Immune checkpoint blockade (ICB) therapy has become a milestone breakthrough in oncology by activating the host immune system to recognize and eliminate tumor cells . Among these, programmed death protein 1 (PD-1) and its ligand (PD-L1) are currently the most widely used targets in clinical practice . However, clinical data indicate that only a subset of patients benefit from anti-PD-1/PD-L1 therapy. Due to the heterogeneity of the tumor microenvironment and the spatiotemporal dynamic changes in PD-L1 expression, traditional tissue biopsy-based detection methods often fail to comprehensively assess disease status, leading to limited treatment response rates . Therefore, there is an urgent need to develop precise strategies for non-invasive, real-time, and dynamic evaluation of PD-L1 expression and treatment response.

Nuclear medicine molecular imaging techniques, particularly positron emission tomography (PET), provide a critical means for non-invasive in vivo visualization of tumor biomarkers . Given the pivotal role of PD-L1 in tumor immune evasion, real-time monitoring of its expression levels is of significant importance for the precise guidance of immunotherapy. In recent years, radiotracer agents based on peptides and small molecules have garnered considerable attention due to their advantages in tissue penetration, rapid blood clearance, and high signal-to-noise ratio imaging. Various PD-L1 probes (e.g., [¹⁸F]BMS-986229, [¹⁸F]AlF-NOTA-IMB) have demonstrated promising application potential in preclinical or clinical studies . Meanwhile, although PD-1/PD-L1 monoclonal antibodies such as nivolumab and atezolizumab have significantly improved treatment outcomes for multiple tumors , they still exhibit inherent limitations in tissue penetration, in vivo clearance rate, imaging background, immunogenicity, and cost. Additionally, PD-L1-targeted therapies alone show limited efficacy in some patients, prompting researchers to further explore novel mechanisms such as protein degradation targeting (PROTAC) to achieve more comprehensive regulation of PD-L1.

Immune checkpoint blockade (ICB) therapy has become a milestone breakthrough in oncology by activating the host immune system to recognize and eliminate tumor cells . Among these, programmed death protein 1 (PD-1) and its ligand (PD-L1) are currently the most widely used targets in clinical practice . However, clinical data indicate that only a subset of patients benefit from anti-PD-1/PD-L1 therapy. Due to the heterogeneity of the tumor microenvironment and the spatiotemporal dynamic changes in PD-L1 expression, traditional tissue biopsy-based detection methods often fail to comprehensively assess disease status, leading to limited treatment response rates . Therefore, there is an urgent need to develop precise strategies for non-invasive, real-time, and dynamic evaluation of PD-L1 expression and treatment response.

Nuclear medicine molecular imaging techniques, particularly positron emission tomography (PET), provide a critical means for non-invasive in vivo visualization of tumor biomarkers . Given the pivotal role of PD-L1 in tumor immune evasion, real-time monitoring of its expression levels is of significant importance for the precise guidance of immunotherapy. In recent years, radiotracer agents based on peptides and small molecules have garnered considerable attention due to their advantages in tissue penetration, rapid blood clearance, and high signal-to-noise ratio imaging. Various PD-L1 probes (e.g., [¹⁸F]BMS-986229, [¹⁸F]AlF-NOTA-IMB) have demonstrated promising application potential in preclinical or clinical studies . Meanwhile, although PD-1/PD-L1 monoclonal antibodies such as nivolumab and atezolizumab have significantly improved treatment outcomes for multiple tumors , they still exhibit inherent limitations in tissue penetration, in vivo clearance rate, imaging background, immunogenicity, and cost. Additionally, PD-L1-targeted therapies alone show limited efficacy in some patients, prompting researchers to further explore novel mechanisms such as protein degradation targeting (PROTAC) to achieve more comprehensive regulation of PD-L1 .

Currently, PROTAC molecular drugs targeting the degradation of disease-related proteins have achieved significant progress in multiple targets, such as Bruton's tyrosine kinase (BTK), androgen receptor (AR), and estrogen receptor (ER) . These molecules achieve efficient regulation of pathogenic protein levels by precisely identifying target proteins and recruiting E3 ubiquitin ligases to initiate ubiquitin-proteasome system-mediated degradation of target proteins. However, existing PROTAC research primarily focuses on therapeutic functions, with in vivo distribution, targeting specificity, and efficacy evaluation still heavily dependent on indirect methods, which limits their clinical translation. Therefore, developing a strategy that can simultaneously achieve "precision molecular imaging" and "targeted therapy" on a single molecular platform holds significant research value. If PET imaging, targeted protein degradation, and radioleukotriene therapy (RLT) are organically integrated into a single molecular system, it would not only enable real-time, quantitative visual monitoring of target expression and drug action processes but also facilitate precision radiotherapy based on this integration. This approach could overcome the limitations of traditional antibody drugs in tissue penetration, imaging-therapeutic synergy, and efficacy prediction, providing a novel molecular design paradigm for precision oncology diagnosis and treatment.

Based on this, the present study designed and constructed a novel multifunctional molecular DOTA-BLP and its radiolabeled derivative ⁶⁸Ga-DOTA-BLP, aiming to achieve dynamic monitoring of PD-L1 using PET imaging. Systematic evaluation in MC38 tumor-bearing mouse models demonstrated that this probe exhibits excellent pharmacokinetic properties and specific imaging capabilities, providing a highly promising solution to address the bottleneck issues in PD-L1-targeted therapy.

Inclusion Criteria:

• Age over 18 years, gender not restricted;
• patients with malignant tumors confirmed by biopsy or surgical pathology;
• Imaging findings of suspicious lymph nodes or distant metastases;
• informed consent signed in writing by the subject or his/her legal guardian.

Exclusion Criteria:

• patients who have received antitumor therapy prior to PET/CT or PET/MR scanning;
• Patients with severe medical conditions who cannot tolerate PET/CT or PET/MR scans;
• The alternative subjects have contraindications to PET/CT or PET/MR scans;
• exposure to radiation of more than 50 mSv in the past year;
• The alternative subjects underwent major surgery within the past 3 months; received experimental drug or device therapy (with unclear efficacy or safety) within the past 1 month;
• The alternative subjects had any clinical conditions that the principal investigator of this study considered to be potentially harmful or associated with the formulation.

Patients with malignant tumors confirmed by biopsy or surgical pathology.