Biomedical subjects

Mats Bergström

Publications and source records attributed to Mats Bergström.

43 records · Page 3Linked to original sources

PubMed2002

Quantitative imaging and correction for cascade gamma radiation of 76Br with 2D and 3D PET.

Several positron emitting nuclides with applications in PET, such as 76Br, 124I, 110In and 86Y, also emit gamma radiation in their decays. Measured coincidences between annihilation photons and this cascade gamma radiation are essentially true coincidences and the standard PET corrections do not account for them. We investigated the performance of 76Br in 2D and 3D PET, the effect of the gamma radiation emitted by 76Br on quantitative accuracy and the distribution of cascade gamma radiation coincidences in 2D and 3D PET sinograms. A correction method for cascade gamma radiation coincidences was implemented and evaluated. Count rate linearity was affected by the gamma radiation from the 76Br decay. Spatial resolution and sphere recovery were slightly worse for 76Br compared to 18F. Correction for cascade gamma radiation coincidences by subtraction of a linear projection tail fit improved total correction accuracy to similar values as for positron-only emitters such as 18F, and improved image contrast significantly.

Bromine Radioisotopes↗

PubMed2002

Dopaminergic effects after chronic treatment with nandrolone visualized in rat brain by positron emission tomography.

Anabolic-androgenic steroids (AAS) have recently been shown to induce neurochemical alterations in areas of the male rat CNS related to behavioural changes that have been observed among AAS misusers. In the present study, positron emission tomography (PET) is suggested as a suitable in vivo method in order to visualize the density of the dopamine transporter ([11C]-FE-beta-CIT) as well as the dopamine D1-like ([11C]-(+)-SCH23390) and the D2-like receptors ([11C]-raclopride) in the male rat brain. Chronic treatment with the AAS nandrolone decanoate (15 mg/kg/day for 14 days) caused an up-regulation of the binding potential of the dopamine transporter in the striatum.

Anabolic Agents↗

PubMed2002

Effect of traumatic brain injury and nitrone radical scavengers on relative changes in regional cerebral blood flow and glucose uptake in rats.

Changes in regional cerebral blood flow (rCBF) and glucose metabolism are commonly associated with traumatic brain injury (TBI). Reactive oxygen species (ROS) have been implicated as key contributors to the secondary injury process after TBI. Here, pretreatment with the nitrone radical scavengers (alpha-phenyl-N-tert-butyl nitrone (PBN) or its sulfonated analogue sodium 2-sulfophenyl-N-tert-butyl nitrone (S-PBN) were used as tools to study the effects of ROS on rCBF and glucose metabolism after moderate (2.4-2.6 atm) lateral fluid percussion injury (FPI) in rats. S-PBN has a half-life in plasma of 9 min and does not penetrate the blood-brain barrier (BBB). In contrast, PBN has a half-life of 3 h and readily penetrates the BBB. Regional cerebral blood flow (rCBF) and glucose metabolism was estimated by using (99m)Tc-HMPAO and [(18)F]Fluoro-2-deoxyglucose (FDG) autoradiography, respectively, at 42 min (n = 37) and 12 h (n = 34) after the injury. Regions of interest were the parietal cortex and hippocampus bilaterally. As expected, FPI produced an early (42-min) hypoperfusion in ipsilateral cortex and an increase in glucose metabolism in both cortex and hippocampus, giving way to a state of hypoperfusion and decreased glucose metabolism at 12 h postinjury. On the contralateral side, a hypoperfusion in the cortex and hippocampus was seen at 12 h only, but no significant changes in glucose metabolism. Both S-PBN and PBN attenuated the trauma-induced changes in rCBF and glucose metabolism. Thus, the early improvement in rCBF and glucose metabolism correlates with and may partly mediate the improved functional and morphological outcome after TBI in nitrone-treated rats.

Animals↗

PubMed2002

The role of PET in localization of neuroendocrine and adrenocortical tumors.

