Clinical trial NCT05835570: Integrin αvβ6-targeted PET in Malignant Tumors
Official title: A Single-arm, Open-label, Single-center Clinical Study to the Evaluation of Integrin αvβ6-targeted Positron Emission Tomography (PET) for Malignant Tumors
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Malignant Neoplasm
PET/CT
Non-Small Cell Lung Cancer
Breast Cancer, Metastatic
Keywords: Non-small cell lung cancer
Breast cancer
Integrin-αvβ6
[68Ga]Ga-Trivehexin
Malignant tumors
Lead sponsor: Zhongnan Hospital
Sponsor class: OTHER
First posted: 2023-04-28
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: in-patinets

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.

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.

Primary outcomes:
measure: The diagnostic sensitivity and specificity of 68Ga-Integrin αvβ6 PET/CT in the staging of malignant tumors
timeFrame: 2 years
Secondary outcomes:
measure: Comparison of primary and metastatic lesions between [68Ga]Ga-Trivehexin PET/CT and [18F]FDG PET/CT
timeFrame: 2 years
Other outcomes:
Locations:
city: Wuhan
country: China
facility: Zhongnan Hospital of Wuhan University
state: Hubei
Study officials:
affiliation: Zhongnan Hospital
name: Yong He, MD, PhD
role: PRINCIPAL_INVESTIGATOR
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