Over the past two decades, epigenetic regulation has become a rapidly growing, highly innovative and influential field of biology and medicine. Protein acetylation and deacetylation, two key epigenetic regulatory mechanisms, are mediated by histone acetylase transferases (HATs) and histone deacetylases (HDACs), respectively. To date, the vast majority of studies on epigenetic regulation have been conducted in cell cultures and tissue samples using conventional methodologies of molecular and cellular biology, which contain inherent limitations for monitoring therapy and disease. Therefore, there is a growing need for novel, advanced methodologies that allow for non-invasive detection and monitoring of HDAC–mediated epigenetic regulatory processes in different organs and tissues. One such methodology is molecular imaging with positron emission tomography (PET), which allows for non-invasive visualization and quantification of spatial and temporal dynamics of expression-activity of various receptors and enzymes in different organs and tissues in norm and disease. The availability of selective substrates to various classes and isoforms of HDACs would enable the development of radiolabeled imaging agents for non-invasive in vivo PET imaging. Therefore, the aim of this work is to develop class- and/or isoform-selective radiolabeled substrates of HDACs, with particular emphasis on class III (sirtuins, SIRTs).
Herein, HDAC class IIa, SIRT1 and SIRT2-selective radiotracers have been developed and validated through in vitro and in vivo characterization. Two of these tracers, 18F-TFAHA for HDAC class IIa and and 2-[18F]PhAHA for SIRT1, have also been validated in a disease model demonstrating their utility in understanding epigenetic regulation in an aggressive form of brain cancer. The development of these targeted imaging agents may help develop new therapies for disease as well as methodologies for monitoring treatment effectiveness and disease progression.
","abstract_html":"<p>Over the past two decades, epigenetic regulation has become a rapidly growing, highly innovative and influential field of biology and medicine. Protein acetylation and deacetylation, two key epigenetic regulatory mechanisms, are mediated by histone acetylase transferases (HATs) and histone deacetylases (HDACs), respectively. To date, the vast majority of studies on epigenetic regulation have been conducted in cell cultures and tissue samples using conventional methodologies of molecular and cellular biology, which contain inherent limitations for monitoring therapy and disease. Therefore, there is a growing need for novel, advanced methodologies that allow for non-invasive detection and monitoring of HDAC–mediated epigenetic regulatory processes in different organs and tissues. One such methodology is molecular imaging with positron emission tomography (PET), which allows for non-invasive visualization and quantification of spatial and temporal dynamics of expression-activity of various receptors and enzymes in different organs and tissues in norm and disease. The availability of selective substrates to various classes and isoforms of HDACs would enable the development of radiolabeled imaging agents for non-invasive in vivo PET imaging. Therefore, the aim of this work is to develop class- and/or isoform-selective radiolabeled substrates of HDACs, with particular emphasis on class III (sirtuins, SIRTs). </p> <p>Herein, HDAC class IIa, SIRT1 and SIRT2-selective radiotracers have been developed and validated through in vitro and in vivo characterization. Two of these tracers, 18F-TFAHA for HDAC class IIa and and 2-[18F]PhAHA for SIRT1, have also been validated in a disease model demonstrating their utility in understanding epigenetic regulation in an aggressive form of brain cancer. The development of these targeted imaging agents may help develop new therapies for disease as well as methodologies for monitoring treatment effectiveness and disease progression.</p>","abstract_has_math":false,"creators":["Bonomi, Robin Edwards"],"institution":null,"degree_name":"Ph.D.","degree_level":"Open Access Dissertation","degree_discipline":"Biomedical Engineering","degree_department":null,"school":null,"contributors":["Juri G. Gelovani"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2016,"date_issued":"2016-01-01T08:00:00Z","date_published":"2016-01-01T08:00:00Z","updated_at":"2026-07-24T06:00:26Z","subjects":["Epigenetic Regulation","Epigenetics","HDAC","Molecular Imaging","PET Imaging","Sirtuins","Biomedical Engineering and Bioengineering"],"languages":[],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://digitalcommons.wayne.edu/oa_dissertations/1519","outbound_label":"Repository record","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Juri G. Gelovani"]},{"key":"dc:creator","label":"Author","values":["Bonomi, Robin Edwards"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.available","label":"Dc Date Available","values":["2017-12-07T08:00:00Z"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Biomedical Engineering"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Open Access Dissertation"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Ph.D."]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Epigenetic Regulation","Epigenetics","HDAC","Molecular Imaging","PET Imaging","Sirtuins","Biomedical Engineering and Bioengineering"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["https://digitalcommons.wayne.edu/oa_dissertations/1519"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["Over the past two decades, epigenetic regulation has become a rapidly growing, highly innovative and influential field of biology and medicine. Protein acetylation and deacetylation, two key epigenetic regulatory mechanisms, are mediated by histone acetylase transferases (HATs) and histone deacetylases (HDACs), respectively. To date, the vast majority of studies on epigenetic regulation have been conducted in cell cultures and tissue samples using conventional methodologies of molecular and cellular biology, which contain inherent limitations for monitoring therapy and disease. Therefore, there is a growing need for novel, advanced methodologies that allow for non-invasive detection and monitoring of HDAC–mediated epigenetic regulatory processes in different organs and tissues. One such methodology is molecular imaging with positron emission tomography (PET), which allows for non-invasive visualization and quantification of spatial and temporal dynamics of expression-activity of various receptors and enzymes in different organs and tissues in norm and disease. The availability of selective substrates to various classes and isoforms of HDACs would enable the development of radiolabeled imaging agents for non-invasive in vivo PET imaging. Therefore, the aim of this work is to develop class- and/or isoform-selective radiolabeled substrates of HDACs, with particular emphasis on class III (sirtuins, SIRTs).
