Insects in burned forests - forest protection and faunal conservation (preliminary results)

The beetle colonization of fire-damaged trees was studied in seven reserves, which were established in burned forests in south and central Sweden, following extensive forest fires in the summer of 1992. In the spring of 1993, burned pine trees displayed a large range in fire damage from virtually undamaged ones to trees killed by the fire. Spruces were more sensitive than pine, and few fire-damaged spruces had some green foliage left. The pine shoot beetle, Tomicus piniperda (Linnaeus) was the main colonizer of pine trees, occurring at all sites, but altogether in only one-third of the trees. On spruce, two bark beetles were common: Polygraphus poligraphus (Linnaeus) was found on nearly all sites and altogether on half of the trees, followed in abundance by Pityogenes chalcographus (Linnaeus). These common species were accompaniedby an assembly of bark and longhorn beetles, commonly occurring on fresh conifer timber. Most of the beetle species clearly preferred the dead or dying trees. However, the species mentioned above as well as Arhopalus rusticus (Linnaeus) also attacked trees with more than half of the foliage left. Three fire-favoured species were observed: Oxypteris (Melanophila) acuminata (Degeer), Sericoda (Agonum) quadripunctata (Degeer) and Pterostichus quadrifoveolatus (Letzner). Line surveys indicated little bark beetle dispersal from the burned areas into surrounding forests. Further studies are needed as the primary colonization of the burned trees was obviously not completed during this first year after the fire

A new, fast and semi-automated size determination method (SASDM) for studying multicellular tumor spheroids

BACKGROUND: Considering the width and importance of using Multicellular Tumor Spheroids (MTS) in oncology research, size determination of MTSs by an accurate and fast method is essential. In the present study an effective, fast and semi-automated method, SASDM, was developed to determinate the size of MTSs. The method was applied and tested in MTSs of three different cell-lines. Frozen section autoradiography and Hemotoxylin Eosin (H&E) staining was used for further confirmation. RESULTS: SASDM was shown to be effective, user-friendly, and time efficient, and to be more precise than the traditional methods and it was applicable for MTSs of different cell-lines. Furthermore, the results of image analysis showed high correspondence to the results of autoradiography and staining. CONCLUSION: The combination of assessment of metabolic condition and image analysis in MTSs provides a good model to evaluate the effect of various anti-cancer treatments

Blood-Brain Barrier Penetration of Zolmitriptan—Modelling of Positron Emission Tomography Data

Positron emissiontomography (PET) with the drug radiolabelled allows a direct measurement of brain or other organ kinetics, information which can be essential in drug development. Usually, however, a PET-tracer is administered intravenously (i.v.), whereas the therapeutic drug is mostly given orally or by a different route to the PET-tracer. In such cases, a recalculation is needed to make the PET data representative for the alternative administration route. To investigate the blood-brain barrier penetration of a drug (zolmitriptan) using dynamic PET and by PK modelling quantify the brain concentration of the drug after the nasal administration of a therapeutic dose. [11C]Zolmitriptan at tracer dose was administered as a short i.v. infusion and the brain tissue and venous blood kinetics of [11C]zolmitriptan was measured by PET in 7 healthy volunteers. One PET study was performed before and one 30min after the administration of 5mg zolmitriptan as nasal spray. At each of the instances, the brain radioactivity concentration after subtraction of the vascular component was determined up to 90min after administration and compared to venous plasma radioactivity concentration after correction for radiolabelled metabolites. Convolution methods were used to describe the relationship between arterial and venous tracer concentrations, respectively between brain and arterial tracer concentration. Finally, the impulse response functions derived from the PET studies were applied on plasma PK data to estimate the brain zolmitriptan concentration after a nasal administration of a therapeutic dose. The studies shows that the PET data on brain kinetics could well be described as the convolution of venous tracer kinetics with an impulse response including terms for arterial-to-venous plasma and arterial-to-brain impulse responses. Application of the PET derived impulse responses on the plasma PK from nasal administration demonstrated that brain PK of zolmitriptan increased with time, achieving about 0.5mg/ml at 30min and close to a maximum of 1.5mg/ml after 2hr. A significant brain concentration was observed already after 5min. The data support the notation of a rapid brain availability of zolmitriptan after nasal administratio

Synthesis of two potential NK1-receptor ligands using [1-11C]ethyl iodide and [1-11C]propyl iodide and initial PET-imaging

