Positron Emission Tomography in Tumor Diagnosis and Treatment Follow-Up

The technique of positron emission tomography (PET) is described. PET is an in vivo imaging and quantitative technique which allows the visualization of various functional and biochemical parameters. PET is a tracer technique in which bioactive tracer substances are labelled with short-lived positron emitting radionuclides. The most important of these are ¹⁵O, ¹³N, ¹¹C and ¹⁸F with decay times ranging from 2 min to 2 h. The radiolabeled substance is injected intravenously and the distribution, uptake and binding are registered externally with the PET camera using of the order of 4 000 small detectors. The camera produces simultaneously 15 tomographic slices in which the absolute concentration of the tracer substance can be measured. Using a dynamic imaging sequence starting after the injection of the tracer, the dynamics of the tracer uptake is recorded and can be used to deduce functional parameters, such as perfusion flow, tracer distribution, binding to receptor or enzyme systems, etc. depending on the choice of tracer substance. The great versatility of PET and its potential of direct noninvasive study of tumor function will make it a very important clinical and research tool in oncology. With the choice of substances selective for a certain aspect of a tumor's biochemistry the potential opens for a better diagnosis, improved differential diagnosis and, especially with the use of metabolic tracers, an improved possibility to evaluate the response to treatment.     

Modeling spheroid growth, PET tracer uptake, and treatment effects of the Hsp90 inhibitor NVP-AUY922.

For a PET agent to be successful as a biomarker in early clinical trials of new anticancer agents, some conditions need to be fulfilled: the selected tracer should show a response that is related to the antitumoral effects, the quantitative value of this response should be interpretable to the antitumoral action, and the timing of the PET scan should be optimized to action of the drug. These conditions are not necessarily known at the start of a drug-development program and need to be explored. We proposed a translational imaging activity in which experiments in spheroids and later in xenografts are coupled to modeling of growth inhibition and to the related changes in the kinetics of PET tracers and other biomarkers. In addition, we demonstrated how this information can be used for planning clinical trials. METHODS: The first part of this concept is illustrated in a spheroid model with BT474 breast cancer cells treated with the heat shock protein 90 (Hsp90) inhibitor NVP-AUY922. The growth-inhibitory effect after a pulse treatment with the drug was measured with digital image analysis to determine effects on volume with high accuracy. The growth-inhibitory effect was described mathematically by a combined E(max) and time course model fitted to the data. The model was then used to simulate a once-per-week treatment; in these experiments the uptake of the PET tracers (18)F-FDG and 3'-deoxy-3'-(18)F-fluorothymidine ((18)F-FLT) was determined at different doses and different time points. RESULTS: A drug exposure of 2 h followed by washout of the drug from the culture medium generated growth inhibition that was maximal at the earliest time point of 1 d and decreased exponentially with time during 10-12 d. The uptake of (18)F-FDG per viable tumor volume was minimally affected by the treatment, whereas the (18)F-FLT uptake decreased in correlation with the growth inhibition. CONCLUSION: The study suggests a prolonged action of the Hsp90 inhibitor that supports a once-per-week schedule. (18)F-FLT is a suitable tracer for the monitoring of effect, and the (18)F-FLT PET study might be performed within 3 d after dosing.     

Logics and Logistics of Community Intervention Against Osteoporosis: An Evidence Basis

Under designations like small areas action research and intervention, directed ‘ground-up’ health promotion and prevention in the population form an important part of the ongoing medical systems development. There is recent evidence of the success of community intervention against cardiovascular disease. In osteoporosis, however, there is still a lack of conclusive data on both the logics and logistics of such an approach. Since 1988, a county health policy program has been formulated and implemented in Östergötland, Sweden, following the principles and guidelines of the WHO HFA 2000 declaration. Vadstena (n ? 7,600) was chosen for a local and generalizable osteoporosis prevention project mediated by the primary care organization by means of health promotion and education in the community. In the present report we emphasize that community intervention is an important new advancement of the medical systems, where the basic research questions include operational and management aspects as equally vital and measurable requisites and results as other performance and outcome variables. We found that a community intervention trial against osteoporosis is both motivated and feasible and in this report wish to provide evidence on these crucial issues of logics and logistics.     

Prediction of Posttreatment Drinking Outcome in a 2-Year Out-Patient Alcoholic Treatment Program. A Follow-up Study

Fifty alcoholics who attended a 2-year out-patient treatment program with standardized evaluations every third month were followed-up 2 years after completion of the program. One patient refused to be followed-up and four were dead. Corroboration was available in 78% of the cases. The number of abuse days from the second half-year of therapy and forward was strongly related to the number of abuse days during the follow-up period as were ratings both of drinking goal fulfillment and fulfillment of other treatment goals at termination of the treatment period. On the contrary initial characteristics and background data as well as the number of abuse days during the first half-year were not related to number of abuse days during the follow-up period. Our findings indicate that improvement during long term out-patient treatment for alcoholism is stable during the following 2 years with a socially stable sample.     

Effects of intravenous contrast media on cortical and medullary blood flow in the rat kidney

The effect of slow intravenous infusion of contrast medium (CM) (1600 mg I/kg body weight) on cortical blood flow (BF) and medullary BF in rat kidneys was investigated by laser-Doppler flowmetry on either renal cortex or exposed renal papillas (inner medulla). The effect on cortical BF was evaluated after infusion of either ioxaglate, iohexol, or ioxithalamate. Mannitol and Ringer's solution were used as control substances. The effect on medullary BF was examined after infusion of either ioxaglate, iohexol, iopamidol, ioxithalamate, or mannitol. BF was measured continuously during a 30-minute control period and a 60-minute experimental period, starting with the CM infusion. Cortical BF was unchanged in the ioxaglate group and significantly increased in the iohexol, ioxithalamate, and mannitol groups (P less than .05). Medullary BF was moderately increased in the ioxaglate group (P less than .05) but moderately decreased in the groups that received iohexol, iopamidol, ioxithalamate, or mannitol (P less than .05). The reduction in medullary BF following infusion of the ratio 3.0 nonionic CM and of the ratio 1.5 ionic CM might be one contributory mechanism to the pathogenesis of CM nephropathy, especially in the presence of microangiopathy in the kidney.     

Effect of stimulation of the lateral hypothalamus on the correlation of neuron spike activity in the rabbit neocortex

Cross-correlation and autocorrelation histograms were constructed with the aim of studying correlated spike activity of neurons in the visual and sensorimotor regions of both hemispheres of the rabbit brain before and after stimulation of the right and left lateral hypothalamic regions, which generates food-motivated responses. Stimulation of the left hypothalamus produced larger rearrangements in correlated neuron firing than stimulation of the right hypothalamus. Stimulation of the left hypothalamus, unlike that of the right hypothalamus, was followed by significant increases in the numbers of pairs of left hemisphere neocortical neurons with linked activity, and also induced the sequential firing of neurons in a particular defined order: sensorimotor cortex cells fired first, followed by visual cortex neurons after delays of up to 120 msec. It is concluded that cortical interhemisphere asymmetry in conditions of hunger is associated with nonuniform functioning of the right and left lateral hypothalamic regions. Institute of Higher Nervous Activity and Neurophysiology, Russian Academy of Sciences, Moscow. Translated from Fiziologicheskii Zhurnal Vysshei Nervnoi Deyatel'nosti, Vol. 46, No. 6, pp. 1068–1075, November–December, 1996.