An Open-label, Single-arm, Single-center Study to Evaluate the Diagnostic Efficacy of a Novel PET Probe, 68Ga-SFB6-ZN01, in Patients With Malignant Tumors

Study Title An Open-label, Single-arm, Single-center Study to Evaluate the Diagnostic Efficacy of a Novel PET Probe, 68Ga-SFB6-ZN01, in Patients with Malignant Tumors Background and Rationale Integrin αvβ6 is an epithelial-restricted cell surface receptor that is markedly upregulated in various carcinomas (e.g., pancreatic, lung, colorectal, head and neck, breast) during tumorigenesis and metastasis, but is minimally expressed in healthy adult tissues. This expression pattern makes αvβ6 an attractive target for molecular imaging. 68Ga-SFB6-ZN01 is a novel PET radiotracer with high affinity and selectivity for integrin αvβ6. Preclinical studies have demonstrated favorable pharmacokinetics, specific tumor uptake, and acceptable dosimetry. This first-in-human diagnostic study is designed to comprehensively evaluate the clinical performance of 68Ga-SFB6-ZN01 PET/CT.

Study Design This is an open-label, single-center, single-arm, non-randomized, interventional diagnostic study. All enrolled subjects will receive a single intravenous bolus injection of 68Ga-SFB6-ZN01 followed by whole-body PET/CT acquisition. The study is prospective and will be conducted at Zhongnan Hospital of Wuhan University.

Primary Objective and Outcome Measure The primary objective is to determine the diagnostic efficacy of 68Ga-SFB6-ZN01 PET/CT for detecting malignant lesions (primary and metastatic) in patients with proven or suspected solid malignancies. The primary outcome measure is sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV) on a per-patient and per-lesion basis, using histopathology as the gold standard and/or clinical/imaging follow-up of at least 6 months. This outcome will be assessed up to 6 months post-imaging.

Secondary Objectives and Outcome Measures To assess the safety and tolerability of a single microdose of 68Ga-SFB6-ZN01. The corresponding outcome measure is the incidence, severity, and relationship of adverse events, recorded from injection to 72 hours post-injection.

To characterize the biodistribution and estimate radiation dosimetry of 68Ga-SFB6-ZN01. The outcome measures include organ-specific standardized uptake values (SUV), time-activity curves, and effective dose (mSv) calculated from serial whole-body PET/CT scans obtained in a subset of patients over 0-3 hours post-injection.

To evaluate the accuracy of 68Ga-SFB6-ZN01 PET/CT for tumor staging according to the AJCC 8th edition. Outcome measures are the concordance between PET/CT-based stage and histopathology-confirmed stage, as well as the proportion of patients with a change in stage compared to conventional imaging. This will be assessed at baseline.

To explore the correlation between PET semi-quantitative parameters and histopathological features.

Study Population

Approximately 98 eligible subjects will be enrolled. The target population includes:

Patients with histologically confirmed malignant solid tumors (any stage) requiring initial staging or restaging; Patients with high clinical suspicion of malignancy based on conventional imaging and/or elevated tumor markers; Patients with suspected recurrent disease after curative-intent treatment. Inclusion Criteria Voluntary written informed consent. Age ≥ 18 years, male or female. Clinically suspected or pathologically confirmed malignant solid tumor, or suspicion of recurrence after treatment.

Eastern Cooperative Oncology Group performance status (ECOG PS) 0-1. Life expectancy ≥ 6 months. Female subjects of childbearing potential and male subjects with partners of childbearing potential must agree to use highly effective contraception from consent until 6 months after study agent administration.

Exclusion Criteria Administration of any radionuclide within a period less than 10 physical half-lives before study agent injection.

Concurrent participation in another interventional clinical trial involving an investigational drug or device.

Known hypersensitivity to 68Ga-SFB6-ZN01 or any of its excipients. Inability to lie flat or remain still during PET/CT acquisition, or any contraindication to PET/CT.

Pregnancy or breastfeeding. Any other condition that, in the opinion of the investigator, would make the subject unsuitable for participation.

Safety Monitoring Vital signs will be measured before injection and at 30 minutes, 1 hour, and 2 hours post-injection. Adverse events will be recorded throughout the visit.

PET/CT Acquisition Whole-body PET/CT will be performed at 60±10 minutes post-injection. For a subset of approximately 6 patients participating in dosimetry assessments, additional serial PET/CT scans will be obtained at approximately 10, 60, 120, and 180 minutes post-injection.

Image Reconstruction Standard vendor-provided algorithms with attenuation correction, scatter correction, and iterative reconstruction will be used.

Image Analysis Two experienced nuclear medicine physicians, blinded to clinical and histopathological data, will independently interpret all PET/CT images. Discrepancies will be resolved by consensus or a third reader.

Semi-quantitative Parameters For each identified lesion, the following parameters will be recorded: SUVmax, SUVmean, tumor-to-background ratio (TBRmax and TBRmean) using blood pool (aorta) and liver as references, and total lesion metabolism uptake (TLMU) calculated as SUVmean × metabolic tumor volume (MTV).

Staging Tumor-node-metastasis (TNM) stage according to AJCC 8th edition will be assigned based on PET/CT findings and compared with histopathology and/or conventional imaging.

Follow-up Short-term: Subjects will be contacted by telephone or seen in clinic 24-72 hours post-injection to assess for delayed adverse events.

Long-term: Clinical and imaging follow-up data (treatment received, disease status, progression, survival) will be collected at 3, 6, 12, 24, and 36 months as part of standard clinical care. These data will serve as the reference standard for diagnostic accuracy calculations when histopathology is not available.

Reference Standard Primary reference: Histopathology obtained from surgical resection or core needle biopsy, when such tissue is available.

Secondary/composite reference: For lesions without pathological confirmation, a multidisciplinary consensus diagnosis based on at least 6 months of clinical and imaging follow-up (e.g., lesion progression on follow-up imaging, response to therapy, or sustained stability) will be used.

Statistical Considerations Sample Size Justification: The sample size of 98 subjects is based on the precision required for estimating diagnostic sensitivity and specificity. Assuming an expected sensitivity of 90% and specificity of 85% for per-patient diagnosis, a two-sided 95% confidence interval half-width of approximately ±8% is achievable. Accounting for a 10% unevaluable rate, 98 patients provide sufficient precision for the primary endpoint.

Statistical Methods: Diagnostic accuracy: Sensitivity, specificity, PPV, NPV, and accuracy will be calculated with 95% Clopper-Pearson confidence intervals. The area under the receiver operating characteristic curve (AUC) will be estimated.

Ethical Considerations The study will be conducted in full compliance with the Declaration of Helsinki, the International Conference on Harmonisation Good Clinical Practice guidelines, and applicable Chinese regulations. The protocol, informed consent form, and all study-related documents have been reviewed and approved by the Medical Ethics Committee of Zhongnan Hospital, Wuhan University (Approval Number: KELUN[2025106]; Date: November 27, 2025). Written informed consent will be obtained from each participant before any study-specific procedure is performed.