Malignant tumors pose a grave threat to human health and impose a substantial burden on society. Molecular imaging, which enables non-invasive, in vivo visualization of biological processes at the molecular level, is crucial for early diagnosis and treatment monitoring, thereby improving clinical management. Currently, molecular probes targeting fibroblast activation protein (FAP) and integrin αvβ6, such as ⁶⁸Ga-labeled FAPI and ⁶⁸Ga-Trivehexin, have shown promise in oncologic PET imaging, yet each has limitations.

FAP is predominantly overexpressed in cancer-associated fibroblasts within the tumor stroma, with minimal expression in normal tissues. However, radiotracers like ⁶⁸Ga-FAPI often exhibit physiological uptake in normal organs (e.g., salivary glands, pancreas, uterus), leading to elevated background signals and potentially reduced diagnostic contrast. Conversely, integrin αvβ6 is primarily expressed on tumor cell surfaces and is upregulated in many malignancies. Nonetheless, probes like ⁶⁸Ga-Trivehexin suffer from high renal retention with slow clearance and notable physiological gastrointestinal uptake, resulting in suboptimal target-to-background ratios and compromised image quality.

Given the complementary expression profiles of FAP (stroma) and integrin αvβ6 (tumor cells), we hypothesize that a bispecific molecular probe capable of simultaneously engaging both targets could achieve superior tumor targeting through a synergistic "dual-lock" mechanism. This prospective exploratory clinical trial aims to evaluate the diagnostic efficacy and safety of a novel bispecific probe, named ⁶⁸Ga-B6FA-01, in patients with malignant solid tumors. The ultimate goal is to develop a superior imaging strategy for early and precise tumor diagnosis, treatment response assessment, and personalized therapeutic decision-making.

This investigator-initiated trial (IIT) aims to evaluate the clinical utility of positron emission tomography (PET) imaging targeting both integrin αvβ6 and fibroblast activation protein (FAP) in patients with malignant solid tumors. Based on promising preclinical studies, we have designed and synthesized a bispecific probe, B6FA-01, which can simultaneously bind to both targets. By concurrently targeting two independent, highly expressed targets-one on tumor epithelial cells (αvβ6) and one within the tumor stroma (FAP)-this probe is expected to address the issue of receptor heterogeneity that limits current single-target probes like ⁶⁸Ga-FAPI or ⁶⁸Ga-Trivehexin. Indeed, preclinical data indicate that ⁶⁸Ga-B6FA-01 exhibits not only excellent targeting affinity and specificity but also higher tumor uptake, longer intratumoral retention, faster renal clearance, and a favorable biocompatibility profile compared to its single-target counterparts.

In this prospective study, patients with histologically confirmed malignant solid tumors will undergo ⁶⁸Ga-B6FA-01 PET/CT imaging. Key PET parameters-including the maximum standardized uptake value (SUVmax), mean standardized uptake value (SUVmean), and tumor-to-background ratio (TBR)-will be analyzed to assess their diagnostic performance (sensitivity, specificity, accuracy). Furthermore, the study will explore the correlation between these in vivo imaging parameters and the ex vivo expression levels of αvβ6 and FAP in tumor tissues.

The findings from this study could establish αvβ6- and FAP-targeted PET imaging as a superior, non-invasive tool for tumor diagnosis and treatment assessment.

Inclusion Criteria:

1. Voluntarily provide written informed consent.
2. Age ≥ 18 years.
3. Newly diagnosed with a clinically/radiologically suspected or pathologically confirmed malignant solid tumor, or with suspected recurrence after prior treatment.
4. Eastern Cooperative Oncology Group Performance Status (ECOG PS) score of 0 or 1.
5. Life expectancy > 6 months.
6. Participants of childbearing potential and their partners must agree to use highly effective contraception for 6 months following the last dose of the investigational agent.

Exclusion Criteria:

1. Prior radioisotope therapy within an interval less than 10 times the physical half-life of the respective radionuclide before study administration.
2. Concurrent participation in any other interventional clinical trial.
3. Known allergy or hypersensitivity to the investigational agent or any of its excipients.
4. Inability to lie still for the duration of the PET scan or any condition contraindicating PET imaging.
5. Pregnancy or lactation.
6. Any other condition that, in the investigator's judgment, would compromise participant safety or study integrity.

Eligible participants must voluntarily enroll and provide written informed consent, be aged 18 to 90 years (inclusive) regardless of gender, and have a pathologically confirmed diagnosis of treatment-naïve malignant solid tumors or suspected of having a recurrence after treatment. Additionally, participants must demonstrate willingness and ability to comply with scheduled clinical visits.

The data sharing plan for individual participant data (IPD) from this single-center, investigator-initiated trial has not yet been finalized. The decision will depend on several factors, including the final data governance policies of Zhongnan Hospital of Wuhan University, future intellectual property considerations, and the specific requirements of potential collaborative or publication opportunities. A formal plan will be developed in accordance with institutional guidelines and prevailing best practices for data sharing in clinical research. Data may potentially be made available upon reasonable request and subject to appropriate ethical and administrative approvals.