pd-l1 pet imaging in patients with the immunotherapy for non-small cell lung cancer

Conditions: NSCLC Stage IV; PD-L1 Gene Amplification

Summary: clinical trials have shown efficacy of pd1/pd-l1 checkpoint inhibitors in multiple solid tumors, including nsclc. whole body information with regard to target presence, drug kinetics and dynamics, as well as binding of pd-l1 targeting agents to the immune system cells is lacking.molecular imaging of pd-l1 could lead to new insights on heterogeneity of pd-l1 expression in metastatic lesions and be of help in the prediction of response to pd1/pd-l1 inhibitors in a noninvasive manner.

immunohistochemistry (ihc) is currently the most commonly used method for evaluation of pd-l1 status in cancer patients,including nsclc. however, biopsies are spatiotemporally limited because of the highly heterogeneous expression of pd-l1. only 20-40% of pd-l1-positive patients respond to treatment, while 10% of pd-l1-negative patients show a good response to immune checkpoint inhibitors .patients with false-negative pd-l1 results may miss the chance for targeted therapy.additionally, the pd-l1 status can change dynamically during the disease process.therefore, it is necessary to achieve higher response rates, lower toxicity and lower treatment costs by finding assays to better assess pd-l1 expression and screen patients for benefit. pd-l1 pet imaging provides a new approach to assess pd-l1 expression in nsclc patients and is expected to overcome the limitations of immunohistochemical ,detection of pd-l1 expression for dynamic visualization in primary and metastatic tumors . first, pet imaging can provide multidimensional three-dimensional data of overall pd-l1 expression in tumors. second, the whole-body pd-l1 expression level can be assessed, and the heterogeneity of pd-l1 expression between tumors can be studied simultaneously. third, it is non-invasive and provides information on pd-l1 expression not only before treatment, but also allows monitoring pd-l1 expression several times during treatment ,to screen patients for benefit and guide treatment. currently, the fda-approved 68ga/68gagenerator is commercially available, and the cyclotron can produce 68ga on a large scale. also, the 68ga labeling technology is mature. therefore, 68ga-pdl1 pet imaging is more easily translatable to the clinical setting. a previous study reported the synthesis and preclinical evaluation of 68ga-bms986192, including pd-l1 affinity, metabolic stability, micro pet imaging and in vivo biodistribution in pd-l1 positive and negative transplanted tumors, demonstrating the feasibility of this tracer for in vivo imaging of tumor pd-l1 expression.

Eligibility criteria:
inclusion criteria: * (1) subjects must be diagnosed with histologically confirmed stage iv non-small cell lung cancer and \>18 years of age with driver mutations (-). (2) planned for anti-pd-1/pd-l1 therapy. (3) at least one easy accessible lesion of which a biopsy can be taken within one month prior to pet scan. (4) subjects must sign informed consent prior to inclusion in this trial. exclusion criteria: - (1) female patients during pregnancy and lactation. (2) patients with psychiatric disease, severe hepatic and renal insufficiency. (3) patients who refuse anti-pd-1/pd-l1 therapy. (4) patients who are claustrophobic or unable to undergo pet/ct examination. (5) prior treatment with an anti-pd-1, anti-pd-l1, anti-pd-l2 antibody, or any other antibody or drug specifically targeting t-cell costimulation or immune checkpoint pathways, except anti-ctla4 antibody. (6) those who, in the opinion of the investigator, are otherwise unsuitable for clinical trials.