Integrin αvβ6-targeted PET in Malignant Tumors

NCT ID: NCT05835570

Last Updated: 2025-04-30

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 200 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2023-01-01
• Study Completion Date: 2025-12-30

Brief Summary

Malignant tumors are a significant health threat with high incidence and mortality rates, and molecular imaging is crucial for early diagnosis, staging, prognosis evaluation, and therapeutic efficacy assessment. 18F-FDG PET imaging is widely used, but has limitations. Integrin αvβ6 is a promising target for tumor-targeted imaging, as it is only expressed in cancerous or reconstructed epithelial cells. A new PET probe, 68Ga-Trivehexin, targeting integrin αvβ6 has been developed with better affinity and selectivity than previous probes. Clinical data supports its safety and metabolic stability, and future research will explore its diagnostic and staging value in different types of tumors, providing a new and precise evaluation method for malignant tumors.

Detailed Description

Malignant tumors are a significant disease that threatens human health and life, with high incidence and mortality rates. Molecular imaging plays an important role in the early diagnosis, staging, prognosis evaluation, and therapeutic efficacy assessment of major diseases such as tumors. Currently, 18F-FDG PET imaging is the most widely used molecular imaging, but there are still problems such as physiological uptake, false negatives, and false positives. It is urgent to explore and develop a new type of tumor-targeting PET imaging.

Integrins are key members of the cell adhesion molecular family and play a central role in regulating cell-cell and cell-extracellular matrix interactions. They are highly expressed in a variety of malignant tumors and plays a vital role in the angiogenesis, invasion and metastasis of tumors, and the regulation of immune microenvironment. As such, integrins have emerged as potential targets for tumor-specific imaging. To date, PET tracers targeting integrin αvβ3 have been extensively studied for imaging tumor neovascularization. However, this integrin subtype also shows certain expression in normal tissue endothelial cells, posing a challenge to its clinical value as a specific marker for tumor imaging. In contrast, integrin αvβ6, another subtype of integrin known as "cancer integrin", is specifically expressed in epithelial-derived tumor cells, whereas it hardly expressed in human healthy tissues. Therefore, integrin αvβ6 has gained attention as an attractive and promising biomarker.

In the past decade, some integrin αvβ6-targeting PET tracers have been synthesized, but these agents have shown relatively low affinity and specificity, with high nonspecific uptake in the gastrointestinal tract, which hinders their clinical translation. Recently, Quigley et al. introduced a novel αvβ6-targeted trimeric probe based on a cyclic peptide c[YRGDLAYp(NMe)K], named 68Ga-Trivehexin. This probe demonstrated favorable characteristics, including excellent targeting affinity (IC50 = 0.047 nM), enhanced tumor uptake, and longer retention time in preclinical study. The preliminary results from PET imaging in 4 cancer patients further demonstrated intense 68Ga-Trivehexin accumulation in head and neck squamous cell carcinoma, parotid adenocarcinoma and pancreatic ductal adenocarcinoma; moreover, there was almost no physiological uptake in normal tissues and organs, such as stomach, intestine, liver, and lung, except for kidney (the excretory organ), resulting in an excellent tumor-to-background ratio.

The safety and metabolic stability of 68Ga-Trivehexin targeting integrin αvβ6 are currently supported by clinical data, and this project will further expand its application in various malignant tumors, clarify its diagnostic and staging value in different types of tumors, and qualitative and quantitative characteristics. This project is expected to provide a new and precise evaluation method for malignant tumors to compensate for the shortcomings of current imaging methods.

Conditions

Malignant Neoplasm; PET/CT; Non-Small Cell Lung Cancer; Breast Cancer, Metastatic

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

Integrin αvβ6-targeted PET in malignant tumors

Participants: newly diagnosed malignant tumor confirmed by pathology or suspected lung cancer. Interventions: Participant who conforms to the inclusion criteria will undergo 18F-FDG and 68Ga-Trivehexin PET/CT scans within 1 week.

Interventions: Participant who conforms to the inclusion criteria will undergo 18F-FDG and 68Ga-Trivehexin PET/CT scans within 1 week.

Objectives: This study aims to assess and compare the diagnostic performance of 68Ga-Trivehexin and 18F-FDG PET/CT for the detection of primary tumors, mediastinal lymph nodes and distant metastases, and to explore the correlation between 68Ga-Trivehexin accumulation and immunohistochemical β6 expression in NSCLC.

