Biodistribution and pharmacokinetics of [89Zr]-anti-VEGF mAbs using PET in glioblastoma rat models.

INTRODUCTION: Glioblastomas present intensive angiogenesis, thus anti-Vascular Endothelial Growth Factor (VEGF) antibodies (mAbs) have been proposed as promising therapies. However, the results of clinical trials reported moderate toxicity and limited effectiveness. This study evaluates the in vivo pharmacokinetics and biodistribution of these mAbs in a growing model of glioblastoma in rats using Positron Emission Tomography (PET). MATERIAL: &Methods: mAbs were radiolabeled with zirconium-89. Four days after the model induction, animals were injected with 2.33 ± 1.3 MBq of [89Zr]-DFO-bevacizumab (n = 8) or 2.35 ± 0.26 MBq of [89Zr]-DFO-aflibercept (n = 6). PETs were performed at 0H, 48H, 168H, 240H, and 336H post-injection. Tumor induction was confirmed using [18F]-Fluorodeoxyglucose-PET and immunohistochemistry. Radiotracer uptake was estimated in all pre-defined Volumes-of-Interest. RESULTS: Anti-VEGF mAbs showed 100 % Radiochemical-Purity. [89Zr]-DFO-bevacizumab showed a significantly higher bioavailability in whole-blood. A significant increase in the tumor uptake was detectable at 168H PET with [89Zr]-DFO-bevacizumab meanwhile with [89Zr]-DFO-aflibercept it was only detectable at 336H. [89Zr]-DFO-bevacizumab tumor uptake was significantly higher than that of [89Zr]-DFO-aflibercept in all the scans. Tumor induction was confirmed in all animal models. CONCLUSION: MAbs detect VEGF-expression in glioblastoma models. Tumors were earlier targeted by Bevacizumab. The lower blood availability of aflibercept resulted in a lower tumor uptake than bevacizumab in all the scans.

Fetal and maternal Doppler adaptation to maternal exercise during pregnancy: a randomized controlled trial.

BACKGROUND: Regular and supervised exercise during pregnancy is worldwide recommended due to its proven benefits, but, during exercise, maternal blood flow is redirected from the viscera to the muscles and how fetal wellbeing may be affected by this redistribution is still not well known. OBJECTIVE: To analyze the longitudinal effect of a supervised moderate physical exercise program during pregnancy on uteroplacental and fetal Doppler parameters. METHODS: This is a planned secondary analysis of an randomized controlled trial (RCT), performed at Hospital Universitario de Torrejón, Madrid, Spain, including 124 women randomized from 12+0 to 15+6 weeks of gestation to exercise vs. control group. Fetal umbilical artery (UA), middle cerebral artery, and uterine artery pulsatility index (PI), were longitudinally collected by Doppler ultrasound assessment throughout gestation, and derived cerebroplacental ratio (normalized by z-score), and maternal mean PI in the uterine arteries (normalized by multiplies of the median). Obstetric appointments were scheduled at 12 (baseline, 12+0 to 13+5), 20 (19+0 to 24+2), 28 (26+3 to 31+3) and 35 weeks (32+6 to 38+6) of gestation. Generalized estimating equations were adjusted to assess longitudinal changes in the Doppler measurements according to the randomization group. RESULTS: No significant differences in the fetal or maternal Doppler measurements were found at any of the different checkup time points studied. The only variable that consistently affected the Doppler standardized values was gestational age at the time of assessment. The evolution of the UA PI z-score during the pregnancy was different in the two study groups, with a higher z-score in the exercise group at 20 weeks and a subsequent decrease until delivery while in the control group it remained stable at around zero. CONCLUSIONS: A regular supervised moderate exercise program during pregnancy does not deteriorate fetal or maternal ultrasound Doppler parameters along the pregnancy, suggesting that the fetal well-being is not compromised by the exercise intervention. Fetal UA PI z-score decreases during pregnancy to lower levels in the exercise group compared with the control group.

FINDRISC Modified for Latin America as a Screening Tool for Persons with Impaired Glucose Metabolism in Ciudad Bolívar, Venezuela.

OBJECTIVE: The Finnish Diabetes Risk Score (FINDRISC) includes anthropometric, metabolic, and lifestyle factors that predict type 2 diabetes mellitus. The objective of this study was to evaluate the FINDRISC modified for Latin America (LA-FINDRISC) as a screening tool for persons with impaired glucose metabolism in Ciudad Bolívar, Venezuela. METHODS: Subjects aged between 18 and 70 years of both sexes without known diabetes were invited to participate. After informed consent, they were screened with the LA-FINDRISC questionnaire and then given an oral glucose tolerance test, using the American Diabetes Association criteria for diagnosis. To obtain the cutoff point of LA-FINDRISC for predicting impaired glucose regulation, a receiver operating characteristic curve was constructed. RESULTS: A total of 200 subjects were evaluated, 64.5% female, with a mean age of 35.20 ± 13.84 years. Of these, 158 (79%) did not present with carbohydrate metabolism disorder, while 42 (21%) did. Age (p = 0.0001), body mass index (p = 0.011), and waist circumference (p = 0.031) were significantly higher in subjects with impaired glucose regulation when compared to those without it. There were a significantly greater number of sedentary (p = 0.039) and hypertensive subjects (p = 0.0001), as well as those with a history of glucose >100 mg/dL (p = 0.0001), in the impaired glucose metabolism group. A cutoff LA-FINDRISC of 14 points predicted a high risk of impaired glucose regulation with a sensitivity of 45.2% and a specificity of 89.9%. CONCLUSION: A LA-FINDRISC >14 points had low sensitivity but high specificity for predicting carbohydrate metabolism disorders in this group of patients from Ciudad Bolívar.