Herein, HDAC class IIa, SIRT1 and SIRT2-selective radiotracers have been developed and validated through in vitro and in vivo characterization. Two of these tracers, 18F-TFAHA for HDAC class IIa and and 2-[18F]PhAHA for SIRT1, have also been validated in a disease model demonstrating their utility in understanding epigenetic regulation in an aggressive form of brain cancer. The development of these targeted imaging agents may help develop new therapies for disease as well as methodologies for monitoring treatment effectiveness and disease progression.
"]},{"key":"dc:title","label":"Title","values":["Development Of Novel Radiotracers For Pet Imaging Of Hdac-Mediated Epigenetic Regulation"]}]}],"canonical_facts":{"dc:contributor":["Juri G. Gelovani"],"dc:creator":["Bonomi, Robin Edwards"],"dc:date.available":["2017-12-07T08:00:00Z"],"dc:description.abstract":["Over the past two decades, epigenetic regulation has become a rapidly growing, highly innovative and influential field of biology and medicine. Protein acetylation and deacetylation, two key epigenetic regulatory mechanisms, are mediated by histone acetylase transferases (HATs) and histone deacetylases (HDACs), respectively. To date, the vast majority of studies on epigenetic regulation have been conducted in cell cultures and tissue samples using conventional methodologies of molecular and cellular biology, which contain inherent limitations for monitoring therapy and disease. Therefore, there is a growing need for novel, advanced methodologies that allow for non-invasive detection and monitoring of HDAC–mediated epigenetic regulatory processes in different organs and tissues. One such methodology is molecular imaging with positron emission tomography (PET), which allows for non-invasive visualization and quantification of spatial and temporal dynamics of expression-activity of various receptors and enzymes in different organs and tissues in norm and disease. The availability of selective substrates to various classes and isoforms of HDACs would enable the development of radiolabeled imaging agents for non-invasive in vivo PET imaging. Therefore, the aim of this work is to develop class- and/or isoform-selective radiolabeled substrates of HDACs, with particular emphasis on class III (sirtuins, SIRTs).
Herein, HDAC class IIa, SIRT1 and SIRT2-selective radiotracers have been developed and validated through in vitro and in vivo characterization. Two of these tracers, 18F-TFAHA for HDAC class IIa and and 2-[18F]PhAHA for SIRT1, have also been validated in a disease model demonstrating their utility in understanding epigenetic regulation in an aggressive form of brain cancer. The development of these targeted imaging agents may help develop new therapies for disease as well as methodologies for monitoring treatment effectiveness and disease progression.
"],"dc:identifier":["https://digitalcommons.wayne.edu/oa_dissertations/1519"],"dc:subject":["Epigenetic Regulation","Epigenetics","HDAC","Molecular Imaging","PET Imaging","Sirtuins","Biomedical Engineering and Bioengineering"],"dc:title":["Development Of Novel Radiotracers For Pet Imaging Of Hdac-Mediated Epigenetic Regulation"],"thesis:degree_discipline":["Biomedical Engineering"],"thesis:degree_level":["Open Access Dissertation"],"thesis:degree_name":["Ph.D."]},"updated_at":"2026-07-24T06:00:26Z"}