# Imaging of alterations in SSTR2 expression with histone deacetylase (HDAC) inhibitors treatment for neuroendocrine tumors

> **NIH NIH R21** · UNIVERSITY OF ALABAMA AT BIRMINGHAM · 2020 · $381,830

## Abstract

ABSTRACT
Neuroendocrine tumors (NETs) are hormone secreting neoplasms, including carcinoids, islet cell tumors, and
medullary thyroid cancers. Management of NETs has been problematic since the disease is often diagnosed at
metastatic stage when therapeutic options are limited. While, Positron Emission Tomography (PET)/CT based
on the radiolabeled sugar analogue [18F]FDG is used to diagnose and stage NETs, it is often suboptimal due to
low metabolic activity in these tumors. More recently, a newly approved technique for NET imaging,
[68Ga]DOTATATE PET/CT, that specifically targets somatostatin receptor subtype 2 (SSTR2) is becoming more
standard, as many NETs overexpress SSTR2. This imaging technique plays an important role in patient care as
the outcomes are used to stratify patients for SSTR2 targeted treatment. However, NET patients with
diminished SSTR2 expression as determined by imaging are not eligible for any type of SSTR2-specific
treatment. Herein, we propose a method to enhance and enable targeted therapies for these patients. We have
found that the epigenetic modifiers such as histone deacetylase (HDAC) inhibitors: thailandepsin A (TDP-A) and
valproic acid (VPA) can upregulate the expression of SSTR2 in NETs. Our approach will likely result in a new
targeted treatment strategy for NET patients who have very limited therapeutic options. The specific
objective of this application is to rigorously characterize the HDAC inhibitors enhanced SSTR2 expression in
NET cell lines and xenografts. We propose to assess these changes using gold standard biological methods and
will then develop strategies to validate this upregulation in vivo in a longitudinal, non-invasive manner using
existing state-of-the-art clinically translatable imaging techniques. Our central hypothesis is that these HDAC
inhibitors can upregulate SSTR2 which can be assessed by advanced imaging techniques thus making patients
eligible for subsequent SSTR2 targeted therapy with the radiotherapeutic [177Lu]DOTATATE. To test this
hypothesis, we propose to fully evaluate this targeted therapy in two Specific Aims. First, we will use a non-
cytotoxic dose of TDP-A and VPA to induce SSTR2 expression in NET cell lines and elucidate the receptor
density and functional activity. In this aim, we will also assess the SSTR2 basal expression in NET patients’
tissue microarray (TMA) blocks (Aim1). Next, we will test the in vivo [68Ga]DOTATATE uptake and biodistribution
as a result of target upregulation using NET xenografts. We will conduct a highly translational method of imaging
of SSTR2 expression alterations in NET xenografts before and after treatment using [68Ga]DOTATATE small
animal PET/CT (Aim2). Our long-term goal is to translate this novel strategy to achieve improved imaging and
potential curative therapy through the specific targeting of enhanced SSTR2 expression.

## Key facts

- **NIH application ID:** 10044579
- **Project number:** 1R21CA245580-01A1
- **Recipient organization:** UNIVERSITY OF ALABAMA AT BIRMINGHAM
- **Principal Investigator:** Renata Jaskula-Sztul
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $381,830
- **Award type:** 1
- **Project period:** 2020-07-07 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10044579

## Citation

> US National Institutes of Health, RePORTER application 10044579, Imaging of alterations in SSTR2 expression with histone deacetylase (HDAC) inhibitors treatment for neuroendocrine tumors (1R21CA245580-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10044579. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*