[18F]-αvβ6-BP PET Imaging for Lung Cancer

Overseen By Principal Investigator

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: University of California, Davis

Disqualifiers: Pregnancy, Prisoners, Concurrent malignancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 2

20 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new imaging method to better understand and assess lung cancer, specifically for those with non-small cell lung cancer (NSCLC) that has spread to the brain. The study uses a special imaging agent called [18F]-αvβ6-BP (Fluorine-18-AlphaVBeta6-Binding Peptide) in a PET scan to determine if it can more accurately show the extent of the cancer. It may suit individuals diagnosed with NSCLC and brain metastases who have a life expectancy of at least three months and have undergone a PET scan and brain MRI within the past 21 days. Participants will receive the imaging agent through an IV and then undergo a PET/CT scan. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new imaging method.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What prior data suggests that [18F]-αvβ6-BP is safe as a PET imaging agent for NSCLC patients?

Research has shown that [18F]-αvβ6-BP, a new imaging agent for lung cancer, is being tested for safety in humans. Early results suggest manageable side effects. In initial tests, patients reported no major safety issues, indicating that the agent might be safe for detecting cancer spread. However, as this is an early-stage study, further research is needed to confirm these safety findings. ^{1 2 3 4 5}

Why are researchers excited about this trial?

[18F]-αvβ6-BP is unique because it offers a new way to visualize lung cancer using PET imaging. Unlike traditional imaging methods, this treatment targets the αvβ6 integrin, a protein often overexpressed in cancer cells, providing a more precise picture of the tumor's activity. Researchers are excited because this approach could lead to earlier and more accurate detection of lung cancer, potentially improving treatment decisions and outcomes.

What evidence suggests that [18F]-αvβ6-BP is effective for imaging non-small cell lung cancer?

Research has shown that [18F]-αvβ6-BP holds promise for imaging in patients with Non-Small Cell Lung Cancer (NSCLC). This imaging agent targets the protein αvβ6, commonly present in cancer cells but not in normal tissues. Studies have demonstrated that this compound enables clear and effective imaging of the primary cancer and its metastasis to areas such as the brain, bones, liver, and lungs. Early human imaging results indicated significant uptake in these regions, suggesting it could help doctors identify cancer spread. This makes [18F]-αvβ6-BP a potentially powerful tool for diagnosing and assessing the extent of NSCLC, including metastasis to the brain. Participants in this trial will receive [18F]-αvβ6-BP and undergo a PET/CT scan to evaluate its effectiveness in imaging NSCLC. ^{2 5 6 7 8}

Who Is on the Research Team?

Julie L. Sutcliffe, PhD

Principal Investigator

The Regents of the University of California (Davis)

Are You a Good Fit for This Trial?

This trial is for men and women over 18 with Non-Small Cell Lung Cancer (NSCLC) that has spread to the brain. They should be planning more cancer treatment, have a life expectancy of at least 3 months, and able to undergo PET/CT scans. Pregnant or breastfeeding individuals, prisoners, those with other cancers, or who exceed weight limits for scanning (>350lbs) cannot participate.

Inclusion Criteria

I am older than 18 years.

Your doctor believes you will live for at least three more months.

Ability to understand and willingness to sign a written informed consent document.

Exclusion Criteria

Pregnant or lactating women

Prisoners

I weigh more than 350lbs and cannot have a PET/CT scan.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Imaging

Participants undergo [18F]-αvβ6-BP PET/CT at baseline in addition to standard-of-care [18F]-FDG PET/CT body and MRI of the brain

1 day

1 visit (in-person)

Standard-of-Care Therapy

Participants undergo standard-of-care cancer directed therapy

8-12 weeks

Re-staging Imaging

Participants are re-staged with [18F]-αvβ6-BP PET/CT, [18F]-FDG PET/CT, and MRI 8-12 weeks after baseline imaging

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to six months

What Are the Treatments Tested in This Trial?

Interventions

• [18F]-αvβ6-BP

Trial Overview [18F]-αvβ6-BP is being tested as a new imaging agent in PET/CT scans for patients with NSCLC and brain metastases. The study aims to see if this agent can better assess the disease compared to current methods.

How Is the Trial Designed?

Group I: Experimental [18F]-αvβ6-BP Experimental Treatment 1 Intervention

Patients receive \[18F\]-αvβ6-BP BP IV and then undergo a PET/CT scan over 30 minutes 60 minutes post-injection.

Who Is Running the Clinical Trial?