BACKGROUND: The previously validated NK(1)-receptor ligand [O-methyl-(11)C]GR205171 binds with a high affinity to the NK(1)-receptor and displays a slow dissociation from the receptor. Hence, it cannot be used in vivo for detecting concentration changes in substance P, the endogenous ligand for the NK(1)-receptor. A radioligand used for monitoring these changes has to enable displacement by the endogenous ligand and thus bind reversibly to the receptor. Small changes in the structure of a receptor ligand can lead to changes in binding characteristics and also in the ability to penetrate the blood-brain barrier. The aim of this study was to use carbon-11 labelled ethyl and propyl iodide with high specific radioactivity in the synthesis of two new and potentially reversible NK(1)-receptor ligands with chemical structures based on [O-methyl-(11)C]GR205171. METHODS: [1-(11)C]Ethyl and [1-(11)C]propyl iodide with specific radioactivities of 90 GBq/μmol and 270 GBq/μmol, respectively, were used in the synthesis of [O-methyl-(11)C]GR205171 analogues by alkylation of O-desmethyl GR205171. The brain uptake of the obtained (2S,3S)-N-(1-(2- [1-(11)C]ethoxy-5-(3-(trifluoromethyl)-4H-1,2,4-triazol-4-yl)phenyl)ethyl)-2-phenylpiperidin-3-amine (I) and (2S,3S)-2-phenyl-N-(1-(2- [1-(11)C]propoxy-5-(3-(trifluoromethyl)-4H-1,2,4-triazol-4-yl)phenyl)ethyl)piperidin-3-amine (II) was studied with PET in guinea pigs and rhesus monkeys and compared to the uptake of [O-methyl-(11)C]GR205171. RESULTS: All ligands had similar uptake distribution in the guinea pig brain. The PET-studies in rhesus monkeys showed that (II) had no specific binding in striatum. Ligand (I) had moderate specific binding compared to the [O-methyl-(11)C]GR205171. The ethyl analogue (I) displayed reversible binding characteristics contrary to the slow dissociation rate shown by [O-methyl-(11)C]GR205171. CONCLUSION: The propyl-analogue (II) cannot be used for detecting changes in NK(1)-ligand levels, while further studies should be performed with the ethyl-analogue (I)

Multicellular Tumour Spheroid as a model for evaluation of [(18)F]FDG as biomarker for breast cancer treatment monitoring

BACKGROUND: In order to explore a pre-clinical method to evaluate if [(18)F]FDG is valid for monitoring early response, we investigated the uptake of FDG in Multicellular tumour spheroids (MTS) without and with treatment with five routinely used chemotherapy agents in breast cancer. METHODS: The response to each anticancer treatment was evaluated by measurement of the [(18)F]FDG uptake and viable volume of the MTSs after 2 and 3 days of treatment. RESULTS: The effect of Paclitaxel and Docetaxel on [(18)F]FDG uptake per viable volume was more evident in BT474 (up to 55% decrease) than in MCF-7 (up to 25% decrease). Doxorubicin reduced the [(18)F]FDG uptake per viable volume more noticeable in MCF-7 (25%) than in BT474 MTSs. Tamoxifen reduced the [(18)F]FDG uptake per viable volume only in MCF-7 at the highest dose of 1 μM. No effect of Imatinib was observed. CONCLUSION: MTS was shown to be appropriate to investigate the potential of FDG-PET for early breast cancer treatment monitoring; the treatment effect can be observed before any tumour size changes occur. The combination of PET radiotracers and image analysis in MTS provides a good model to evaluate the relationship between tumour volume and the uptake of metabolic tracer before and after chemotherapy. This feature could be used for screening and selecting PET-tracers for early assessment of treatment response. In addition, this new method gives a possibility to assess quickly, and in vitro, a good preclinical profile of existing and newly developed anti-cancer drugs

Unidirectional Influx and Net Accumulation of PIB

The compound {N-methyl-[11C]}2-(4’-methylaminophenyl)-6-hydroxybenzothiazole, “PIB”, measured by positron emission tomography, has been demonstrated to image brain β-amyloid deposition in Alzheimer’s disease (AD). In the present study the benefit of measuring the PIB accumulation rate together with the unidirectional influx of PIB into the brain was investigated in healthy control subjects and patients with AD. In a monkey changes in the influx rate constant K1 of PIB closely followed changes in CBF, caused by alteration of PaCO2. In addition, K1 was high both in the monkey and in humans, suggesting that this parameter reflects CBF. Most AD patients studied showed clearly higher accumulation rate for PIB than the controls in cortical brain areas, while a few patients showed as low accumulation as the controls. K1 did not correlate with the accumulation rate, indicating that K1 for PIB provides extra information besides the accumulation rate