Positron emission tomography (PET) supplies a range of labeled compounds to be used for the characterization of tumor biochemistry. Some of these have proved to be of value for clinical diagnosis, treatment follow up, and clinical research. The first routinely used PET tracer in oncology, (18)F-labeled deoxyglucose (FDG), was successfully used for diagnosis of cancer, reflecting increased expression of glucose transporter in cancerous tissue. This tracer, however, usually does not show sufficient uptake in well-differentiated tumors such as neuroendocrine tumors. We developed a tracer more specific to neuroendocrine tumors-the serotonin precursor 5-hydroxytryptophan (5-HTP) labeled with (11)C-and demonstrated increased uptake and irreversible trapping of this tracer in carcinoid tumors. The uptake was so selective and the resolution was so high that we could detect more liver and lymph node metastases with PET than with CT or octreotide scintigraphy. To further improve the method, especially to reduce the high renal excretion of the tracer producing streaky artifacts in the area of interest, we introduced premedication by the decarboxylase inhibitor carbidopa, leading to a six-fold decreased renal excretion while the tumor uptake increased three-fold, hence improving the visualization of the tumors. (11)C-labeled l-DOPA was evaluated as an alternative tracer, especially for endocrine pancreatic tumors, which usually do not demonstrate enhanced urinary serotonin metabolites. However, only half of the EPTs, mainly functioning tumors, could be detected with l-DOPA. Instead 5-HTP seems to be a universal tracer for EPT and foregut carcinoids. With new, more sensitive PET cameras, larger field of view and procedures for whole-body coverage, the PET examination with 5-HTP is now routinely performed as reduced whole-body PET examinations with coverage of the thorax and abdomen. With this method we have been able to visualize small neuroendocrine lesions in the pancreas and thorax (e.g., ACTH-producing bronchial carcinoids) not detectable by any other method, including octreotide scintigraphy, MRI, and CT. Another tracer, the 11beta-hydroxylase inhibitor, metomidate labeled with (11)C, was developed to simplify diagnosis and follow-up of patients with incidentalomas. A large series of patients with incidentally found adrenal masses have been investigated and so far all lesions of adrenocortical origin have been easily identified because of exceedingly high uptake of (11)C-metomidate, whereas noncortical lesions showed very low uptake. In addition, adrenocortical cancer shows high uptake, suggesting that this PET tracer can be used for staging purposes.

5-Hydroxytryptophan↗

PubMed2002

Rat studies comparing 11C-FMAU, 18F-FLT, and 76Br-BFU as proliferation markers.

UNLABELLED: We analyzed and compared 1-(2'-deoxy-2'-fluoro-beta-D-arabinofuranosyl)-[methyl-(11)C]thymine ((11)C-FMAU), 3'-deoxy-3'-[(18)F]fluorothymidine ((18)F-FLT) and 1-(2'-deoxy-2'-fluoro-beta-D-arabinofuranosyl)-5-[(76)Br]bromouracil ((76)Br-BFU) with respect to tissue uptake, DNA incorporation, and excretion modulation in rats. The goal of the investigation was to evaluate the efficiency of the 3 nucleoside tracers as potential tracers for measuring proliferation. METHODS: Sprague-Dawley rats were divided into 3 groups and administered 5 MBq (11)C-FMAU, 1 MBq (18)F-FLT, or 2 MBq (76)Br-BFU. For each tracer, a subgroup was also administered 6 mg/kg cimetidine. The rats in the (11)C-FMAU group were killed at 5, 20, 40, 60, and 80 min after injection; the rats in the (18)F-FLT group were killed at 80 min and 2 and 4 h; and the rats in the (76)Br-BFU group were killed at 5, 20, 40, and 80 min and 2, 4, 6, and 24 h. Samples of blood, liver, kidney, spleen, and intestine were taken, and the radioactivity was measured. DNA separation was made in the samples of spleen, and the radioactivity in the DNA fraction was measured. RESULTS: Maximal uptake of radioactivity was seen in the spleen and intestine, organs with active DNA synthesis. The highest relative radioactivity uptake was at 60 min in the (11)C-FMAU groups and at 4 h in the (18)F-FLT group. In the (76)Br-BFU group, the uptake increased gradually during the observation period, and uptake of radioactivity increased markedly in rats receiving cimetidine. Cimetidine did not affect radioactivity uptake in the (11)C-FMAU or (18)F-FLT groups. The fraction of radioactivity in DNA was 78% in spleen at 60 min in the (11)C-FMAU group, 80% at 60 min and 97% at 4 h in the (76)Br-BFU group. The DNA-incorporation was only 2% in the (18)F-FLT group. CONCLUSION: (76)Br-BFU predominantly incorporates into DNA and has great potential as a PET tracer for the assessment of proliferation in vivo. (11)C-FMAU also may have potential as a proliferation marker, but the observation time is limited. (18)F-FLT does not incorporate into DNA and is therefore not a direct marker of proliferation.