University of California, Davis

Lead Sponsor

Trials

958

Recruited

4,816,000+

United States Department of Defense

Collaborator

Trials

940

Recruited

339,000+

Published Research Related to This Trial

The integrin αvβ6-binding peptide ([18F]αvβ6-BP) showed excellent selectivity and affinity for its target, allowing for effective noninvasive imaging of various cancers, including lung, colon, breast, and pancreatic cancers, in a first-in-human PET/CT study.

The imaging agent was well tolerated by patients with no significant side effects, and it demonstrated significant uptake in tumors and metastases, indicating its potential for broad clinical application in cancer diagnostics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preclinical Development and First-in-Human Imaging of the Integrin αvβ6 with [18F]αvβ6-Binding Peptide in Metastatic Carcinoma. Hausner, SH., Bold, RJ., Cheuy, LY., et al.[2023]

The peptide A20FMDV2 specifically binds to the integrin alphavbeta6, which is highly expressed in aggressive cancers, making it a promising target for both imaging and therapy.

In vivo studies showed that indium-111-labelled A20FMDV2 has at least seven times higher retention in alphavbeta6-positive tumors compared to negative ones, allowing for effective imaging and potential therapeutic delivery in these cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High-resolution in vivo imaging of breast cancer by targeting the pro-invasive integrin alphavbeta6. Saha, A., Ellison, D., Thomas, GJ., et al.[2022]

The radiolabeled peptide 18F-FB-A20FMDV2 was safely administered to four healthy subjects, showing no adverse effects or toxicological concerns, indicating its potential for clinical use in imaging αvβ6 integrin levels.

The imaging results demonstrated significant uptake in various organs, particularly the bladder, and the effective dose was low enough to allow for multiple scans, suggesting a promising safety profile for future applications in cancer and fibrosis assessment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Microdose PET Study of the Safety, Immunogenicity, Biodistribution, and Radiation Dosimetry of 18F-FB-A20FMDV2 for Imaging the Integrin αvβ6. Keat, N., Kenny, J., Chen, K., et al.[2022]

The novel peptide CP-7 was designed to specifically target VEGFR-3, which is overexpressed in lung cancer, showing strong binding and uptake in A549 lung cancer cells, indicating its potential for targeted drug delivery.

In vivo studies demonstrated that the 131I-labeled CP-7 peptide was stable in serum and showed high uptake in VEGFR-3 expressing tumors while exhibiting low accumulation in the heart, suggesting a favorable safety profile for potential therapeutic applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

De Novo Computational Design for Development of a Peptide Ligand Oriented to VEGFR-3 with High Affinity and Long Circulation. Li, HM., Dong, ZP., Wang, QY., et al.[2018]

The integrin alphavbeta6 is a promising target for noninvasive cancer imaging due to its low expression in normal tissues and high levels in aggressive tumors, making it useful for detecting cancer during wound healing and inflammation.

The peptide A20FMDV2, which selectively inhibits alphavbeta6 with high potency, was successfully used in PET imaging to differentiate between alphavbeta6-positive and negative tumors in mice, indicating its potential for early cancer detection and management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of a peptide derived from foot-and-mouth disease virus for the noninvasive imaging of human cancer: generation and evaluation of 4-[18F]fluorobenzoyl A20FMDV2 for in vivo imaging of integrin alphavbeta6 expression with positron emission tomography. Hausner, SH., DiCara, D., Marik, J., et al.[2022]

A new peptidic probe for PET imaging of non-small cell lung cancer (NSCLC) was developed, showing four-fold higher binding affinity and three-fold greater tumor uptake compared to a monovalent version, indicating the effectiveness of multivalent design.

The optimized probe, 64Cu-AcD10, significantly reduced kidney accumulation while maintaining tumor targeting, enhancing its safety profile for non-invasive imaging of αvβ6+ NSCLC tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dimerization of a phage-display selected peptide for imaging of αvβ6- integrin: two approaches to the multivalent effect. Singh, AN., McGuire, MJ., Li, S., et al.[2022]

The study evaluated 18F-dVIP as a potential imaging agent for breast cancer, but found that 2-deoxy-2-[18F]fluoro-D-glucose (FDG) had significantly better tumor accumulation and contrast, being two to three times more effective in targeting tumors.

While VIP receptors were present in the breast cancer tumors, their low concentration contributed to the lower uptake of 18F-dVIP, indicating that FDG remains the more effective imaging option for breast cancer detection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of an 18F labeled derivative of vasoactive intestinal peptide and 2-deoxy-2-[18F]fluoro-D-glucose in nude mice bearing breast cancer xenografts. Jagoda, EM., Aloj, L., Seidel, J., et al.[2019]

The αvβ6-BP peptide, when radiolabeled with aluminum [18F]fluoride, shows excellent selectivity for the integrin αvβ6, which is important for imaging certain cancers, with a strong binding affinity (IC50 of 3-7 nM).

