# The development of novel PET/NIRF agents for hyperparathyroidism management

> **NIH NIH R01** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2024 · $474,920

## Abstract

Abstract
 Affecting >100,000 persons each year in the United States, primary hyperparathyroidism (PHPT) is a
common disorder that leads to significant morbidity. For PHPT patients, surgically removing the affected
parathyroid gland is the only curative option. The current state of the art is to use preoperative imaging to locate
abnormal parathyroid glands, aiming to perform a focused surgical approach that can limit unnecessary
dissection. In addition, localization can reveal abnormal locations of the parathyroid glands outside the neck
which can prevent fruitless neck exploration and guide alternative surgical approaches. Despite the progress,
current imaging techniques have several limitations on detecting small glands (especially in unusual locations)
and multiple abnormal parathyroids (occurs in 15-20% of cases). This application proposes to develop new
imaging agents that can efficiently detect parathyroid glands preoperatively, and be used intraoperatively to
guide exploration. In detail, we will construct innovative positron emission tomography (PET) agents targeting
markers specific for parathyroid glands, and PET/near-infrared fluorescence (NIRF) dual modality agents that
seamlessly integrate parathyroid detection and image-guided surgery. This project is built upon our recent
advances on radiofluorination, PET probe development and dual modality imaging. In detail, calcium sensing
receptor (CSR) is a Class C G-protein coupled receptor that is highly expressed in the parathyroid gland and the
kidneys. The development of CSR-specific pharmaceuticals for imaging could potentially lead to novel PET
agents that are highly specific for parathyroid (kidneys are located far away from our area of interest, which will
not interfere with PHPT detection). The use of a dual tracer (optical and PET) would not only introduce high
sensitivity for parathyroid detection, but also facilitate subsequent gland localization during surgery. There are
three aims for this project. Aim 1 will develop PET agents for parathyroid imaging based on novel ligands of CSR.
Aim 2 will develop a robust radiofluorination method to generate 18F labeled NIRF dyes that could localize at
parathyroid gland selectively. Aim 3 will evaluate our lead agents in rodent model bearing transplanted human
hyperparathyroidism tissue. The lead agent will be further characterized in nonhuman primates.
 In our preliminary study, we have successfully introduced 18F (radio tag) into cinacalcet (a small molecule
targeting CSR) using photoredox radiofluorination. The resulting agent could be preferentially taken up by
parathyroid gland in rats. Initial study in non-human primate also suggested the great potential of using 18F-
cinacalcet for parathyroid imaging. In aim 2, we successfully generated 18F labeled NIRF dyes for specific
parathyroid and thyroid gland targeting. This approach would address the clinical need by integrating PET with
image-guided surgery. In summary, the overarching goa...

## Key facts

- **NIH application ID:** 10911916
- **Project number:** 5R01DK128447-04
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** LAWRENCE Thomas KIM
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $474,920
- **Award type:** 5
- **Project period:** 2021-09-20 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10911916

## Citation

> US National Institutes of Health, RePORTER application 10911916, The development of novel PET/NIRF agents for hyperparathyroidism management (5R01DK128447-04). Retrieved via AI Analytics 2026-06-10 from https://api.ai-analytics.org/grant/nih/10911916. Licensed CC0.

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