Darstellung von Mikrogliaaktivierung und Glukoseverbrauch in einem Maus Modell für Morbus Alzheimer

In Alzheimer´s disease (AD), persistent microglial activation as sign of chronic neuroinflammation contributes to disease progression. Our study aimed to in vivo visualize and quantify microglial activation in 13- to 15-month-old AD mice using [11C]-(R)-PK11195 and positron emission tomography (PET). We attempted to modulate neuroinflammation by subjecting the animals to an anti-inflammatory treatment with pioglitazone (5-weeks’ treatment, 5-week wash-out period). [11C]-(R)-PK11195 distribution volume values in AD mice were significantly higher compared with control mice after the wash-out period at 15 months, which was supported by immunohistochemistry data. However, [11C]-(R)-PK11195 μPET could not demonstrate genotype- or treatment-dependent differences in the 13- to 14 month-old animals, suggesting that microglial activation in AD mice at this age and disease stage is too mild to be detected by this imaging method.Im Verlauf des Morbus Alzheimer unterhält eine persistierende Aktivierung der Mikroglia als Ausdruck einer chronischen Entzündung wesentlich das Voranschreiten dieser Erkrankung. Ziel unserer Untersuchung war die nicht-invasive Darstellung und Quantifizierung von Mikroglia-Aktivität im Gehirn von 13- bis 15-Monate alten Alzheimer-Mäusen mittels [11C]-(R)-PK11195 und Positronen-Emissions-Tomographie (PET). Weiterhin versuchten wir durch eine anti-inflammatorische Behandlung mit dem Wirkstoff Pioglitazon (5 Wochen Therapie, 5 Wochen Auswasch-Phase) die Neuro-Inflammation zu modulieren. Nach der Auswasch-Phase war das [11C]-(R)-PK11195 Verteilungsvolumen in 15-Monate alte Alzheimertieren signifikant höher als in Kontrolltieren. Dieses Ergebnis konnte auch immunhistochemisch bestätigt werden. [11C]-(R)-PK11195 μPET konnte aber keine genotypischen oder durch die Behandlung bedingten Unterschiede in den 13- oder 14-Monate alten Tieren darstellen. Diese Ergebnissen legen nahe, daß die Mikroglia-Aktivität in Alzheimermäusen dieses Alters und Krankheitsstadiums zu schwach ist, um mit dieser Bildgebungsmethode detektiert werden zu können

Intraoperative fluorescence imaging with aminolevulinic acid detects grossly occult breast cancer: a phase II randomized controlled trial

Abstract Background Re-excision due to positive margins following breast-conserving surgery (BCS) negatively affects patient outcomes and healthcare costs. The inability to visualize margin involvement is a significant challenge in BCS. 5-Aminolevulinic acid hydrochloride (5-ALA HCl), a non-fluorescent oral prodrug, causes intracellular accumulation of fluorescent porphyrins in cancer cells. This single-center Phase II randomized controlled trial evaluated the safety, feasibility, and diagnostic accuracy of a prototype handheld fluorescence imaging device plus 5-ALA for intraoperative visualization of invasive breast carcinomas during BCS. Methods Fifty-four patients were enrolled and randomized to receive no 5-ALA or oral 5-ALA HCl (15 or 30 mg/kg). Forty-five patients (n = 15/group) were included in the analysis. Fluorescence imaging of the excised surgical specimen was performed, and biopsies were collected from within and outside the clinically demarcated tumor border of the gross specimen for blinded histopathology. Results In the absence of 5-ALA, tissue autofluorescence imaging lacked tumor-specific fluorescent contrast. Both 5-ALA doses caused bright red tumor fluorescence, with improved visualization of tumor contrasted against normal tissue autofluorescence. In the 15 mg/kg 5-ALA group, the positive predictive value (PPV) for detecting breast cancer inside and outside the grossly demarcated tumor border was 100.0% and 55.6%, respectively. In the 30 mg/kg 5-ALA group, the PPV was 100.0% and 50.0% inside and outside the demarcated tumor border, respectively. No adverse events were observed, and clinical feasibility of this imaging device-5-ALA combination approach was confirmed. Conclusions This is the first known clinical report of visualization of 5-ALA-induced fluorescence in invasive breast carcinoma using a real-time handheld intraoperative fluorescence imaging device. Trial registration Clinicaltrials.gov identifier NCT01837225 . Registered 23 April 2013