All ETDs from UAB

Advisory Committee Chair

Herbert Chen

Advisory Committee Members

Renata Jaskula-Sztul

Anna Sorace

Jack Rogers

Laura Lambert

Document Type

Dissertation

Date of Award

2021

Degree Name by School

Doctor of Philosophy (PhD) Heersink School of Medicine

Abstract

Neuroendocrine cancer is complex disease of the diffuse neuroendocrine system. Neuroendocrine tumors (NETs) can arise throughout the body, including the lungs and pancreas. These tumors are phenotypically and genetically heterogeneous, making accurate diagnoses difficult with current imaging standards. New diagnostic options, coupled with a better understanding of neuroendocrine cancer etiology, is urgent and necessary to provide patients with better futures. Many NETs overexpress somatostatin receptor 2 (SSTR2) on their cellular surfaces, making patients eligible for [68Ga]-DOTATATE PET/CT imaging and SSTR2-based therapies. However, patients that lack sufficient SSTR2 overexpression cannot benefit from SSTR2-targeted imaging or therapeutic options. We found that histone deacetylase inhibitors (HDAC) inhibitors can upregulate the functional expression of SSTR2. We have demonstrated the upregulation of SSTR2 expression in pulmonary and pancreatic NETs using five different HDAC inhibitors. Changes in expression were evaluated transcriptionally and translationally through in vitro and in vivo techniques. The functional increase of SSTR2 in NETs after HDAC inhibitor treatment was confirmed by small animal [68Ga]-DOTATATE PET/CT imaging. Our findings describe a potential method of increasing the membranous density of SSTR2 in pulmonary and pancreatic NETs. Enhanced SSTR2 incidence on the surface on NET cells could enhance the efficacy of SSTR2-based imaging and therapeutics.

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