Evaluation of the Diagnostic Efficacy of a αvβ6/FAP-Targeting Heterodimeric Probe in Patients With Malignant Solid Tumors

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.

Sex

All

Minimum age

18 Years

Maximum age

90 Years

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.

• BACKGROUNDZang J, Wen X, Lin R, Zeng X, Wang C, Shi M, Zeng X, Zhang J, Wu X, Zhang X, Miao W, Xu P, Guo Z, Zhang J, Chen X. Synthesis, preclinical evaluation and radiation dosimetry of a dual targeting PET tracer [68Ga]Ga-FAPI-RGD. Theranostics. 2022 Oct 9;12(16):7180-7190. doi: 10.7150/thno.79144. eCollection 2022. PMID 36276644