PET/CT scans

Intervention Type: DIAGNOSTIC_TEST

Diagnostic Test: For 68Ga-Trivehexin PET/CT, no special preparation was required. Approximately 50 min after an i.v. administration of \[68Ga\]Ga-Trivehexin with a dose of 1.85-2.22 MBq/kg, and the PET acquisition time was 2.5 min per bed.

Interventions

PET/CT scans

Diagnostic Test: For 68Ga-Trivehexin PET/CT, no special preparation was required. Approximately 50 min after an i.v. administration of \[68Ga\]Ga-Trivehexin with a dose of 1.85-2.22 MBq/kg, and the PET acquisition time was 2.5 min per bed.

Intervention Type: DIAGNOSTIC_TEST

Eligibility Criteria

Inclusion Criteria

• Participants with newly diagnosed malignant tumor confirmed by pathology or suspected lung cancer;
• Age ≥18 years, regardless of gender;
• No prior anti-tumor therapy (e.g., chemotherapy, radiotherapy, targeted therapy, or immunotherapy) before PET/CT;
• Eastern Cooperative Oncology Group Performance Status (ECOG PS) score of 0-1;
• Female subjects of reproductive age, male subjects and their partners agree to use reliable contraceptive measures (e.g., abstinence, birth control pills, injectable contraceptives, or subcutaneous contraceptive implants) until 6 months after the completion of the study;
• Participants should voluntarily consent to the clinical trial, and have the ability to understand and sign an informed consent form.

Exclusion Criteria

• Known allergy to injection or its excipients;
• Severe liver or renal dysfunction;
• Claustrophobia or other psychiatric disorders;
• History of other malignant tumors;
• Participation in another clinical trial within 30 days prior to PET/CT scan;
• Pregnant or breastfeeding women;
• Refusal to participate or request for withdrawing from the clinical study;
• Other conditions deemed unsuitable for inclusion by investigator.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Zhongnan Hospital

OTHER

Sponsor Role: lead

Responsible Party

Yong He

Chief of Department of Nuclear Medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Yong He, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Zhongnan Hospital

Locations

Zhongnan Hospital of Wuhan University

Wuhan, Hubei, China

Site Status: RECRUITING

Countries

China

Central Contacts

Yong He, MD, PhD

Role: CONTACT

vincentheyong@163.com

+86-27-67812698

Facility Contacts

Lei Zheng

Role: primary

+86-27-67812787

References

Kimura RH, Wang L, Shen B, Huo L, Tummers W, Filipp FV, Guo HH, Haywood T, Abou-Elkacem L, Baratto L, Habte F, Devulapally R, Witney TH, Cheng Y, Tikole S, Chakraborti S, Nix J, Bonagura CA, Hatami N, Mooney JJ, Desai T, Turner S, Gaster RS, Otte A, Visser BC, Poultsides GA, Norton J, Park W, Stolowitz M, Lau K, Yang E, Natarajan A, Ilovich O, Srinivas S, Srinivasan A, Paulmurugan R, Willmann J, Chin FT, Cheng Z, Iagaru A, Li F, Gambhir SS. Evaluation of integrin alphavbeta6 cystine knot PET tracers to detect cancer and idiopathic pulmonary fibrosis. Nat Commun. 2019 Oct 14;10(1):4673. doi: 10.1038/s41467-019-11863-w.

Reference Type: BACKGROUND

PMID: 31611594 (View on PubMed)

Roesch S, Lindner T, Sauter M, Loktev A, Flechsig P, Muller M, Mier W, Warta R, Dyckhoff G, Herold-Mende C, Haberkorn U, Altmann A. Comparison of the RGD Motif-Containing alphavbeta6 Integrin-Binding Peptides SFLAP3 and SFITGv6 for Diagnostic Application in HNSCC. J Nucl Med. 2018 Nov;59(11):1679-1685. doi: 10.2967/jnumed.118.210013. Epub 2018 Apr 19.

Reference Type: BACKGROUND

PMID: 29674419 (View on PubMed)

Flechsig P, Lindner T, Loktev A, Roesch S, Mier W, Sauter M, Meister M, Herold-Mende C, Haberkorn U, Altmann A. PET/CT Imaging of NSCLC with a alphavbeta6 Integrin-Targeting Peptide. Mol Imaging Biol. 2019 Oct;21(5):973-983. doi: 10.1007/s11307-018-1296-6.

