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Imaging of progenitor cells in tumor environments
Research Corner
Abstracts of Funded National Institutes of Health Grants The following abstracts of diagnostic radiology research and training grants funded by the National Institutes of Health (NIH) were awarded to principal investigators (PIs) whose primary appointments are in medical school departments of radiology. These abstracts are listed on the NIH Web page (http://www-commons.cit.nih.gov/crisp/) and are printed here verbatim. The grant identification number (eg, 1RO1AI12345-01) contains a three-digit activity code (in the previous example, RO1) that identifies a specific category of extramural activity. All current NIH activity code titles and definitions can be obtained at the NIH Web page http://silk.nih.gov/silk/brownbooks/actcod. IRG (Internal Review Group) refers to the study section that reviewed the application. ICD (Institute, Center, Division) refers to the NIH funding source. The abstracts of the funded grants are printed alphabetically by author according to the funding institute or center.
National Cancer Institute WASHINGTON UNIVERSITY SMALL ANIMAL IMAGING RESOURCE Grant Number: PI Name:
5R24CA083060-04 Ackerman, Joseph
Abstract: It is proposed to establish the Washington University Small Animal Imaging Resource (WUSAIR) to provide state-of-the-art facilities and infrastructure for magnetic resonance imaging (MRI) and positron emission tomography (PET) analysis of mice, rats and other small laboratory animals. Located in the heart of Washington University Medical Center in St. Louis, WUSAIR will combine instrumental and intellectual capabilities found at few other institutions. WUSAIR will serve a broad community of scientists non-expert in MRI or PET technology who have a pressing need for quantitative image analysis of small laboratory animal model systems. A particular focus will be on mice and rat models of cancer. WUSAIR will also continue research and development at the frontier of imaging technology in an effort to make the most powerful of the new imaging strategies available to its community of users. Purchase of new PET and/or MRI scanners is not requested herein. Indeed, Washington University has generously supported the recent acquisition of such equipment as part of its continuing and substantive commitment to basic biomedical research. Currently on site and fully operation in the Imaging Research Center are two Varian INOVA 4.7 T MRI/MRS small animal research scanners. A PET scanner dedicated to small animal research, the microPET, will be delivered and sited in the Clinical Sci-
922
ences Research Building early next year. These PET and MRI small animal research scanners will form the core instrumentation of WUSAIR. Thesaurus Terms: bioimaging/biomedical imaging, biomedical resource magnetic resonance imaging, positron emission tomography Animalia, laboratory mouse, laboratory rat
Institution:
Fiscal Year: Department: Project Start: Project End: ICD: IRG:
Washington University Lindell And Skinker Blvd St. Louis, MO 63130 2002 Radiology 01-Sep-1999 31-Aug-2004 National Cancer Institute ZCA1
IMAGING OF PROGENITOR CELLS IN TUMOR ENVIRONMENTS Grant Number: PI Name:
1R01CA096978-01 Allport, Jennifer
Abstract: Both stem cells and progenitor cells hold significant promise as cell-based therapies. These cells have the unique ability to undergo self-renewal and to differentiate into a variety of different cell types, allowing the continued delivery of therapy for a prolonged period. Added benefits include, the use of the patient’s own cells, highly controlled in vitro manipulation of these cells, and the ease of delivery. Little is known, however, regarding the behavior of these
ABSTRACTS OF NIH GRANTS
Academic Radiology, Vol 10, No 8, August 2003
progenitor cells in vivo, their specific recruitment to tumors and the magnitude of in vivo cell trafficking. Utilizing a number of in vitro and in vivo imaging approaches, this proposal seeks to 1) determine mechanistic aspects that mediate previously identified apparently selective recruitment of progenitor cells to tumors, and 2) quantitate recruitments for different cells types, tumors and tumor microenvironments with regard to the latter we have recently observed highly efficient homing and retention capabilities. We hypothesize that there exist unique tumor endothelium/progenitor cell interactions that mediate attachment, transmigration and differentiation of the former in tumors and in particular the tumor microvasculature through vasculogenesis. In preliminary feasibility studies we have developed a number of tools that will allow us to interrogate tumor endothelium/progenitor cell interactions in vitro and in vivo. These tools include 1) isolation and characterization of differentiated endothelial cells (murine heart, murine lung and murine Lewis Lung carcinoma derived endothelium) and a panel of progenitor cells (murine C17.2 neuronal progenitors, murine CD34⫹ hematopoietic stem cells and CD34⫹/Flk-1⫹ endothelial progenitors), 2) in vitro