines during DOn treatment. CONCLUSION: 11C-DOPA failed to distinguish between SCLC and NSCLC. DON showed strong antiproliferative effects which might motivate renewed interest in this drug for clinical cancer treatment. PET with 76Br-BFU might be used for treatment evaluation.

Antibiotics, Antineoplastic↗
PubMedDate not supplied

Positron emission tomography compared with magnetic resonance imaging and computed tomography in supratentorial gliomas using multiple stereotactic biopsies as reference.

Ten patients with findings at computed tomography (CT) suggesting intracranial supratentorial glioma were investigated to compare the diagnostic efficacy of this technique with that of positron emission tomography (PET) using 11C-methionine and examinations with magnetic resonance (MR). The findings were related to histopathologic examination of serial stereotactic biopsies, which were guided by the appearance of the lesions on PET examination. To obtain corresponding slice orientation with the different examination techniques, an individually shaped helmet fixation was used. However, in 3 cases this fixation device could not be used for MR. Histopathologic diagnosis, obtained in all cases from multiple target stereotactic biopsies, included glioma in 9 patients and reactive gliosis in one case. A detailed comparison of the three imaging techniques and the findings at stereotactic biopsies was possible in 7 patients, while in 3 patients comparison with MR was less exact due to the patient's refusal to wear the helmet during this examination. MR was the most accurate method for outlining the total extent of a lesion, i.e. the tumor and the edema surrounding it. Four lesions had homogeneous signal characteristics and in 6 lesions two (or more) compartments could be distinguished with MR. In 5 cases the MR findings were in complete agreement with the histopathologic findings. However, a thorough correlation between signal characteristics and histology was not possible. Using PET the occurrence and the extent of tumor tissue was correctly predicted in 7 patients. The PET was normal in one case. Findings at CT were in agreement with the histopathologic diagnosis in 5 patients. MR was the most sensitive method for the detection of lesions.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMedDate not supplied

Comparison of the accumulation kinetics of L-(methyl-11C)-methionine and D-(methyl-11C)-methionine in brain tumors studied with positron emission tomography.

Five patients with glioma were examined with positron emission tomography after the administration of 11C-L-methionine and at a following day with 11C-D-methionine. The rates of accumulation of the tracers were determined in the tumor and in the normal brain tissue according to a graphical technique of Patlak et coll. The accumulation rates for L-methionine were on the average 2.4 times higher than those of D-methionine in the tumors. The corresponding ration for normal brain tissue was 2.3. It is concluded that in this group of tumors without obvious blood-tumor-barrier breakdown, a stereospecific process with similar properties as in the normal brain tissue, is responsible for the accumulation of the labelled methionine.

Astrocytoma↗
PubMedDate not supplied

Application of a kinetic model on the methionine accumulation in intracranial tumours studied with positron emission tomography.

Eleven patients were studied with positron emission tomography (PET) using 11C-methionine. They all had low-grade astrocytomas (Kernohan grade II). The PET studies were analyzed with a metabolic model to obtain values for the influx, the accumulation rate and the partition coefficient of methionine in normal and tumourous tissue. Seven of the tumours showed an increased accumulation of methionine as compared with normal tissue on the static PET scans and also had higher values as to the kinetic parameters. Four tumours had a methionine accumulation equal to or lower than that of normal tissue and the kinetic parameters were also lower. Application of the kinetic model did not aid significantly in the delineation of the tumours. There was a correlation between the three parameters indicating an adaptation of the transport of methionine to the regional metabolic demand. The accumulation rate for normal cortical tissue was 0.49 nmol/g/min, the influx 0.97 nmol/ml and the partition coefficient 0.45 ml/g. These values are considerably higher than those previously reported. The differences might be attributed to differences in the corrections introduced for i.a. the occurrence of labelled metabolites in serum. With the use of a kinetic model, more information about the tracer is utilized and gained compared with the previously used graphic approach.

Brain Neoplasms↗
PubMedDate not supplied

Positron emission tomography with 11C-methionine and computed tomography of intracranial tumours compared with histopathologic examination of multiple biopsies.

A selected group of 36 patients with suspected supratentorial gliomas were investigated with positron emission tomography (PET) using 11C-methionine and transmission computed tomography (CT) before and after intravenous injection of contrast medium. Every examination was performed with the head fixed in a plastic helmet and a baseplate to guarantee that the slice orientation was the same at examinations with the two modalities and over time. Guided by the examinations, multiple stereotactic biopsies were performed with the biopsy instrument mounted on the baseplate. Regional accumulation of methionine was compared with histology of the corresponding samples and with attenuation before and after injection of contrast medium as well as mass effect on CT. Typically, there was a low attenuating lesion with a slight mass effect on CT. There was an increased accumulation compared with normal brain tissue in 31 cases of tumours and ordinary or decreased accumulation in 3 cases of tumours. In 22 cases with increased accumulation of methionine the extension of the tumour judged by PET corresponded with that of histology. In 4 cases tumour cells were found outside the area with pathologic methionine uptake. In 5 patients there were areas with increased methionine accumulation where no tumour cells were found. In 22 cases PET using methionine was more accurate than CT in defining the tumour boundaries as determined from the histologic findings. Four groups of biopsy specimens with different amounts of methionine accumulation are described. The uptake in a single biopsy gives good but not exact information about the histology of the specimen.

Brain Neoplasms↗
PubMedDate not supplied

PET studies of glucose metabolism in patients with schizophrenia.

