# Novel Receptor-Targeting Peptides for Melanoma Therapy

> **NIH NIH R01** · UNIVERSITY OF COLORADO DENVER · 2020 · $390,754

## Abstract

Malignant melanoma is the most lethal form of skin cancer with an increasing incidence in the United
States. Unfortunately, no curative treatment exists for metastatic melanoma. Despite the significant advance of
molecularly targeted approaches in treating metastatic melanoma over the past years, the long-term survival
remains <10%. Thus, there is an urgent need to develop new treatment strategies for metastatic melanoma.
 Melanocortin-1 receptor (MC1R) is a distinct molecular target due to its over-expression on >80% of human
metastatic melanomas. We have developed a novel class of MC1R-targeting lactam-cyclized CycMSHhex
peptides for melanoma imaging. The remarkable first-in-man clinical results regarding the visualization of
melanoma metastases using our CycMSHhex peptide clearly demonstrate the clinical significance of MC1R in
melanoma imaging, as well as underscore the urgent need to develop MC1R-targeting therapeutic agents for
treating patients with metastatic melanoma. Thus, we propose to develop novel MC1R-targeting theranostic
(diagnostic & therapeutic) ²⁰³Pb/²¹²Pb-DOTA-Linker-Nle-CycMSHhex peptides for imaging-guided therapy of
melanoma in this project. We hypothesize that DOTA-Linker-Nle-CycMSHhex peptides can specifically bind to
MC1Rs and target matched-pair theranostic ²⁰³Pb/²¹²Pb to human melanoma cells for imaging-guided therapy.
We will use hydrocarbon and polyethylene glycol (PEG) linkers to improve melanoma uptake and clearance
properties of ²⁰³Pb/²¹²Pb-DOTA-Linker-Nle-CycMSHhex, and then examine the therapeutic efficacies of selected
²¹²Pb-DOTA-Linker-Nle-CycMSHhex peptides in human melanoma xenografts and metastases in this project.
We have been awarded 4 US patents for our novel CycMSHhex peptides, demonstrating the originality and
novelty of this project.
 The objective of this project is to develop novel MC1R-targeting theranostic ²⁰³Pb/²¹²Pb-DOTA-Linker-Nle-
CycMSHhex peptides to treat metastatic melanoma via imaging-guided therapy. Our positive preliminary results
strongly support our hypothesis and research design. Importantly, we have assembled a strong research team
with established expertise that is uniquely suited to carry out this exciting translational project. The success of
this project will provide a novel imaging tool (²⁰³Pb-peptide) to identify MC1R-positive patients who will benefit
from ²¹²Pb-peptide treatments, to determine safe and efficacious doses, and to monitor patients' responses to
treatments. Moreover, the success of this project will open the avenue of treating metastatic melanoma with
the combination of receptor-targeted alpha therapy (²¹²Pb-peptide) and other treatments in the future, providing
patients with personalized diagnoses and treatments. Identification of novel theranostic peptides in this project
will pave the way for evaluating this novel class of peptide radiopharmaceuticals in US FDA-approved clinical
trials in the future, and enhance the opportunities of cures to patients with met...

## Key facts

- **NIH application ID:** 9899954
- **Project number:** 5R01CA225837-03
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** Yubin Miao
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $390,754
- **Award type:** 5
- **Project period:** 2018-04-01 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9899954

## Citation

> US National Institutes of Health, RePORTER application 9899954, Novel Receptor-Targeting Peptides for Melanoma Therapy (5R01CA225837-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9899954. Licensed CC0.

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