# Development and validation of an intraoperative imaging agent for the peripheral nervous system

> **NIH NIH R01** · SLOAN-KETTERING INST CAN RESEARCH · 2021 · $508,361

## Abstract

Project Summary/Abstract
Twenty million Americans suffer from peripheral nerve injury caused by trauma and medical disorders, resulting
in a broad spectrum of potentially debilitating side effects. In one out of four cases, patients identify surgery as
the root cause of their nerve injury. Particularly during tumor resections or after traumatic injuries, tissue distortion
and poor visibility can challenge a surgeon's ability to precisely locate and preserve peripheral nerves. Intuitively,
surgical outcomes would improve tremendously if nerves could be highlighted using an exogeneous contrast
agent. In clinical practice, however, the current standard of care – visual examination and palpation – remains
unchanged.
The inability of surgeons to identify nerves during surgery represents an immense unmet clinical need, which we
propose to address within this application. We will develop and validate a translational fluorescent imaging agent
for the peripheral nervous system. In preparation for a clinical trial, we will show in mice and large animals that
the agent is safe for use in humans. Specifically, this proposal centers on Hsp1a, a peptide which we isolated
from the venom of a Peruvian tarantula, Homoeomma Spec. Peru, and which we found to be highly specific for
human Nav1.7. It has been shown that Nav1.7 is highly expressed in human peripheral nerve tissue. We believe
that a fluorescent Hsp1a will have tremendous value as an injectable, intraoperative guide during surgery, and
that the agent will provide surgeons with additional contrast, reducing iatrogenic injury and therefore surgical
morbidity.
To achieve this goal, we have assembled three specific aims (SAs), each of which will explore a distinct goal
toward showing that fluorescent Nav1.7 tracers can be translated to the clinic. In SA1, and supported by our
proof-of-principle data, we will synthesize a library of fluorescently labeled Hsp1a derivatives (n = 20), featuring
different fluorophores, attachment points and linker lengths. For all derivatives, we will determine the IC50 values
against Nav1.7 using patch-clamp electrophysiology; in SA2, pharmacokinetics and in vivo performance will be
determined using Nav1.7 expressing, tumor-bearing athymic nude mice and Nav1.7 deficient Scn9atm1Dgen/J mice.
For the most promising tracers (n = 3, based on IC50 and signal/noise ratios), we will test the minimum detectable
dose in cohorts of pigs. In SA3, we will interrogate the pharmacodynamic properties of the most promising Hsp1a
peptides. We will determine the maximum tolerated doses in mice while monitoring cardiovascular and
respiratory function. For the lead candidate, we will perform a 2-species GLP toxicity study (mice and dogs). If
successful, the current research proposal and generated data will form the foundation of a clinical phase I trial
with Hsp1a in oral cancer.

## Key facts

- **NIH application ID:** 10180965
- **Project number:** 5R01EB029769-02
- **Recipient organization:** SLOAN-KETTERING INST CAN RESEARCH
- **Principal Investigator:** Nagavarakishore Pillarsetty
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $508,361
- **Award type:** 5
- **Project period:** 2020-06-15 → 2024-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10180965

## Citation

> US National Institutes of Health, RePORTER application 10180965, Development and validation of an intraoperative imaging agent for the peripheral nervous system (5R01EB029769-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10180965. Licensed CC0.

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