Immunotherapy blocking programmed cell death protein 1/programmed death ligand 1 (PD-1/PD-L1) pathway has achieved great therapeutic effect in the clinic, but the overall response rate is not satisfactory. Early studies showed that response to treatment and overall survival could be positively related to PD-L1 expression in tumors. Therefore, accurate measurement of PD-L1 expression will help to screen cancer patients and improve the overall response rate. A small molecular positron emission tomography (PET) probe [18F]LP-F containing a biphenyl moiety was designed and synthesized for measurement of PD-L1 expression in tumors. The PET probe [18F]LP-F was obtained with a radiochemical yield of 12.72 ± 1.98%, a radiochemical purity of above 98% and molar activity of 18.8 GBq/μmol. [18F]LP-F had good stability in phosphate buffer saline (PBS) and mouse serum. In vitro assay indicated that [18F]LP-F showed moderate affinity to PD-L1. Micro-PET results showed that the tumor accumulation of [18F]LP-F in A375 tumor was inferior to that in A375-hPD-L1 tumor. All the results demonstrated that [18F]LP-F could specifically bind to PD-L1 and had a potential application in non-invasive evaluation of PD-L1 expression in tumors.
Integrin αvβ6 has been considered as a promising
biomarker for lung cancer, and its expression is often related to
poor prognosis. An αvβ6-binding
cystine knot peptide R01-MG was previously engineered and
validated. Here, we developed a positron emission tomography (PET)
probe of R01-MG for imaging αvβ6-positive lung cancer. Cystine knot peptide R01-MG
was synthesized through solid-phase peptide synthesis chemistry and
radiolabeled with 68Ga after being conjugated with 1,4,7,10-tetraazacyclododecane-N,N′,N″,N‴-tetraacetic acid (DOTA). The stability of 68Ga-DOTA-R01-MG was analyzed in phosphate-buffered
saline (PBS) (pH 7.4) and fetal bovine serum (FBS). The cell uptake
assay of the probe was evaluated using αvβ6-positive (A549 and H1975) and αvβ6-negative (H1299) lung cancer cell lines. In addition, small
animal PET imaging and biodistribution studies of 68Ga-DOTA-R01-MG were performed in αvβ6-positive and αvβ6-negative lung
cancer models. Our study showed that 68Ga-DOTA-R01-MG exhibited excellent stability in PBS and FBS. Small animal PET
imaging and biodistribution data revealed that 68Ga-DOTA-R01-MG displayed rapid and good tumor uptake in animal models
with αvβ6-positive lung cancer,
and the probe was rapidly cleared from the normal tissues, resulting
in good tumor-to-normal tissue contrasts. Meanwhile, no obvious tumor
uptake of 68Ga-DOTA-R01-MG was observed in animal
models with αvβ6-negative lung cancer,
demonstrating specific binding of the probe to integrin αvβ6. In conclusion, 68Ga-DOTA-R01-MG has great potential to be a promising PET tracer for
imaging αvβ6-positive lung cancer.
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