Development of a radiolabeled site-specific single-domain antibody positron emission tomography probe for monitoring PD-L1 expression in cancer / 药物分析学报

Despite advances in immunotherapy for the treatment of cancers,not all patients can benefit from programmed cell death ligand 1(PD-L1)immune checkpoint blockade therapy.Anti-PD-L1 therapeutic effects reportedly correlate with the PD-L1 expression level;hence,accurate detection of PD-L1 expression can guide immunotherapy to achieve better therapeutic effects.Therefore,based on the high affinity antibody Nb109,a new site-specifically radiolabeled tracer,68Ga-NODA-cysteine,aspartic acid,and valine(CDV)-Nb109,was designed and synthesized to accurately monitor PD-L1 expression.The tracer 68Ga-NODA-CDV-Nb109 was obtained using a site-specific conjugation strategy with a radiochemical yield of about 95％and radiochemical purity of 97％.It showed high affinity for PD-L1 with a dissociation constant of 12.34±1.65 nM.Both the cell uptake assay and positron emission tomography(PET)imaging revealed higher tracer uptake in PD-L1-positive A375-hPD-L1 and U87 tumor cells than in PD-L1-negative A375 tumor cells.Meanwhile,dynamic PET imaging of a NC1-H1299 xenograft indicated that doxorubicin could upregulate PD-L1 expression,allowing timely interventional immunotherapy.In conclusion,this tracer could sensitively and dynamically monitor changes in PD-L1 expression levels in different cancers and help screen patients who can benefit from anti-PD-L1 immunotherapy.

Pharmacokinetic and imaging evaluation of 99mTc-HBIDP as a potential bone imaging agent

Developing novel superior bone-seeking radiopharmaceutical for the detection of malignant bone lesions could further improve the diagnostic value of routine bone scanning and shorten the interval between injection and imaging. In order to further evaluate the bone imaging efficiency of 99mTc-HBIDP [1-hydroxy-2-[1-butyl-imidazol-2-yl]-ethane-1, 1-diphosphonic acid], the pharmacokinetic in mice and single photon emission computed tomography [SPECT] bone scanning in rabbit for 99mTc-HBIDP was investigated. Kinetics of blood clearance showed that the distribution half-life [T1/2a] and elimination half-life [T1/2] of 99mTc-HBIDP are 2.73 and 24.87 min, respectively. Excellent bone images can be obtained at 1 h post injection with SPECT bone scanning, which is clearer and quicker than 99mTc-ZL [zoledronate] and 99mTc-MDP [methylenediphosphonate]. All results indicate that 99mTc-HBIDP holds great potential as a novel improved bone imaging agent