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 s...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.展开更多
Since the introduction of multimodal therapy regimens,the prognosis of esophageal cancer has improved.There is undoubtedly true for patients with surgically resected tumors in the case of a response to neoadjuvant che...Since the introduction of multimodal therapy regimens,the prognosis of esophageal cancer has improved.There is undoubtedly true for patients with surgically resected tumors in the case of a response to neoadjuvant chemotherapy or chemoradiation.Important conclusions can be drawn from this regarding the indication for perioperative therapies,the radicality of surgery,or the surgical indications.Thus,most of the current research in this f ield is aimed at the early identif ication of this subset of patients,at the beginning of,or even before,neoadjuvant treatment.Conventional staging tools have failed to predict responses to neoadjuvant therapy.However,molecular imaging methods,e.g.positron emission tomography(PET)-scans,have shown promising results in the early selection of responders and non-responders during the course of neoadjuvant therapy,allowing physicians to alter the treatment plan accordingly.Even more desirable is the identif ication of potential responders before the start of neoadjuvant therapy.Preliminary molecular data on biopsy specimens demonstrate the possibility of early response prediction in these patients.We present the current knowledge on response evaluation and prediction in esophageal cancer and draw conclusions for future clinical practice and studies in this review.展开更多
文摘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.
文摘Since the introduction of multimodal therapy regimens,the prognosis of esophageal cancer has improved.There is undoubtedly true for patients with surgically resected tumors in the case of a response to neoadjuvant chemotherapy or chemoradiation.Important conclusions can be drawn from this regarding the indication for perioperative therapies,the radicality of surgery,or the surgical indications.Thus,most of the current research in this f ield is aimed at the early identif ication of this subset of patients,at the beginning of,or even before,neoadjuvant treatment.Conventional staging tools have failed to predict responses to neoadjuvant therapy.However,molecular imaging methods,e.g.positron emission tomography(PET)-scans,have shown promising results in the early selection of responders and non-responders during the course of neoadjuvant therapy,allowing physicians to alter the treatment plan accordingly.Even more desirable is the identif ication of potential responders before the start of neoadjuvant therapy.Preliminary molecular data on biopsy specimens demonstrate the possibility of early response prediction in these patients.We present the current knowledge on response evaluation and prediction in esophageal cancer and draw conclusions for future clinical practice and studies in this review.