The hypothesis of abnormal patterns of metabolism in schizophrenia was examined in a series of six young patients with psychotic symptoms satisfying the research diagnostic criteria. After intravenous injection of 11C-glucose obtained through a photosynthetic process, the regional activity of 11C in brain was measured with a four-ring positron camera. Regions of interest were obtained from computed tomographic images. Each patient underwent a second positron emission tomographic examinations after 4-5 weeks of treatment with a neuroleptic drug. No evidence of a hypofrontal pattern was found, but after treatment there was a reduced frontal uptake on the left side compared with temporal regions. The left-right asymmetry in the lentiform nucleus was reduced after treatment.

Acute Disease↗
PubMedDate not supplied

Cerebrospinal fluid circulation: evaluation by single-photon and positron emission tomography.

Gamma camera cisternography after intrathecal administration of 111In-DTPA is a widely used and well established technique for studies of cerebrospinal fluid (CSF) circulation. The radiation dose from 111In, however, is a limiting factor that sometimes seriously affects the image quality and, hence, correct interpretation. This investigation was designed to assess the value of tomographic techniques for studies of CSF flow. Single-photon emission computed tomography (SPECT) was performed on 15 patients by means of the Karolinska Hospital rotating gamma camera system after injection of 111In-DTPA or 99mTc-DTPA. The combination of SPECT and 99mTc-DTPA proved to be a valuable technique. It permits a clear evaluation of the location of the isotope intracranially and its precise relation to the ventricles. Positron emission tomography (PET) applied after intrathecal administration of 68Ga-EDTA demonstrates that small amounts of radioactivity can be registered and that PET is a promising technique for the evaluation of CSF dynamics.

Cerebrospinal Fluid↗
PubMedDate not supplied

Leukotriene and 5-lipoxygenase inhibitor induced variations in thymidine uptake in a human glioma cell line cultured as monolayers or as multicellular spheroids.

Effects of exogenous leukotrienes and/or treatment with the 5-lipoxygenase inhibitor, AA-861, on the 3H-thymidine uptake were investigated in a human glioma cell line, U-343MGa, growing as monolayers or multicellular spheroids. The spheroids contained about four times more endogenous leukotrienes than the monolayers. Administration of 0.1 microM exogenous leukotriene D4 increased the 3H-thymidine uptake in the spheroids while it gave a decrease in the monolayers. Inhibition of 3H-thymidine uptake was induced in the spheroids by 10 microM AA-861 and this inhibition was only seen during the period at which central necrosis develops in the spheroids. This drug showed an inhibitory effect on monolayers one day after subculture but gave no measurable effect on the monolayers two days later. It seemed that AA-861 exerted an inhibitory action at culture conditions associated with "cellular stress" such as subculture (trypsinization) of monolayers and induction of necrosis in spheroids. Induction of "cellular stress" with heat or exposure to a Ca(2+)-ionophore also gave an inhibitory action of AA-861 and the inhibition could be counteracted by administration of exogenous B4 leukotrienes. The observed effects are probably related to the activation of the arachidonic acid cascade and indicate that leukotrienes in some way interact with "cellular stress" and induce acute changes in 3H-thymidine uptake. Further research is necessary to reveal the detailed molecular mechanisms.

Antineoplastic Agents↗
PubMedDate not supplied

Effect of 6-diazo-5-oxo-L-norleucine (DON) on human carcinoid tumor cell aggregates.

The induction of glutamine starvation has been suggested as a potential target for antitumoral treatment using inhibitors of amidotransferase, an enzyme which mediates the conversion of glutamate to glutamine. Using multicellular aggregates from tumor cell lines, the effect of treatment with a suggested glutamine antagonist, 6-diazo-5-axo-L-norleucine (DON), was investigated. As indicators of treatment response, three different parameters were measured: aggregate size, uptake of 14C-methionine and secretion of Chromogranin A. Of six cell types evaluated (carcinoid, glioma, neuroblastoma pancreas and bladder cancer), the largest inhibition of 14Cmethionine uptake, amounting to 60%, was found in the carcinoid cell line BON. In this cell line the maximum effect was reached already at 10 microM concentration. DON induced marked growth inhibition in the BON aggregates which lasted 3-4 weeks after which regrowth started. During this period the secretion of chromogranin and methionine uptake was also inhibited. These studies suggest that the neuroendocrine cell line BON is especially vulnerable to treatment by DON and show that strong inhibitory effects are found at concentrations lower than that achieved in patient blood in previous clinical trials.

2-Aminoadipic Acid↗
PubMedDate not supplied

PET with hydroxytryptophan as tracer in hormone-refractory prostatic adenocarcinoma: evaluation of decarboxylation in vivo.

Position emission tomography (PET) was performed on two patients with hormone-refractory prostatic adenocarcinoma in order to characterize the mechanism behind an earlier observed increased uptake of tracer hydroxytryptophan (5-HTP) in bone metastases. The osseous metastases were investigated with 5-hydroxytryptophan, radio-labelled with 11C in the carboxyl group (5-HTC), and with 5-HTP in order to elucidate in vivo the presence of hydroxytryptophan decarboxylation. An increased uptake, measured as standard uptake value (SUV), in the metastatic lesions was observed using 5-HTP. The uptake varied between lesions. Using 5-HTC a corresponding uptake was observed. The time-activity rates were similar. The congruence in uptake patterns between 5-HTP and 5-HTC in the investigated lesions, demonstrates that decarboxylation of 5-hydroxytryptophan to serotonin is not a dominant factor in the uptake. It was concluded that 5-HTC could be used in vivo to investigate the chemical event of decarboxylation of 5-hydroxytryptophan and provide information about characteristics in metastatic lesions.

5-Hydroxytryptophan↗