Friday, October 3, 2025 10/3/2025

Receptor-Targeted Fluorescence-Guided Surgery in Pancreatic Neuroendocrine Tumors

Award Number: R01CA263512
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 07/01/2022
PERIOD OF PERFORMANCE END DATE: 02/28/2028

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Receptor-Targeted Fluorescence-Guided Surgery in Pancreatic Neuroendocrine Tumors - 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 preoperative nuclear imaging, FGS, and histopathology. We also showed preliminary evidence of safety in mice and identified a manufacturing process to support agent scale-up. We seek to build on these findings and propose the following specific aims: (1) implement a manufacturing plan to support IND-enabling studies, (2) examine preclinical toxicity/pharmacology and complete the required documentation for submission of an IND application, and (3) conduct a first-in-human phase 1 clinical study in patients with pNETs. To accomplish our aims, we have formed a strong investigational team that combines the expertise of Dr. Azhdarinia (contact Pl) in contrast agent development with the expertise of Dr. lkoma (multi-Pl) in surgical oncology. The team is supported by surgeons from MD Anderson Cancer Center that specialize in treating NETs and medical oncologists who oversee one of the world's highest-volume NET centers. Successful completion of our aims will demonstrate feasibility for phase 2/3 studies to evaluate the efficacy of our strategy and will broadly impact the field by serving as a model for the development of other targeted agents that are suitable for surgical guidance.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2025 ( Subtotal = $485,072 )
2025	2025	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT HOUSTON	7000 FANNIN ST FL 9	HOUSTON	TX	77030	HARRIS	USA	Cancer Detection and Diagnosis Research	000	3	2/19/2025	NON-COMPETING CONTINUATION	$436,565
2025	2025	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT HOUSTON	7000 FANNIN ST FL 9	HOUSTON	TX	77030	HARRIS	USA	Cancer Detection and Diagnosis Research	001	3	9/8/2025	NON-COMPETING CONTINUATION	$48,507
														Subtotal = $485,072

Issue Date FY: 2024 ( Subtotal = $0 )
2024	2023	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT HOUSTON	7000 FANNIN ST FL 9	HOUSTON	TX	77030	HARRIS	USA	Cancer Detection and Diagnosis Research	000	2	7/11/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $628,150 )
2023	2023	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT HOUSTON, THE	7000 FANNIN ST	HOUSTON	TX	77030	HARRIS	USA	Cancer Detection and Diagnosis Research	000	2	8/17/2023	NON-COMPETING CONTINUATION	$628,150
														Subtotal = $628,150

Issue Date FY: 2022 ( Subtotal = $662,090 )
2022	2022	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT HOUSTON, THE	7000 FANNIN ST	HOUSTON	TX	77030	HARRIS	USA	Cancer Detection and Diagnosis Research	000	1	6/28/2022	NEW	$662,090
														Subtotal = $662,090

Grand Total All Awards = $1,775,312

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Receptor-Targeted Fluorescence-Guided Surgery in Pancreatic Neuroendocrine Tumors

Award Number: R01CA263512

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 07/01/2022

PERIOD OF PERFORMANCE END DATE: 02/28/2028

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