# A novel molecularly targeted theranostic approach via the alphavbeta6 integrin for the detection and treatment of metastatic cancers

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA AT DAVIS · 2023 · $664,690

## Abstract

PROJECT SUMMARY/ABSTRACT
We propose to evaluate a novel αvβ6 integrin molecularly targeted theranostic approach for the detection and
treatment of metastatic cancers. The αvβ6 integrin is a cell surface receptor that is low or undetectable in normal
adult epithelium but is widely expressed on numerous carcinomas. There is a statistically significant association
between the high expression of the αvβ6 integrin, distant spread, and poor survival. We previously developed
an αvβ6 -Binding Peptide (BP) with nanomolar affinity and high selectivity for the integrin αvβ66. Our prior clinical
data demonstrates that using [18F]-αvβ6 -BP PET/CT imaging we can detect both primary tumors and
metastases. PET images showed low background uptake in normal brain, lungs, liver, and osseous skeleton
which are common sites of metastatic disease. Furthermore, sub-centimeter metastases to these organs were
detected using [18F]αvβ6 -BP PET/CT. We further developed our αvβ6-BP into a novel theranostic pair, [68Ga]Ga
DOTA-5G and [177Lu]Lu DOTA-ABM-5G in which [68Ga]Ga DOTA-5G is being developed as a diagnostic and
[177Lu]Lu DOTA-ABM-5G is being developed as a radiotherapy. We now propose a prospective clinical trial to
test the [68Ga]Ga DOTA-5G and [177Lu]Lu DOTA-ABM-5G in patients with metastatic disease. Patients will
undergo [68Ga]Ga DOTA-5G PET/CT scans to confirm eligibility for the [177Lu]Lu DOTA-ABM-5G therapy and
follow up [68Ga]Ga DOTA-5G PET/CT scans to evaluate treatment response. We hypothesize that a) [68Ga]Ga
DOTA-5G will detect lesions in patients with metastatic cancers b) the theranostic pair [68Ga]Ga DOTA-5G/
[177Lu]Lu DOTA-ABM-5G will be safe and well tolerated; and c) a therapeutic response will be achieved with a
single dose of [177Lu]Lu DOTA-ABM-5G. This proposal leverages the complimentary expertise of Dr. Sutcliffe to
develop and translate the theranostic agents, and Dr. Foster to treat patients and interpret images for treatment
response. The ability of the Sutcliffe lab to generate the theranostic agents in this study for patients treated at
UC Davis maximizes existing resources and a well-established successful collaboration between the PIs,
increasing the speed of translation of these theranostic agents from research to Phase II trials and ultimately, a
standard of care option for patients with metastatic disease. Given the role of the αvβ6 integrin receptor in the
processes of invasion and metastasis, αvβ6 is a very attractive target for the detection and treatment of metastatic
cancers and could have broad impact across multiple cancers. [68Ga]Ga DOTA-5G will more accurately and
non-invasively detect disease and the promising pharmacokinetic profile of the theranostics proposed suggests
that off-target toxicity of this [177Lu]Lu DOTA-ABM-5G therapy is not expected. This poses a major improvement
over current treatments that are known to cause bone marrow toxicity, hepatobiliary toxicity, and cardiotoxicity.
Collectively, this proposal will s...

## Key facts

- **NIH application ID:** 10636199
- **Project number:** 1R01CA279342-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA AT DAVIS
- **Principal Investigator:** Cameron Carl Foster
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $664,690
- **Award type:** 1
- **Project period:** 2023-09-21 → 2028-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10636199

## Citation

> US National Institutes of Health, RePORTER application 10636199, A novel molecularly targeted theranostic approach via the alphavbeta6 integrin for the detection and treatment of metastatic cancers (1R01CA279342-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10636199. Licensed CC0.

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