Mekanisme Reaksi Asam Borat Dengan Produk Radiolisis Akibat Radiasi Sinar- Pada Temperatur 25oc

MEKANISME REAKSI ASAM BORAT DENGAN PRODUK RADIOLISIS AKIBAT RADIASI SINAR- PADA TEMPERATUR 25OC. Telah dilakukan simulasi yang bertujuan untuk memahami mekanisme reaksi antara asam borat (H3BO3) yang ditambahkan kedalam air pendingin primer PWR dengan produk radiolisis akibat radiasi dengan sinar- pada temperatur 25oC. Simulasi dilakukan dengan menggunakan perangkat lunak ‘Facsimile\u27 yang berbasis kinetika reaksi yang berkelanjutan. Sebagai masukan adalah set reaksi kimia yang terdiri dari 61 jenis reaksi dengan konstanta kecepatan reaksinya, nilai-G spesi radiolisis akibat radiasi sinar-, laju dosis 10 dan 104 Gy/s, konsentrasi awal oksigen yang berhubungan dengan sistem aerasi (0,25M), deaerasi dan konsentrasi asam borat hingga konsentrasi 1M. Luaran di program berupa seri Perubahan konsentrasi vs waktu iradiasi. Data luaran kemudian diolah menggunakan perangkat pembuat grafik ‘Origin\u27. Validasi dilakukan dengan membandingkannya dengan hasil simulasi sebelumnya. Hasil validasi menunjukkan perbedaan yang tidak signifikan, sehingga diputuskan bahwa set reaksi sekarang adalah valid. Penambahan asam borat menekan konsentrasi oksigen secara signifikan. Hubungan kenaikan logaritmik penambahan konsentrasi H3BO3 vs produk oksigen menunjukkan hubungan linear yang menurun. Dari hasil simulasi dapat dipahami bahwa penambahan H3BO3 tidak hanya mengatur reaktivitas neutron pada temperatur 25oC tetapi juga memberikan imbas positif didalam menekan konsentrasi produk oksigen yang memegang peran penting di dalam proses korosi

Pharmacokinetic Modeling of ( R)-[ 11 C]verapamil to measure the P-Glycoprotein function in nonhuman primates

(R)-[11C]verapamil is a radiotracer widely used for the evaluation of the P-glycoprotein (P-gp) function at the blood-brain barrier (BBB). Several studies have evaluated the pharmacokinetics of (R)-[11C]verapamil in rats and humans under different conditions. However, to the best of our knowledge, the pharmacokinetics of (R)-[11C]verapamil have not yet been evaluated in nonhuman primates. Our study aims to establish (R)-[11C]verapamil as a reference P-gp tracer for comparison of a newly developed P-gp positron emission tomography (PET) tracer in a species close to humans. Therefore, the study assesses the kinetics of (R)-[11C]verapamil and evaluates the effect of scan duration and P-gp inhibition on estimated pharmacokinetic parameters. Three nonhuman primates underwent two dynamic 91 min PET scans with arterial blood sampling, one at baseline and another after inhibition of the P-gp function. The (R)-[11C]verapamil data were analyzed using 1-tissue compartment model (1-TCM) and 2-tissue compartment model fits using plasma-corrected for polar radio-metabolites or non-corrected for radio-metabolites as an input function and with various scan durations (10, 20, 30, 60, and 91 min). The preferred model was chosen according to the Akaike information criterion and the standard errors (SE %) of the estimated parameters. 1-TCM was selected as the model of choice to analyze the (R)-[11C]verapamil data at baseline and after inhibition and for all scan durations tested. The volume of distribution (VT) and the efflux constant k2 estimations were affected by the evaluated scan durations, whereas the influx constant K1 estimations remained relatively constant. After P-gp inhibition (tariquidar, 8 mg/kg), in a 91 min scan duration, the whole-brain VT increased significantly up to 208% (p < 0.001) and K1 up to 159% (p < 0.001) compared with baseline scans. The k2 values decreased significantly after P-gp inhibition in all the scan durations except for the 91 min scans. This study suggests the use of K1, calculated with 1-TCM and using short PET scans (10 to 30 min), as a suitable parameter to measure the P-gp function at the BBB of nonhuman primates