flow chambers, 3) methods for imaging progenitor cells in vivo by optical, nuclear and MR imaging methods and 4) methods for isolation of tumor homed cells for comparative genomic analysis. Together, these techniques, and the expertise of a number of collaborators, will provide a powerful approach in understanding the mechanisms that target progenitor cells to tumors. Understanding the mechanisms that mediate progenitor cell recruitment both at a cellular and a molecular level, along with the ability to manipulate these events directly and promote increased recruitment of progenitor cells to the target tumor will provide a springboard to rapidly improved and more specific cellbased therapies for the direct treatment of tumor. Thesaurus Terms: angiogenesis, cell cell interaction, cell migration, hematopoietic stem cell, neoplastic cell, vascular endothelium CD34 molecule, CD44 molecule, cell adhesion, cell differentiation, cell type, cytokine receptor, gene expression, integrin, luciferin monooxygenase, molecular film, neuron, selectin immunomagnetic separation, laboratory mouse, magnetic resonance imaging, polymerase chain reaction, radiotracer
Institution:
Fiscal Year: Department: Project Start: Project End: ICD: IRG:
Massachusetts General Hospital 55 Fruit St Boston, MA 02114 2002 01-Aug-2002 31-Jul-2005 National Cancer Institute RNM
BIOLOGICAL IMAGE GUIDED/ RESPIRATION GATED IMRT OF NSCLC Grant Number: PI Name:
2P01CA059017-110004 Amois, Howard
Abstract: Description (provided by applicant): Lung cancer remains the most common cause of cancer death in the US with over 150,000 deaths per year. Radiation therapy (RT) is the main curative modality for inoperable non-small cell lung cancer (NSCLC). This study addresses the poor local control rates of conventional RT, where treatment success is constrained by: 1. Limits on radiation doses due to radiation pneumonitis, and for patients receiving concurrent chemotherapy (ChT), esophagitis. 2. Respiration-induced tumor motion, requiring larger treatment fields and increased treatment toxicity. 3. Uncertainties in tumor definition due to limited sensitivity and accuracy of CT imaging. 4. Uncertainties in RT treatment delivery and inability to confirm daily treatment accuracy. Previous studies have demonstrated the advantages of 3-D Conformal RT (3DCRT) and deep inspiration breath hold for reducing treatment uncertainties and normal tissue toxicities. In this proposal, significantly advanced technologies will be joined in an integrated approach to RT of NSCLC. These new strategies are: 1. Inverse Treatment Planning and Intensity Modulated RT for improved conformal normal tissue avoidance. 2. Respiratory Gating to control breathing motion during imaging, simulation, and treatment. 3. Improved tumor detection and delineation by combining FDG-PET and CT imaging. 4. Improved treatment verification using electronic portal imaging and megavoltage cone beam imaging. These new technologies will provide unprecedented accuracy in identifying and targeting tumors, and in minimizing normal tissue toxicity, thus permitting higher treatment doses. Our proposed clinical study targets 3 groups of surgically unresectable patients for escalation to the following maximum doses: (1) 99Gy to ‘small’ tumors; (2) 90Gy to ‘large’ tumors for patients ineligible for ChT, or who have previously received ChT; (3) 80 Gy RT for patients receiving concurrent ChT. We hypothesis that this high technology approach will permit treatment to higher doses without increasing normal tissue toxicity, and improve local control. Thesaurus Terms: human therapy evaluation, imaging/visualization/scanning, neoplasm/cancer radiation therapy, radiation therapy dosage clinical trial phase I, clinical trial phase II/III/IV, medical complication, method development, nonsmall cell lung cancer, pulmonary respiration bioimaging/ biomedical imaging, clinical research, computed axial tomography, human subject, patient oriented research, positron emission tomography
Institution:
Sloan-Kettering Institute For Cancer Res New York, NY 10021
923
Abstracts of Funded National Institutes of Health Grants The following abstracts of diagnostic radiology research and training grants funded by the National Institutes of Health (NIH) were awarded to principal investigators (PIs) whose primary appointments are in medical school departments of radiology. These abstracts are listed on the NIH Web page (http://www-commons.cit.nih.gov/crisp/) and are printed here verbatim. The grant identification number (eg, 1RO1AI12345-01) contains a three-digit activity code (in the previous example, RO1) that identifies a specific category of extramural activity. All current NIH activity code titles and definitions can be obtained at the NIH Web page http://silk.nih.gov/silk/brownbooks/actcod. IRG (Internal Review Group) refers to the study section that reviewed the application. ICD (Institute, Center, Division) refers to the NIH funding source. The abstracts of the funded grants are printed alphabetically by author according to the funding institute or center.