Animals↗

PubMed2001

Use of 5-[(76)Br]bromo-2'-fluoro-2'-deoxyuridine as a ligand for tumour proliferation: validation in an animal tumour model.

Uncontrolled cell proliferation is one of the prominent features in cancer development. Precise tools are needed for determination of the proliferation rate before, during and after treatment, thereby permitting assessment of treatment efficacy. The purpose of this study was to validate the use of 5-[(76)Br]bromo-2'-fluoro-2'-deoxyuridine ((76)Br-BFU) as a proliferation marker in an animal tumour model. Comparison was made with 2-[(14)C]thymidine ((14)C-TdR) incorporation and the labelling index assessed by bromodeoxyuridine (BrdUrd-LI). Fibrosarcoma (NFSA)-bearing mice were used for all experiments. Gemcitabine (dFdC), a potent inhibitor of DNA synthesis, was used to modulate cell proliferation. dFdC was injected intraperitoneally at a dose of 0.5 mg/kg or 40 mg/kg to induce partial ( approximately 50%) or complete inhibition of DNA synthesis, respectively. (76)Br-BFU (0.5-3 MBq per animal), (14)C-TdR (37-74 kBq per animal) and cold BrdUrd (60 mg/kg) were injected intraperitoneally in combination or alone. Animals were sacrificed at various times after tracer administration, and tumour and small intestine were removed for determination of radioactivity in whole tissue and the DNA fraction, as well as for LI assessment by flow cytometry. Cimetidine (6 mg/kg) was used to decrease (76)Br-BFU elimination and increase its bioavailability. The fraction of radioactivity associated with DNA increased with the time interval between tracer injection and tissue removal. At 6 h after injection, for both tracers, more than 95% of the radioactivity in the tumours was associated with the DNA fraction and an excellent correlation was observed with the LI. Similar findings were observed in the small intestine. Under all experimental conditions, (76)Br-BFU uptake was 4-10 times lower than (14)C-TdR uptake. Co-injection of cimetidine resulted in a three- to fourfold increase in (76)Br-BFU incorporation without affecting the effect of dFdC on DNA synthesis. (76)Br-BFU is a potentially good tracer for the assessment of tumour proliferation. It has all the specifications required of a PET tracer for clinical use. One limitation to its use is the necessity of co-injecting cimetidine to increase its bioavailability and hence its sensitivity for PET detection.

Animals↗

PubMedDate not supplied

Autoradiography with positron emitting isotopes in positron emission tomography tracer discovery.

Rapid development of labeling chemistry and generation of new chemical entities for biologic interactions via combinatorial chemistry and high throughput screening gives great potential for the development of new positron emission tomography (PET) tracer candidates. It must, however, be realized that a large fraction of these candidates will fail to characterize the desired biochemistry in vivo due to undesirable properties that are not relevant to providing a specific signal in vitro. A full characterization of a PET tracer is a lengthy and expensive procedure, and it is necessary to establish confidence via a number of assays that a tracer will provide useful data in the target species (generally human). These assays should also serve as a background to choose or to reject a tracer at an early time point, conserving valuable resources and time. Autoradiography performed as an ex vivo binding technique or as ex vivo recording of in vivo tracer distribution are, in this respect, very important tools. Autoradiography binding methods allow a range of frozen tissues to be sectioned and incubated with the PET tracer, and with due caution and controls with selective blockade of binding, quantitative values can be obtained with respect to tracer binding and its regional distribution. The method is easy to learn and set up, and should be included in all PET research and development labs. Ex vivo autoradiography of selected organs or whole animals gives qualitative images of a tracer's distribution with high resolution and is especially valid for 18F-labeled tracers. When tracer administration is not limited by mass due to specific radioactivity, 11C-tracers can also be readily used. This method is attractive to use as a complement to small animal imaging due to its high resolution and anatomical correlate. Living slice autoradiography is a more cumbersome method, but has an advantage of utilizing live tissue that retains certain metabolic functions. The use of these different methods in the validation of tracers and for supplying complementary information is illustrated.

Animals↗