Evaluation of [C-11]CB184 for imaging and quantification of TSPO overexpression in a rat model of herpes encephalitis

PURPOSE: Evaluation of translocator protein (TSPO) overexpression is considered an attractive research tool for monitoring neuroinflammation in several neurological and psychiatric disorders. [11C]PK11195 PET imaging has been widely used for this purpose. However, it has a low sensitivity and a poor signal-to-noise ratio. For these reasons, [11C]CB184 was evaluated as a potentially more sensitive PET tracer. METHODS: A model of herpes simplex encephalitis (HSE) was induced in male Wistar rats. On day 6 or 7 after virus inoculation, [11C]CB184 PET scans were acquired followed by ex vivo evaluation of biodistribution. In addition, [11C]CB184 and [11C]PK11195 PET scans with arterial blood sampling were acquired to generate input for pharmacokinetic modelling. Differences between the saline-treated control group and the virus-treated HSE group were explored using volumes of interest and voxel-based analysis. RESULTS: The biodistribution study showed significantly higher [11C]CB184 uptake in the amygdala, olfactory bulb, medulla, pons and striatum (p < 0.05) in HSE rats than in control rats, and the voxel-based analysis showed higher bilateral uptake in the pons and medulla (p < 0.05, corrected at the cluster level). A high correlation was found between tracer uptake in the biodistribution study and on the PET scans (p < 0.001, r2 = 0.71). Pretreatment with 5 mg/kg of unlabelled PK11195 effectively reduced (p < 0.001) [11C]CB184 uptake in the whole brain. Both, [11C]CB184 and [11C]PK11195, showed similar amounts of metabolites in plasma, and the binding potential (BPND) was not significantly different between the HSE rats and the control rats. In HSE rats BPND for [11C]CB184 was significantly higher (p < 0.05) in the amygdala, hypothalamus, medulla, pons and septum than in control rats, whereas higher uptake of [11C]PK11195 was only detected in the medulla. CONCLUSION: [11C]CB184 showed nonspecific binding to healthy tissue comparable to that observed for [11C]PK11195, but it displayed significantly higher specific binding in those brain regions affected by the HSE. Our results suggest that [11C]CB184 PET is a good alternative for imaging of neuroinflammatory processes

Pharmacokinetic Modeling of [ 18 F]MC225 for Quantification of the P-Glycoprotein Function at the Blood-Brain Barrier in Non-Human Primates with PET

[18F]MC225 has been developed as a weak substrate of P-glycoprotein (P-gp) aimed to measure changes in the P-gp function at the blood–brain barrier with positron emission tomography. This study evaluates [18F]MC225 kinetics in non-human primates and investigates the effect of both scan duration and P-gp inhibition. Three rhesus monkeys underwent two 91-min dynamic scans with blood sampling at baseline and after P-gp inhibition (8 mg/kg tariquidar). Data were analyzed using the 1-tissue compartment model (1-TCM) and 2-tissue compartment model (2-TCM) fits using metabolite-corrected plasma as the input function and for various scan durations (10, 20, 30, 60, and 91 min). The preferred model was chosen according to the Akaike information criterion and the standard errors (%) of the estimated parameters. For the 91-min scan duration, the influx constant K1 increased by 40.7% and the volume of distribution (VT) by 30.4% after P-gp inhibition, while the efflux constant k2 did not change significantly. Similar changes were found for all evaluated scan durations. K1 did not depend on scan duration (10 min—K1 = 0.2191 vs 91 min—K1 = 0.2258), while VT and k2 did. A scan duration of 10 min seems sufficient to properly evaluate the P-gp function using K1 obtained with 1-TCM. For the 91-min scan, VT and K1 can be estimated with a 2-TCM, and both parameters can be used to assess P-gp function

Head-to-head comparison of (R)-[11C]verapamil and [18F]MC225 in non-human primates, tracers for measuring P-glycoprotein function