National Cancer Institute WASHINGTON UNIVERSITY SMALL ANIMAL IMAGING RESOURCE Grant Number: PI Name:
5R24CA083060-04 Ackerman, Joseph
Abstract: It is proposed to establish the Washington University Small Animal Imaging Resource (WUSAIR) to provide state-of-the-art facilities and infrastructure for magnetic resonance imaging (MRI) and positron emission tomography (PET) analysis of mice, rats and other small laboratory animals. Located in the heart of Washington University Medical Center in St. Louis, WUSAIR will combine instrumental and intellectual capabilities found at few other institutions. WUSAIR will serve a broad community of scientists non-expert in MRI or PET technology who have a pressing need for quantitative image analysis of small laboratory animal model systems. A particular focus will be on mice and rat models of cancer. WUSAIR will also continue research and development at the frontier of imaging technology in an effort to make the most powerful of the new imaging strategies available to its community of users. Purchase of new PET and/or MRI scanners is not requested herein. Indeed, Washington University has generously supported the recent acquisition of such equipment as part of its continuing and substantive commitment to basic biomedical research. Currently on site and fully operation in the Imaging Research Center are two Varian INOVA 4.7 T MRI/MRS small animal research scanners. A PET scanner dedicated to small animal research, the microPET, will be delivered and sited in the Clinical Sci-
922
ences Research Building early next year. These PET and MRI small animal research scanners will form the core instrumentation of WUSAIR. Thesaurus Terms: bioimaging/biomedical imaging, biomedical resource magnetic resonance imaging, positron emission tomography Animalia, laboratory mouse, laboratory rat
Institution:
Fiscal Year: Department: Project Start: Project End: ICD: IRG:
Washington University Lindell And Skinker Blvd St. Louis, MO 63130 2002 Radiology 01-Sep-1999 31-Aug-2004 National Cancer Institute ZCA1
IMAGING OF PROGENITOR CELLS IN TUMOR ENVIRONMENTS Grant Number: PI Name:
1R01CA096978-01 Allport, Jennifer
Abstract: Both stem cells and progenitor cells hold significant promise as cell-based therapies. These cells have the unique ability to undergo self-renewal and to differentiate into a variety of different cell types, allowing the continued delivery of therapy for a prolonged period. Added benefits include, the use of the patient’s own cells, highly controlled in vitro manipulation of these cells, and the ease of delivery. Little is known, however, regarding the behavior of these
ABSTRACTS OF NIH GRANTS
Academic Radiology, Vol 10, No 8, August 2003
progenitor cells in vivo, their specific recruitment to tumors and the magnitude of in vivo cell trafficking. Utilizing a number of in vitro and in vivo imaging approaches, this proposal seeks to 1) determine mechanistic aspects that mediate previously identified apparently selective recruitment of progenitor cells to tumors, and 2) quantitate recruitments for different cells types, tumors and tumor microenvironments with regard to the latter we have recently observed highly efficient homing and retention capabilities. We hypothesize that there exist unique tumor endothelium/progenitor cell interactions that mediate attachment, transmigration and differentiation of the former in tumors and in particular the tumor microvasculature through vasculogenesis. In preliminary feasibility studies we have developed a number of tools that will allow us to interrogate tumor endothelium/progenitor cell interactions in vitro and in vivo. These tools include 1) isolation and characterization of differentiated endothelial cells (murine heart, murine lung and murine Lewis Lung carcinoma derived endothelium) and a panel of progenitor cells (murine C17.2 neuronal progenitors, murine CD34⫹ hematopoietic stem cells and CD34⫹/Flk-1⫹ endothelial progenitors), 2) in vitro flow chambers, 3) methods for imaging progenitor cells in