# Near-infrared Choline Kinase Sensors for Intraoperative Identification of Lung Tumor Margins

> **NIH NIH R01** · UNIVERSITY OF PENNSYLVANIA · 2021 · $359,645

## Abstract

PROJECT SUMMARY
The most important prognostic indicator following cancer surgery is complete resection. Intraoperative
detection of tumor margins is challenging, and residual disease continues to be the most common cause of
local recurrence. Complete resection results in prolonged patient survival and improved post-surgical quality of
life. Visual enhancement of tumors using near-infrared (NIR) imaging with targeted fluorophores can identify
lesions that are not detectable by visual observation or palpation. NIR imaging offers high resolution and
sensitivity and can be performed in real time in an intraoperative setting.
This application aims to test the efficacy of targeted NIR fluorophores for tumor detection in murine models of
lung cancer and to translate these findings to guide intraoperative surgical tumor removal in canine patients
with spontaneous lung cancer. Lung cancer is the leading cancer-related cause of death and the third most
diagnosed cancer in the United States. In non-small cell lung carcinomas (NSCLC), which represent 90% of
clinical lung cancers, tumor resection continues to be the most effective approach to cure patients with local
disease. Surgeons typically use visual inspection and finger palpation to define solid tumor margins.
However, this approach is often insufficient for the detection of residual disease, thus leading to locoregional
recurrence in up to 40% of patients and significantly reduced 5-year survival in this cohort.
In this proposal, we will use NIR probes synthesized in our laboratory and designed to detect choline kinase
(ChoK), a lipid kinase upregulated early in tumorigenesis and overexpressed in 56% of lung cancers and up to
83% of NSCLC. These probes will be tested for their ability to detect tumor margins in two models of NSCLC in
mice. We will evaluate time to tumor recurrence and survival in mice after fluorophore-targeted and non-
targeted surgical excision. From these data, one fluorophore will be selected for synthesis under GLP
conditions and its systemic toxicity evaluated in a cohort of canines. We will then recruit a patient cohort of 30
companion animals presenting to the University of Pennsylvania Veterinary School with spontaneous NSCLC.
Our Preliminary Studies indicate that canine NSCLC significantly overexpress ChoK and that this expression is
homogeneous throughout the tumor. We will employ intraoperative NIR fluorescence-guided surgery using our
ChoK probes for detection of tumors and identification of tumor margins. After resection and recovery, canine
patients will be monitored over time for tumor recurrence and patient survival. These data will be compared to
positive and negative control cohorts where tumors were resected using the non-targeted fluorophore
indocyanine green (ICG) or resected without the aid of NIR fluorescence guidance. These studies will test the
ability of our ChoK sensors to detect tumor margins in spontaneously occurring lung cancers in a canine
patient coho...

## Key facts

- **NIH application ID:** 10151567
- **Project number:** 5R01CA226412-04
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** EDWARD J DELIKATNY
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $359,645
- **Award type:** 5
- **Project period:** 2018-05-01 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10151567

## Citation

> US National Institutes of Health, RePORTER application 10151567, Near-infrared Choline Kinase Sensors for Intraoperative Identification of Lung Tumor Margins (5R01CA226412-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10151567. Licensed CC0.

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