Purpose P-glycoprotein (P-gp) function is altered in several brain disorders; thus, it is of interest to monitor the P-gp function in vivo using PET. (R)-[11C]verapamil is considered the gold standard tracer to measure the P-gp function; however, it presents some drawbacks that limit its use. New P-gp tracers have been developed with improved properties, such as [18F]MC225. This study compares the characteristics of (R)-[11C]verapamil and [18F]MC225 in the same subjects. Methods: Three non-human primates underwent 4 PET scans: 2 with (R)[11C]verapamil and 2 with [18F]MC225, at baseline and after P-gp inhibition. The 30-min PET data were analyzed using 1-Tissue Compartment Model (1-TCM) and metabolite corrected plasma as input function. Tracer kinetic parameters at baseline and after inhibition were compared. Regional differences and simplified methods to quantify the P-gp function were also assessed. Results At baseline, [18F]MC225 VT values were higher, and k2 values were lower than those of (R)-[11C]verapamil, whereas K1 values were not significantly different. After inhibition, VT values of the 2 tracers were similar; however, (R)-[11C]verapamil K1 and k2 values were higher than those of [18F]MC225. Significant regional differences between tracers were found at baseline, which disappeared after inhibition. The positive slope of the SUV-TAC was positively correlated to the K1 and VT of both tracers. Conclusion [18F]MC225 and (R)-[11C]verapamil show comparable sensitivity to measure the P-gp function in non-humanprimates. Moreover, this study highlights the 30-min VT as the best parameter to measure decreases in the P-gp function with both tracers. [18F]MC225 may become the first radiofluorinated tracer able to measure decreases and increases in the P-gp function due to its higher baseline VT

Highlight selection of radiochemistry and radiopharmacy developments by editorial board (January-June 2020)

BackgroundThe Editorial Board of EJNMMI Radiopharmacy and Chemistry releases a biyearly highlight commentary to describe trends in the field.ResultsThis commentary of highlights has resulted in 19 different topics selected by each member of the Editorial Board addressing a variety of aspects ranging from novel radiochemistry to first in man application of novel radiopharmaceuticals.ConclusionTrends in radiochemistry and radiopharmacy are highlighted demonstrating the progress in the research field being the scope of EJNMMI Radiopharmacy and Chemistry

Evaluation of P-glycoprotein function at the blood-brain barrier using [F-18]MC225-PET

P-glycoprotein (P-gp) is an ATP-dependent efflux transporter located at the blood–brain barrier (BBB), involved in the transport of a variety of neurotoxic substances out of the brain. Alterations in P-gp function play an essential role in the pathophysiological mechanisms underlying neurodegenerative disorders

Electrophysiologic Studies and Radiofrequency Catheter Ablation of Ectopic Atrial Tachycardia in Children

Ectopic atrial tachycardia (EAT) often resists medical therapy, making radiofrequency catheter ablation (RFCA) the preferred treatment. This study reviewed the records of 35 patients who underwent electrophysiologic studies (EPS) and 39 RFCA procedures for EAT during a 10-year period. Of the 35 patients, 10 (28%) presented with decreased ventricular function and tachycardia-induced cardiomyopathy (TIC). The EAT originated on the right atrial side in 19 patients (54%) and on the left atrial side in the remaining 16 patients (46%). The right atrial sites included the right atrial appendage (RAA) (n = 9, 25%), the tricuspid annulus (n = 7, 20%), and the crista terminalis (n = 3). The left atrial sites included the left atrial appendage (LAA) (n = 6, 17%), the pulmonary veins (n = 5, 14%), the mitral annulus (n = 3), and the posterior wall of the left atrium (n = 2). The mechanism of all EAT probably is automaticity. All EATs could be abolished using RFCA. Follow-up data were available for all patients 2 to 8 years after RFCA. All 35 patients remained recurrence free, and ventricular function improved for all 10 patients with TIC. The origin of EAT in children differed from its origin in adults. The authors conclude that RFCA is a safe and effective treatment option for children with refractory EAT and should be considered early in the course of their illness