Tomographie par émission de positons

vignette|Reconstruction tridimensionnelle de la distribution de glucose marqué au telle que mesurée par tomographie d'émission de positons. Outre l'accumulation normale du traceur dans le cœur, la vessie, les reins et le cerveau, des métastases hépatiques d'une tumeur colorectale sont clairement visibles dans la région abdominale de l'image.|382x382px La tomographie par émission de positons (TEP), également dénommée PET ou PET scan (pour « positron emission tomography » en anglais), est une méthode d' pratiquée par les spécialistes en médecine nucléaire qui permet de mesurer en trois dimensions une activité métabolique ou moléculaire d'un organe grâce aux émissions produites par les positons (positrons en anglais) issus d'un produit radioactif injecté au préalable. La TEP repose sur le principe général de la scintigraphie qui consiste à injecter un traceur dont on connaît le comportement et les propriétés biologiques pour obtenir une image du fonctionnement d'un organe ou la présen

Monitoring tumor response to radiation therapy with longitudinal and multimodal molecular imaging

Jessica Perez

Purpose: Metabolic changes induced by radiation therapy (RT) provide a biological measure of tumor response to treatment beyond anatomic changes. In this preclinical study we investigated these changes through longitudinal monitoring of tumor response to varying doses of RT with 18F-Fluorodeoxyglucose Positron Emission Tomography (FDG-PET) and Computed Tomography (CT), as well as bioluminescence imaging (BLI). We sought to establish the metabolic alterations in irradiated tumors at early timepoints following treatment. Materials & Methods: Human HT-29 colon carcinoma cells were inoculated subcutaneously on both sides of the back of nude mice. Tumors were grown for two or three weeks. One tumor per animal was treated with 10 or 20 Gy of RT on day 0. The first ten mice were imaged with both FDG-PET and CT on day -1, 1, 3, 9, and 14. The other 10 mice were imaged with BLI once a week during tumor growth and on the same days as the PET-CT study. These findings were correlated with histology. Results: At the beginning of treatment tumors exhibited low FDG uptake. The volume of the treated tumors (TT) determined by CT images, remained stable or decreased (for dose of 20 Gy), whereas the untreated tumors (UT) continued growing. Surprisingly, 9 days after RT, the FDG-uptake increased in the TT and remained low in the UT. We observed a clear decrease in BLI signal in TTs appearing also 9 days after RT. Conclusion: We have applied preclinical imaging and radiotherapy methods to study tumor response to treatment. The surprising rise in FDG uptake at day 9 after RT could be the result of several mechanisms including in inflammation, that still remains to be determined with immunohistochemistry. This study raises the possibility of FDG PET producing false negatives for early response. The preliminary data reported here will be used to establish future technical and biological approaches towards monitoring cancer therapies

2010

Development of novel tools for imaging of metabolic fluxes in vivo

Tamara Maric

Bioluminescent imaging is a powerful technique that enables imaging in living organisms with high sensitivity, low background signal, low cost and without the need for radioactivity. The emitted photons are produced in the oxidation reaction of luciferin catalyzed by luciferase. In the caged luciferin approach, the bioluminescent readout is used for measuring the activity of a specific biochemical process. Luciferin is caged in order to prevent catalysis by luciferase, and only when the cage is removed by a specific biochemical event of interest, luciferin is released and becomes a substrate of luciferase. Hence, emitted photons are proportional to the amount of free luciferin, thus allowing to monitor the dynamics of the investigated process. Recent progress in the development of bioorthogonal reactions enabled to answer several fundamental biological questions, improve clinical diagnosis, and to better evaluate therapy efficacy. For example, one of the most robust biorthogonal reactions is the Staudinger ligation, which occurs between a properly tuned azide and a phosphine. In this work, we have used the caged luciferin approach combined with the Staudinger ligation to monitor metabolite uptake in living animals. We have successfully applied this method for the monitoring uptake of two metabolites â glucose and nicotinamide riboside (NR). Glucose is a major source of energy for most living organisms and its aberrant uptake is linked to many pathological conditions. On the other hand, NR is a form of vitamin B3 and represents one of the salvageable NAD+ precursors. Low NAD+ level inside of cells is strongly linked to numerous metabolic and age-related disorders. Despite of their importance, in both cases our understanding of disease-associated glucose or NR flux is limited due to a lack of robust tools. To date, positron emission tomography (PET) imaging remains the gold standard for measuring glucose uptake and no optical tools exist for non-invasive longitudinal imaging of neither of the two metabolites in in vivo settings. Here we report the development of a novel bioluminescent glucose uptake probe (BiGluc) and bioluminescent NR uptake probe (BiNR) for real-time, non-invasive longitudinal imaging of glucose and NR absorption both in vitro and in vivo. The new imaging reagents enable a wide range of applications in the field of metabolism and drug development.

EPFL2020

MicroPET imaging of 5-HT1A receptors in rat brain: a test-retest [F-18]MPPF study

Purpose Earlier studies have shown that positron emission tomography (PET) imaging with the radioligand [F-18] MPPF allows for measuring the binding potential of serotonin 5-hydroxytryptamine(1A) (5-HT1A) receptors in different regions of animal and human brain, including that of 5-HT1A autoreceptors in the raphe nuclei. In the present study, we sought to determine if such data could be obtained in rat, with a microPET (R4, Concorde Microsystems).

Springer-Verlag2009