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Preclinical Evaluation of CD40-Directed Immunotherapy in B-Cell Lymphoma Using [<sup>18</sup>F]Fluorothymidine-PET

Advances in Molecular Imaging 2015年第2期5卷 17-28页

作者： nicolas graf Zhoulei Li Ken Herrmann Michaela Aichler Jolanta Slawska Axel Walch Christian Peschel Markus Schwaiger Andreas K. Buck Tobias Dechow Ulrich Keller III. Medical Department of Hematology and Medical Oncology Technische Universitat München Munich Germany Department of Nuclear Medicine Technische Universitat München Munich Germany Department of Nuclear Medicine Universitat Sklinikum Würzburg Würzburg Germany Institute of Pathology—Analytical Pathology Helmholtz Zentrum München Neuherberg Germany German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ) Heidelberg Germany

Background: Inhibition of the lymphoma surface antigen CD40 by the antagonistic CD40 antibody NVP-HCD122 (HCD122) demonstrates activity in various lymphoma subtypes. In this preclinical in vivo study we examined the suitability of positron emission tomography (PET) using the thymidine analogue 3’-deoxy-3’-[18F]fluorothymidine (FLT) for early response assessment upon HCD122 treatment in diffuse large B cell lymphoma (DLBCL). Methods: Immunodeficient mice bearing human DLBCL xenografts (SU-DHL-4) received weekly intraperitoneal injections of HCD122. Tumor growth was followed up until Day 14. Molecular imaging with FLT-PET was performed before (Day 0) and after start of therapy (Day 2 and Day 7). On Day 14 lymphoma xenografts were explanted for immunohistochemical analysis to correlate PET findings with CD40 surface expression on tumor tissue. Results: Treatment with HCD122 significantly delayed tumor growth resulting in a tumor growth inhibition of 45% on Day 14. Significant reduction of tumor-to-background ratio (TBR) of FLT-PET was seen in treated animals on Day 7 and preceded change of tumor volume, thus predicting therapy response to HCD122. Immunohistochemical analysis of xenografts revealed significantly higher CD40 expression on treated than on untreated tissue. Moreover, we found a significant correlation between CD40 expression and FLT-PET response for xenograft tumor treated with HCD122. Conclusions: Treatment of DLBCL with the antagonistic CD40 antibody HCD122 can be monitored with FLT-PET as early as seven days after commencement of therapy and seems to increase CD40 expression on tumor tissue.

关键词： CD40 Antibody FLT-PET Lymphoma Therapy Monitoring

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Diagnosis of Developmental Dysplasia of the Hip Using Sound Transmission in Neonates

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Health 2014年第18期6卷 2510-2516页

作者： nicolas Padilla-Raygoza Diana Medina-Alvarez Ma Laura Ruiz-Paloalto Teodoro Cordova-Fraga Modesto Antonio Sosa-Aquino Aaron Huetzin Perez-Olivas Department of Nursing and Obstetrics Division of Health Sciences and Engineering Campus Celaya Salvatierrra University of Guanajuato Celaya Mexico Department of Clinical Nursing Division of Health Sciences and Engineering Campus Celaya Salvatierrra University of Guanajuato Celaya Mexico Department of Engineering Physics Division of Engineering Science Campus Leon University of Guanajuato Leon Mexico

The developmental dysplasia of the hip disease is in 1% of newborns, and it is a risk factor for dislocation of the hip;only 1 from 7000 newborns develops dislocation of the hip. Newborns were selected from public and private hospitals in Celaya, Guanajuato. Parents were asked to sign informed consent. Clinical maneuvers were applied for diagnosis of developmental dysplasia of the hip, on three consecutive occasions, two by the same investigator and the third by a different observer: Ortolani, Barlow, Piston, Galeazzi, Peter Baden, the comparative sound transmission test, and comparative sound transmission with extension/flexion test were applied. The diagnosis was confirmed with ultrasound of hip, technique graf, I healthy hip, II functionally immature, III subluxation, and IV dislocation. Sample size was 8 affected hips and 56 healthy hips. Kappa for intra observer and inter observer reliability were measured;the validity was measured by sensitivity, specificity, positive and negative predictive values, using the ultrasound diagnosis as the gold standard. The sample consisted of 78 neonates hips with female’s predominance. With comparative sound transmission test was obtained Kappa intra observer 0.80, Kappa inter observer 0.93, sensitivity 45.45%, specificity 96.27%, positive predictive value 66.67% and negative predictive value 91.49%;with comparative sound transmission with extension/flexion, was 0.83, 0.92, 72.73%, 95.52%, 72.73%, and 95.52%, respectively. The tests compared the sound transmission help better diagnose developmental dysplasia disease of the hip.

关键词： Sound Transmission Newborns Developmental Dysplasia of Hip

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Validity and Reliability of a Measuring Device Based on Sound Transmission for Diagnosis of Hip Dysplasia in Newborns

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Advances in Bioscience and Biotechnology 2014年第10期5卷 831-837页

作者： nicolas Padilla-Raygoza Rosalina Diaz-Guerrero Ma. Laura Ruiz-Paloalto Teodoro Cordova-Fraga Modesto Antonio Sosa-Aquino Aaron Huetzin Perez-Olivas Department of Nursing and Obstetrics Division of Health Sciences and Engi-neering Campus Celaya Salvatierra University of Guanajuato Celaya Mexico Department of Clinical Nursing Division of Health Sciences and Engineering Campus Celaya Salvatierra University of Guanajuato Celaya Mexico Department of Physical Engineering Division of Sciences and Engineering Campus Leon University of Guanajuato Leon Mexico

Sound transmission has been used for diagnosis of hip dysplasia in newborns and infants with tunning fork and sthetoscope. The study aims to identify the validity of a device based on sound transmission. Male and female newborns from Celaya, Gto, ranging from 4 to 28-day-old were selected for the study. The sound transmission device was used both, in bilateral assessment (compared sound transmission) and on each hip separately (sound transmission with extension/flexion). In the first application if the sound is lower by a digit, there is a hip unhealthy. In the second application if the sound is increased by a digit, there is also an alteration of the hip. A hip ultrasound was applied using the graf technique as a gold standard. Sensitivity, specificity and predictive values were calculated to identify validity. The intra-observer and inter-observer Kappa Test was applied to identify reliability. The hips of 103 newborns were assessed, obtaining a sensitivity of 60.9%, and a specificity of 92%;it should be a positive predictive value of 51.9% and a negative predictive value of 95% for the compared sound transmission test. In the sound transmission test with extension/flexion, the values were 82.6%, 96.2%, 73.1% and 97.8% for sensitivity, specificity, positive predictive value and negative predictive value, respectively. The result of the intra-observer kappa was 0.80 and the inter-observer was 0.70 for the compared sound transmission. The intra-observer Kappa was 0.88 and the inter-observer was 0.78 for the compared sound transmission test with extension/flexion. The device for sound transmission is valid and reliable for the diagnosis of dysplastic development hip disease in newborns.

关键词： Validity Reliability Sound Transmission Dysplasia of the Hip

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