vivo by optical, nuclear and MR imaging methods and 4) methods for isolation of tumor homed cells for comparative genomic analysis. Together, these techniques, and the expertise of a number of collaborators, will provide a powerful approach in understanding the mechanisms that target progenitor cells to tumors. Understanding the mechanisms that mediate progenitor cell recruitment both at a cellular and a molecular level, along with the ability to manipulate these events directly and promote increased recruitment of progenitor cells to the target tumor will provide a springboard to rapidly improved and more specific cellbased therapies for the direct treatment of tumor. Thesaurus Terms: angiogenesis, cell cell interaction, cell migration, hematopoietic stem cell, neoplastic cell, vascular endothelium CD34 molecule, CD44 molecule, cell adhesion, cell differentiation, cell type, cytokine receptor, gene expression, integrin, luciferin monooxygenase, molecular film, neuron, selectin immunomagnetic separation, laboratory mouse, magnetic resonance imaging, polymerase chain reaction, radiotracer
Institution:
Fiscal Year: Department: Project Start: Project End: ICD: IRG:
Massachusetts General Hospital 55 Fruit St Boston, MA 02114 2002 01-Aug-2002 31-Jul-2005 National Cancer Institute RNM
BIOLOGICAL IMAGE GUIDED/ RESPIRATION GATED IMRT OF NSCLC Grant Number: PI Name:
2P01CA059017-110004 Amois, Howard
Abstract: Description (provided by applicant): Lung cancer remains the most common cause of cancer death in the US with over 150,000 deaths per year. Radiation therapy (RT) is the main curative modality for inoperable non-small cell lung cancer (NSCLC). This study addresses the poor local control rates of conventional RT, where treatment success is constrained by: 1. Limits on radiation doses due to radiation pneumonitis, and for patients receiving concurrent chemotherapy (ChT), esophagitis. 2. Respiration-induced tumor motion, requiring larger treatment fields and increased treatment toxicity. 3. Uncertainties in tumor definition due to limited sensitivity and accuracy of CT imaging. 4. Uncertainties in RT treatment delivery and inability to confirm daily treatment accuracy. Previous studies have demonstrated the advantages of 3-D Conformal RT (3DCRT) and deep inspiration breath hold for reducing treatment uncertainties and normal tissue toxicities. In this proposal, significantly advanced technologies will be joined in an integrated approach to RT of NSCLC. These new strategies are: 1. Inverse Treatment Planning and Intensity Modulated RT for improved conformal normal tissue avoidance. 2. Respiratory Gating to control breathing motion during imaging, simulation, and treatment. 3. Improved tumor detection and delineation by combining FDG-PET and CT imaging. 4. Improved treatment verification using electronic portal imaging and megavoltage cone beam imaging. These new technologies will provide unprecedented accuracy in identifying and targeting tumors, and in minimizing normal tissue toxicity, thus permitting higher treatment doses. Our proposed clinical study targets 3 groups of surgically unresectable patients for escalation to the following maximum doses: (1) 99Gy to ‘small’ tumors; (2) 90Gy to ‘large’ tumors for patients ineligible for ChT, or who have previously received ChT; (3) 80 Gy RT for patients receiving concurrent ChT. We hypothesis that this high technology approach will permit treatment to higher doses without increasing normal tissue toxicity, and improve local control. Thesaurus Terms: human therapy evaluation, imaging/visualization/scanning, neoplasm/cancer radiation therapy, radiation therapy dosage clinical trial phase I, clinical trial phase II/III/IV, medical complication, method development, nonsmall cell lung cancer, pulmonary respiration bioimaging/ biomedical imaging, clinical research, computed axial tomography, human subject, patient oriented research, positron emission tomography
Institution:
Sloan-Kettering Institute For Cancer Res New York, NY 10021
923