Peptide-based PET tracer targeting LAG-3 for evaluating the efficacy of immunotherapy in melanoma.

BACKGROUND: Lymphocyte activation gene 3 (LAG-3) is expressed on activated immune cells and has emerged as a promising target for immune checkpoints blockade. However, conflicting findings have been reported regarding the association between LAG-3 expression in tumors and patient prognosis, indicating the need for further investigation into the significance of LAG-3 expression levels in tumor therapies. In this study, 68Ga-NOTA-XH05, a novel peptide-based positron emission tomography (PET) tracer targeting LAG-3, was constructed to non-invasively detect LAG-3 expression in melanoma after CpG oligonucleotide (CpG) treatment and explore the relationship between LAG-3 expression and therapeutic effect. METHODS: The tracer 68Ga-NOTA-XH05 was identified by high-performance liquid chromatography after being prepared and purified. Cell uptake and blocking essays were performed to verify the specificity of the tracer in vitro. The expression of LAG-3 in B16-F10 subcutaneous tumors was monitored by flow cytometry, and its correlation with the tracer uptake was analyzed to evaluate the tracer specificity. PET imaging and biodistribution studies were conducted after CpG treatment of unilateral or bilateral B16-F10 subcutaneous tumor models to assess the ability of 68Ga-NOTA-XH05 in monitoring immunotherapy efficacy and the abscopal effect of CpG. RESULTS: Following purification, 68Ga-NOTA-XH05 exhibited high radiochemical purity and specificity. Flow cytometry analysis revealed a positive correlation between LAG-3 expression in tumors and the uptake of 68Ga-NOTA-XH05. In B16-F10 bearing mice treated with CpG, PET imaging using 68Ga-NOTA-XH05 demonstrated a higher tumor to blood ratio (TBR) compared with the control group. Furthermore, TBR values obtained from CpG-treated mice allowed for differentiation between responders and non-responders. In a bilateral subcutaneous tumor model where only right-sided tumors were treated with intratumoral injection of CpG, TBR values of left-sided tumors were significantly higher than those in the control group, indicating that 68Ga-NOTA-XH05 could effectively monitor the systemic effect of local CpG injection. CONCLUSION: Our findings highlight the detection capability of 68Ga-NOTA-XH05 in assessing LAG-3 expression levels within tumors and evaluating response to immunotherapy, thereby suggesting promising clinical translational prospects.

Rosin modified cellulose nanofiber as a reinforcing and co-antimicrobial agents in polylactic acid /chitosan composite film for food packaging.

Cellulose nanofiber (CNF) was modified by rosin and used as a reinforcement filler within a polylactic acid (PLA) matrix. The resulting film was then coated with chitosan (CHT) to prepare a two-layer composite film for antimicrobial food packaging. The FT-IR spectra of rosin modified CNF (R-CNF) displayed a clear peak at 1730cm-1, which confirmed the successful esterification of CNF by rosin. The R-CNF showed a better dispersion in PLA matrix than CNF and the loading of R-CNF had a significant effect on the mechanical properties of the resulting film. A percolation network was formed when the R-CNF loading was 8%, where the composite film displayed optimum mechanical properties. The antimicrobial test showed that the R-CNF/PLA/CHT composite film exhibited excellent antimicrobial performance against E. coli and B. subtilis, which could be attributed to the synergistic antimicrobial effect of CHT and rosin.