# Project 1: Theranostics in Neuroendocrine Tumors

> **NIH NIH P50** · UNIVERSITY OF IOWA · 2021 · $96,189

## Abstract

Neuroendocrine tumors (NETs) constitute an unrecognized health threat to children and adults. The incidence 
and prevalence of NETs is rising in the United States; yet, there is very little research on NETs, and no 
effective treatment for patients with metastatic disease, over half of whom die within five years of diagnosis 
according to latest SEER data. These tumors do not respond to conventional chemotherapy or external beam 
radiation, making development of new diagnostic and therapeutic options imperative. We hypothesize that 
theranostics, use of a single compound as both a therapeutic and a diagnostic agent, will meet this critical 
need for children and adults with NETs. The translational component of this proposal will identify new 
theranostic targets, design and synthesize new targeting agents, and test their efficacy in vivo. Lead 
compounds that meet strict criteria as high affinity PET tracers and molecularly targeted therapeutic agents in 
pre-clinical models of bronchial, small bowel, or pancreatic neuroendocrine tumors will be brought forward to 
 first in human PET imaging trials through an Exploratory IND mechanisms. Specific aims are: 
1. Design and synthesize unique, high-affinity, stable ligands for use in GPCR targeted theranostics. 
Expression data from Project 3 has identified three GPCR (OXTR, VPAC1, MC1R) as new targets in NETs. 
Theranostic radiopharmaceuticals will be designed and synthesized using NMR and 3-D modeling to guide 
chemical modifications that enhance affinity, specificity and stability of candidate ligands. Peptide libraries 
incorporating D- and unnatural amino acids, cyclization strategies, and lysine substitutions for DOTA 
conjugation will be synthesized; binding affinity, specificity and stability will be determined in vitro. 
2. Characterize in vivo specificity, stability, pharmacokinetics, and cytotoxicity of new GPCR targeted 
theranostic compounds in mouse models of neuroendocrine tumors. We will conduct theranostic pre- 
clinical in vitro and in vivo testing of lead GPCR targeted ligands in mouse models of NETs with the goal of 
having at least two analogs ready to test as PET tracers in humans by year 5. 
3. Examine safety and efficacy of new GPCR targeted PET tracers in humans using exploratory IND. 
Agents that pass rigorous pre-clinical testing will then be synthesized under GMP conditions. An exploratory 
IND will be obtained to examine the ability of lead candidates to localize to neuroendocrine tumors in first in 
human trials. Successful tracers that meet the strict theranostic criteria and demonstrate safety, specificity, 
and reproducibility as a PET tracer in patients with NETs, will be further developed through a full IND. 
Successful completion of these pre-clinical theranostic trials and first in human molecularly targeted PET 
imaging trials will pave the way for development of new radiotherapeutics with the ultimate goal of providing 
dual-target, dual-radionuclide therapy for ...

## Key facts

- **NIH application ID:** 10487602
- **Project number:** 3P50CA174521-05S3
- **Recipient organization:** UNIVERSITY OF IOWA
- **Principal Investigator:** Yusuf Menda
- **Activity code:** P50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $96,189
- **Award type:** 3
- **Project period:** 2015-09-01 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10487602

## Citation

> US National Institutes of Health, RePORTER application 10487602, Project 1: Theranostics in Neuroendocrine Tumors (3P50CA174521-05S3). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10487602. Licensed CC0.

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