# Project 4: New Approaches to Improving the Effectiveness of Radionuclide Targeted Treatments in Neuroendocrine Tumors

> **NIH NIH P50** · UNIVERSITY OF IOWA · 2020 · $228,031

## Abstract

Neuroendocrine tumors (NETs) are considered an Orphan Disease with a low incidence (<10000/yr) in the 
United States. Consequently, it has proven very difficult to secure the interest or resources needed to bring 
newer treatments to the clinical arena for these patients. Although slow to progress in the early stages, once 
NETs metastasize, the current 5-year survival rate is <30%. Newer, more effective forms of therapy are 
urgently needed. Targeted radionuclide therapies using single agents such as 131I-metaiodobenzylguanidine 
(131I MIBG) and 90Y-DOTA-tyr3-Octreotide (90Y-DOTATOC) have shown promise for therapy of small bowel 
NETs with response rates of 20-40%. Unfortunately, complete responses are notably uncommon, occurring in 
less than 10% of patients and response duration is often disappointing as well. We propose a Phase I clinical 
trial combining 90Y-DOTATOC and 131I MIBG that should provide an increase in the radiation dose delivered to 
tumors without exceeding safe limits for normal kidney and bone marrow. This trial design, based on strong 
preliminary imaging data and radiation dose modeling, has the potential to provide durable therapeutic benefit 
for patients with small bowel NETs where other therapeutic strategies fall short. In further basic science 
studies, we propose an innovative strategy targeting unique G-protein coupled receptor hetero-dimers such as 
somatostatin receptor/dopamine receptor conjugates that are expressed in NETs. Preliminary data 
demonstrate that these new targeting agents have high affinity binding to tumor cells; they are predicted to be 
highly specific for tumor cells as the hetero-dimeric receptors are rarely expressed in normal tissues. 
Successful development of these unique radionuclide therapies will provide a new paradigm for molecular 
targeting and image-guided radionuclide therapy that will likely be translated to other malignancies.

## Key facts

- **NIH application ID:** 10264531
- **Project number:** 3P50CA174521-05S2
- **Recipient organization:** UNIVERSITY OF IOWA
- **Principal Investigator:** DAVID L BUSHNELL
- **Activity code:** P50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $228,031
- **Award type:** 3
- **Project period:** 2015-09-01 → 2021-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10264531

## Citation

> US National Institutes of Health, RePORTER application 10264531, Project 4: New Approaches to Improving the Effectiveness of Radionuclide Targeted Treatments in Neuroendocrine Tumors (3P50CA174521-05S2). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10264531. Licensed CC0.

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