Reference Type: BACKGROUND

PMID: 30671741 (View on PubMed)

Hausner SH, Bold RJ, Cheuy LY, Chew HK, Daly ME, Davis RA, Foster CC, Kim EJ, Sutcliffe JL. Preclinical Development and First-in-Human Imaging of the Integrin alphavbeta6 with [18F]alphavbeta6-Binding Peptide in Metastatic Carcinoma. Clin Cancer Res. 2019 Feb 15;25(4):1206-1215. doi: 10.1158/1078-0432.CCR-18-2665. Epub 2018 Nov 6.

Reference Type: BACKGROUND

PMID: 30401687 (View on PubMed)

Keat N, Kenny J, Chen K, Onega M, Garman N, Slack RJ, Parker CA, Lumbers RT, Hallett W, Saleem A, Passchier J, Lukey PT. A Microdose PET Study of the Safety, Immunogenicity, Biodistribution, and Radiation Dosimetry of 18F-FB-A20FMDV2 for Imaging the Integrin alphavbeta6. J Nucl Med Technol. 2018 Jun;46(2):136-143. doi: 10.2967/jnmt.117.203547. Epub 2018 Feb 2.

Reference Type: BACKGROUND

PMID: 29438002 (View on PubMed)

Van Aarsen LA, Leone DR, Ho S, Dolinski BM, McCoon PE, LePage DJ, Kelly R, Heaney G, Rayhorn P, Reid C, Simon KJ, Horan GS, Tao N, Gardner HA, Skelly MM, Gown AM, Thomas GJ, Weinreb PH, Fawell SE, Violette SM. Antibody-mediated blockade of integrin alpha v beta 6 inhibits tumor progression in vivo by a transforming growth factor-beta-regulated mechanism. Cancer Res. 2008 Jan 15;68(2):561-70. doi: 10.1158/0008-5472.CAN-07-2307.

Reference Type: BACKGROUND

PMID: 18199553 (View on PubMed)

Elayadi AN, Samli KN, Prudkin L, Liu YH, Bian A, Xie XJ, Wistuba II, Roth JA, McGuire MJ, Brown KC. A peptide selected by biopanning identifies the integrin alphavbeta6 as a prognostic biomarker for nonsmall cell lung cancer. Cancer Res. 2007 Jun 15;67(12):5889-95. doi: 10.1158/0008-5472.CAN-07-0245.

Reference Type: BACKGROUND

PMID: 17575158 (View on PubMed)

Debordeaux F, Chansel-Debordeaux L, Pinaquy JB, Fernandez P, Schulz J. What about alphavbeta3 integrins in molecular imaging in oncology? Nucl Med Biol. 2018 Jul-Aug;62-63:31-46. doi: 10.1016/j.nucmedbio.2018.04.006. Epub 2018 May 4.

Reference Type: BACKGROUND

PMID: 29807242 (View on PubMed)

Brzozowska E, Deshmukh S. Integrin Alpha v Beta 6 (alphavbeta6) and Its Implications in Cancer Treatment. Int J Mol Sci. 2022 Oct 15;23(20):12346. doi: 10.3390/ijms232012346.

Reference Type: BACKGROUND

PMID: 36293202 (View on PubMed)

Quigley NG, Steiger K, Hoberuck S, Czech N, Zierke MA, Kossatz S, Pretze M, Richter F, Weichert W, Pox C, Kotzerke J, Notni J. PET/CT imaging of head-and-neck and pancreatic cancer in humans by targeting the "Cancer Integrin" alphavbeta6 with Ga-68-Trivehexin. Eur J Nucl Med Mol Imaging. 2022 Mar;49(4):1136-1147. doi: 10.1007/s00259-021-05559-x. Epub 2021 Sep 24.

Reference Type: BACKGROUND

PMID: 34559266 (View on PubMed)

Wang B, Jiang Y, Zhu J, Wu H, Wu J, Li L, Huang J, Xiao Z, He Y. Fully-automated production of [68Ga]Ga-Trivehexin for clinical application and its biodistribution in healthy volunteers. Front Oncol. 2024 Aug 2;14:1445415. doi: 10.3389/fonc.2024.1445415. eCollection 2024.

Reference Type: DERIVED

PMID: 39156699 (View on PubMed)

Other Identifiers

ZNYYHYXK0003

Identifier Type: -

Identifier Source: org_study_id