S. Maia

Initial evaluation in healthy humans of [18F]DPA-714, a potential PET biomarker for neuroinflammation

INTRODUCTION The translocator protein 18 kDa (TSPO), although minimally expressed in healthy brain, is up-regulated in pathological conditions, coinciding with microglial activation. It is thereby a suitable in vivo biomarker of neuroinflammation for detection, evaluation and therapeutic monitoring of brain diseases. We aimed to estimate the radiation dosimetry of the positron emission tomography (PET) TSPO radioligand [(18)F]DPA-714, and we evaluated in healthy volunteers its whole-body uptake and cerebral kinetics. METHODS Biodistribution data from mice were used for the prediction of radiation dosimetry. In human studies, a 90-min dynamic PET scan was performed in seven healthy volunteers after injection of [(18)F]DPA-714 (245±45 MBq). Arterial and venous samples were collected from two subjects, and two additional subjects were submitted to whole-body acquisition. Regions of interest were defined over cerebral structures to obtain mean time-activity curves and to estimate the distribution volume ratios by Logan graphical analysis, and over peripheral organs to obtain standard uptake values. RESULTS The effective dose estimated from biodistribution in mice was 17.2 μSv/MBq. Modeling of regional brain and plasma data showed good in vivo stability of [(18)F]DPA-714 in humans, with only 20% of blood metabolites 20 min postinjection (p.i.). Maximum cerebral uptake was observed 5 min p.i., followed by two decreasing phases: a rapid washout (5-30 min) followed by a slower phase for the remainder of PET acquisition. Whole-body images demonstrate high activity in the gallbladder, heart, spleen and kidneys. CONCLUSIONS This initial study in humans shows that [(18)F]DPA-714 is a promising PET radioligand with excellent in vivo stability and biodistribution, and acceptable effective dose estimation. Therefore, [(18)F]DPA-714 could provide a sensitive measure of neuroinflammatory changes in subsequent clinical investigations.

Longitudinal and parallel monitoring of neuroinflammation and neurodegeneration in a 6-hydroxydopamine rat model of Parkinson's disease

As neuroinflammatory processes are involved in the pathogenesis of Parkinsons disease (PD), we achieved the longitudinal evaluation of them in parallel with the modifications of dopaminergic function at several time‐points after 6‐hydroxydopamine (6‐OHDA) lesion in the rat mimicking an early stage of PD. After unilateral intrastriatal 6‐OHDA administration, we quantified the temporal evolution of the 18 kDa translocator protein (TSPO), TH‐immunoreactivity and dopamine transporters in the striatum and substantia nigra pars compacta (SNc) from 3‐ to 56‐days postlesion (dpl). Increased binding of TSPO ligands used, i.e., [3H]PK11195 and [125I]CLINDE, was observed in the lesioned striatum at 3, 7, and 14 dpl, followed by a progressive return to the basal level at 56 dpl. The binding profile in the SNc showed progressive binding beginning at 3 dpl, peaking at 14 dpl, and progressively decreasing until 56 dpl. In this model, the neuroinflammatory and neurodegenerative processes occurred concomitantly. The transitory occurrence of microglial activation could be involved in the lasting installation of dopaminergic neuron loss. Synapse, 2012.

Évaluation de l’irradiation du personnel de chirurgie gynécologique lors de la recherche du ganglion sentinelle. Y a-t-il un risque pour le chirurgien et son équipe ?

OBJECTIVE Assess the radiation exposure of surgical staff during sentinel node surgery in gynecology using a radiotracer, the (99m)Tc-microalbumin. MATERIALS AND METHODS A monocentric, prospective study was conducted during 3 months representing 40 sentinel node surgical procedures with different dosimetric measurements. Dosimeters were used to evaluate the whole body and the fingers radiation exposure for all exposed workers (surgeon, nurse and surgical assistant). Another dosimeter was used to estimate the atmospheric radiation level. The activity of (99m)Tc-microalbumin was 50.1±2.4MBq when the surgery was performed the same day and 90.4±3.2MBq when the surgery was performed the day after. RESULTS Radioactive doses received during each procedure by the surgeon, surgical assistant and nurse are 5, 3.75 and 0μSv for whole body exposure and 17.5, 15.6 and 16.2μSv for extremities respectively. Atmosphere dosimeter does not detect any radiation over this period. On average, 200 procedures are performed each year in our hospital by 7 surgeons. Surgeons radiation exposure remains below the threshold of 1mSv annual for whole body and 50mSv annual for fingers set for public by the International Commission on Radiological Protection. DISCUSSION AND CONCLUSIONS During sentinel node surgery radiation exposure of surgical staff is weak. Everyone, including the surgeon, receives a dose below the limits of the public radiation exposure. There is no need for special dosimetric monitoring or use radiation protective devices during the sentinel node surgery using (99m)Tc-microalbumin injection.

Article originalÉvaluation de l’irradiation du personnel de chirurgie gynécologique lors de la recherche du ganglion sentinelle. Y a-t-il un risque pour le chirurgien et son équipe ?Radiation exposure of surgical staff during sentinel node surgery. Is there a risk for the surgeon and his team?

OBJECTIVE Assess the radiation exposure of surgical staff during sentinel node surgery in gynecology using a radiotracer, the (99m)Tc-microalbumin. MATERIALS AND METHODS A monocentric, prospective study was conducted during 3 months representing 40 sentinel node surgical procedures with different dosimetric measurements. Dosimeters were used to evaluate the whole body and the fingers radiation exposure for all exposed workers (surgeon, nurse and surgical assistant). Another dosimeter was used to estimate the atmospheric radiation level. The activity of (99m)Tc-microalbumin was 50.1±2.4MBq when the surgery was performed the same day and 90.4±3.2MBq when the surgery was performed the day after. RESULTS Radioactive doses received during each procedure by the surgeon, surgical assistant and nurse are 5, 3.75 and 0μSv for whole body exposure and 17.5, 15.6 and 16.2μSv for extremities respectively. Atmosphere dosimeter does not detect any radiation over this period. On average, 200 procedures are performed each year in our hospital by 7 surgeons. Surgeons radiation exposure remains below the threshold of 1mSv annual for whole body and 50mSv annual for fingers set for public by the International Commission on Radiological Protection. DISCUSSION AND CONCLUSIONS During sentinel node surgery radiation exposure of surgical staff is weak. Everyone, including the surgeon, receives a dose below the limits of the public radiation exposure. There is no need for special dosimetric monitoring or use radiation protective devices during the sentinel node surgery using (99m)Tc-microalbumin injection.