Introducing an albumin binding moiety (ABM) significantly improved the pharmacokinetics of the radiotracer, leading to prolonged circulation in the bloodstream and higher uptake in αvβ6-positive tumors, making it a promising agent for PET imaging.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Effects of an Albumin Binding Moiety on the Targeting and Pharmacokinetics of an Integrin αvβ6-Selective Peptide Labeled with Aluminum [18F]Fluoride. Hausner, SH., Bauer, N., Davis, RA., et al.[2022]

The new imaging agent [(18)F]FBA-PEG(28)-A20FMDV2 shows significantly improved binding and tumor retention for the alpha(v)beta(6) receptor, which is often overexpressed in various cancers, including pancreatic cancer, compared to previous agents.

This imaging agent demonstrated superior performance over the standard imaging method [(18)F]FDG, achieving high tumor-to-background ratios, indicating its potential for better detection of pancreatic ductal adenocarcinoma and improving patient care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeted in vivo imaging of integrin alphavbeta6 with an improved radiotracer and its relevance in a pancreatic tumor model. Hausner, SH., Abbey, CK., Bold, RJ., et al.[2022]

A newly engineered cystine knot peptide (knottin) shows high specificity and affinity for the integrin αvβ6, which is important for detecting various cancers, including pancreatic, cervical, and lung cancers, as well as fibrotic lung disease.

The knottin PET tracers were validated in pre-clinical models and demonstrated safety and effective biodistribution in healthy human volunteers, indicating their potential for use in clinical settings for multiple disease states.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of integrin αvβ6 cystine knot PET tracers to detect cancer and idiopathic pulmonary fibrosis. Kimura, RH., Wang, L., Shen, B., et al.[2021]

Citations

1. clinicaltrials.gov clinicaltrials.gov/ct2/keydates/NCT05452005

Fluorine-18-AlphaVBeta6-Binding Peptide Positron ... This study investigates fluorine-18-AlphaVBeta6-BP ([18F]-αvβ6-BP) as a Positron Emission (PET) imaging agent in Non-Small Cell Lung Cancer (NSCLC) patients ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05452005

Study Details | NCT05452005 | Fluorine-18-AlphaVBeta6 ... This study investigates fluorine-18-AlphaVBeta6-BP ([18F]-αvβ6-BP) as a Positron Emission (PET) imaging agent in Non-Small Cell Lung Cancer (NSCLC) patients ...

3. withpower.com withpower.com/trial/phase-1-tumors-metastatic-to-brain-6-2022-16b2f

[18F]-αvβ6-BP PET Imaging for Lung Cancer The integrin αvβ6-binding peptide ([18F]αvβ6-BP) showed excellent selectivity and affinity for its target, allowing for effective noninvasive imaging of various ...

4. studypages.com studypages.com/s/fluorine-18-alphavbeta6-binding-peptide-positron-emission-tomography-in-metastatic-non-small-cell-lung-cancer-418036/

Fluorine-18-AlphaVBeta6-Binding Peptide Positron ... This study investigates fluorine-18-AlphaVBeta6-BP as a Positron Emission (PET) imaging agent in Non-Small Cell Lung Cancer (NSCLC) patients with brain ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6377828/

Preclinical development and first-in-human imaging of the ... PET images showed significant uptake of [18F]αvβ6-BP in both the primary lesion and metastases, including metastasis to brain, bone, liver and lung. Conclusions ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05452005

Study Details | NCT05452005 | Fluorine-18-AlphaVBeta6 ... This study investigates fluorine-18-AlphaVBeta6-BP ([18F]-αvβ6-BP) as a ... [18F]-αvβ6-BP PET/CT to detect αvβ6 positive metastasis in NSCLC, Up to six ...

7. aacrjournals.org aacrjournals.org/clincancerres/article-pdf/doi/10.1158/1078-0432.CCR-18-2665/2119057/1078-0432_ccr-18-2665v1.pdf

Preclinical development and first-in-human imaging of the ... In this respect, our data for [18F]αvβ6-BP indicate a very favorable performance characteristic for identification of small lesions that may be indeterminate on ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9603893/

Integrin Alpha v Beta 6 (αvβ6) and Its Implications in Cancer ... This review explores the αvβ6 integrin biology and its role in healthy humans. We examine the implication of this protein in cancer and its progression.