This phase I/II clinical trial evaluates the safety, efficacy, and prognostic potential of [18F]AlF-NOTA-PCP2 PET/CT imaging in assessing PD-L1 expression in malignant tumors, including glioblastoma, head and neck squamous cell carcinoma, non-small cell lung cancer, and esophageal cancer. The primary aim is to establish the correlation between [18F]AlF-NOTA-PCP2 uptake and PD-L1 expression in tumor tissues, while secondary objectives include evaluating its role in predicting clinical outcomes such as progression-free survival (PFS) and overall survival (OS). By providing a non-invasive, quantitative, and reproducible method for assessing PD-L1, this study aims to refine patient stratification and improve the precision of immunotherapy decision-making.

This phase I/II clinical trial is designed to explore the utility of [18F]AlF-NOTA-PCP2 PET/CT in evaluating PD-L1 expression and its prognostic implications in patients with malignant tumors (glioblastoma, head and neck squamous cell carcinoma, non-small cell lung cancer, and esophageal cancer). The study involves at least 20 patients (5 per tumor type) who will undergo a pre-treatment PET/CT scan following an intravenous injection of [18F]AlF-NOTA-PCP2. The primary endpoints include the safety of the imaging protocol and the correlation between [18F]AlF-NOTA-PCP2 uptake (SUV values) and PD-L1 expression determined through immunohistochemistry (IHC). Secondary endpoints explore the dynamic changes in SUV values in patients undergoing multiple scans and their relationship with clinical outcomes.

Scientific and Technical Rationale:

[18F]AlF-NOTA-PCP2 is a novel radiotracer with high specificity for PD-L1, enabling non-invasive imaging of its expression in vivo. This imaging approach complements traditional immunohistochemical methods by offering whole-body assessment, eliminating the need for repeated biopsies, and providing insights into the tumor microenvironment. This study seeks to validate its application in clinical oncology, bridging molecular imaging with biomarker-guided therapeutic strategies.

Study Methods:

Patients will receive a single intravenous dose of [18F]AlF-NOTA-PCP2 (adjusted for body weight), followed by a whole-body PET/CT scan after one hour. Images will be analyzed independently by two experienced nuclear medicine specialists. Tumor biopsies will be collected to measure PD-L1 expression via IHC, and blood samples will be assessed for circulating and exosomal PD-L1 biomarkers. For patients undergoing multiple scans, changes in radiotracer uptake will be tracked to monitor treatment response.

Data Analysis:

SUV values will be correlated with PD-L1 expression levels, clinical factors (e.g., tumor stage, histology), and patient outcomes (PFS, OS). Statistical analyses, performed using SPSS 29.0, will include primary correlations and secondary evaluations of imaging-based dynamic changes and their relationship with therapeutic efficacy.

Significance:

This trial will provide critical data on the feasibility of [18F]AlF-NOTA-PCP2 PET/CT imaging in clinical oncology. Its potential to stratify patients based on PD-L1 expression and predict therapy response could transform personalized cancer care, optimizing immunotherapy outcomes and minimizing unnecessary treatments.

Timeline:

Patient enrollment is expected to last 12 months, with an additional 3 months of follow-up for data collection and analysis.

Inclusion Criteria:

• Signed informed consent obtained.
• Age ≥ 18 years, any gender.
• Pathologically confirmed malignant tumors, including:
• Glioblastoma
• Head and neck squamous cell carcinoma
• Non-small cell lung cancer
• Esophageal cancer
• Detectable PD-L1 expression in tumor tissue (based on immunohistochemistry or biopsy).
• Measurable disease with at least one residual tumor lesion.
• ECOG performance status of 0-1.
• No contraindications to [18F]AlF-NOTA-PCP2 PET/CT imaging.
• Willing and able to comply with study procedures and follow-up visits.

Exclusion Criteria:

• Participation in another interventional clinical trial.
• Failure to recover from toxic effects or complications of prior interventions (≤ grade 1 or baseline levels, excluding fatigue or hair loss).
• Pregnant or breastfeeding women.
• Severe or uncontrolled systemic diseases, including:
• Major, symptomatic arrhythmias or significant ECG abnormalities (e.g., complete left bundle branch block, second-degree or higher heart block, or ventricular arrhythmias).
• Unstable angina or congestive heart failure (NYHA class ≥ 2).
• Any arterial thrombotic or embolic events within 6 months before enrollment (e.g., myocardial infarction, cerebrovascular accident, transient ischemic attack).
• Active or uncontrolled infections requiring systemic treatment.
• Severe psychiatric disorders affecting study participation.
• Any medical history, laboratory abnormality, or condition that may:
• Interfere with study results.
• Affect patient participation.
• Pose an unacceptable risk as determined by the investigator.
• Women of childbearing potential without a negative pregnancy test prior to study entry.
• Known allergy or hypersensitivity to [18F]AlF-NOTA-PCP2 or any component of the radiopharmaceutical.

We plan to share individual participant data (IPD) from this clinical trial, including the following types of data:

Data to be Shared:

Demographic Data: Age, sex, and other basic demographic information. Clinical Data: Diagnosis, treatment regimens, disease stage, and clinical outcomes.

Imaging Data: PET/CT scan images and associated quantitative data (e.g., SUV values) related to [18F]AlF-NOTA-PCP2 uptake.

Biomarker Data: Results from PD-L1 expression assays, including tissue sample data and blood biomarkers.

Adverse Event Data: Adverse event reports, including the type, severity, and outcome as graded by the NCI CTCAE.

How the Data Will Be Shared:

The IPD will be shared via a secure, password-protected database or a data-sharing platform. Access will be granted to qualified researchers upon submission of a data request proposal.

The sharing process will include a data use agreement (DUA) that outlines the terms of use, data protection protocols, and the research purposes for which

Start Date: The IPD and supporting information will be available starting after the completion of the primary analysis and publication of study results, which is expected to be by October 2025.

End Date: The IPD and supporting information will be available for a period of 5 years following study completion, until October 2030.

Who will have access: Access to the individual participant data (IPD) and supporting information will be available to qualified researchers, healthcare professionals, and institutions involved in academic research or related scientific studies. This may include those interested in replicating the study results, conducting further analyses, or exploring the data for new scientific questions.

What will be accessible: Researchers will have access to:

The full individual participant data (IPD), including anonymized data related to clinical outcomes, imaging results (e.g., PET/CT scans), and laboratory tests.

Supporting documents, such as the study protocol, statistical analysis plan (SAP), informed consent form (ICF), and the clinical study report (CSR), which provide details on the methodology, analysis approach, and results.

How to access: Researchers can request access to the IPD and supporting information through the official study contact, Dr. Man Hu (contact: mhu@sdfmu.edu.cn). Upo

This study is open-label, with no masking of any parties involved in the clinical trial. All participants, care providers, investigators, and outcomes assessors are aware of the interventions.