# Receptor-Targeted Fluorescence-Guided Surgery in Pancreatic Neuroendocrine Tumors

> **NIH CA R01** · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · 2026 · $482,257

## Abstract

PROJECT SUMMARY
The goal of this proposal is to clinically translate a fluorescently labeled contrast agent that improves surgical
outcomes in patients with pancreatic neuroendocrine tumors (pNETs). Surgery is the main treatment option for
these patients and can be curative if tumors are completely removed. However, the inability to accurately identify
pNETs intraoperatively can lead to sub-optimal surgical outcomes and decreased survival. Fluorescence-guided
surgery (FGS) could potentially address this clinical need, but the absence of a molecularly targeted fluorescent
agent has thus far limited its utility in pNETs. Accordingly, our team converted the clinical radiotracer, 66GaDOTA-
TOC, into a fluorescent counterpart that showed highly selective uptake in xenograft models and surgical
biospecimens that express somatostatin receptor subtype 2 (SSTR2). A key drawback of the dye moiety, known
as IR800, is its highly negative charge that leads to non-specific interaction with serum proteins and tissues. As
a result, agent uptake is significant in non-target tissues and leads to reduced image contrast. Zwitterionic (i.e.,
charge-balanced) dyes have been developed to overcome this limitation and have outperformed IR800
counterparts in comparative studies. To evaluate the effects of dye charge on in vivo performance, we replaced
IR800 with the charge-balanced near-infrared fluorescent dye, FNIR-Tag, to produce the second-generation
agent, MMC(FNIR-Tag)-TOC. Our preliminary data showed that MMC(FNIR-Tag)-TOC had significantly lower
background signal than the first-generation agent in nearly all normal tissues along with higher tumor uptake.
The remarkable increase in tumor-to-background ratios suggests excellent potential for intraoperative detection
of SSTR2-expressing tumors and high translational utility as demonstrated in an SSTR2-expressing patient-derived
xenograft (PDX) tumor model and in an orthotopic tumor model that showed excellent correlation
between preoper

## Key facts

- **NIH application ID:** 11289293
- **Project number:** 5R01CA263512-04
- **Recipient organization:** UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
- **Principal Investigator:** Ali  Azhdarinia; Naruhiko  Ikoma
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** CA
- **Fiscal year:** 2026
- **Award amount:** $482,257
- **Award type:** 5
- **Project period:** 2022-07-01T00:00:00 → 2028-02-28T00:00:00

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11289293

## Citation

> US National Institutes of Health, RePORTER application 11289293, Receptor-Targeted Fluorescence-Guided Surgery in Pancreatic Neuroendocrine Tumors (5R01CA263512-04). Retrieved via AI Analytics 2026-05-19 from https://api.ai-analytics.org/grant/nih/11289293. Licensed CC0.

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