Background: Soluble mesothelin-related peptide (SMRP) is a widely studied tumor marker for diagnosing malignant pleural mesothelioma (MPM). This study discussed the diagnostic value of SMRPs in pleural effusion (PE) for MPM. Methods: Medline, Embase, Web of Science, and Cochrane library system were systematically searched on the data of SMRPs in PE for MPM diagnosis. Pooled diagnostic sensitivity, specificity, and symmetric receiver operating characteristic curve were calculated. Results: Thirteen studies fulfilled the inclusion criteria and a total of 3359 cases including 759 MPM cases, 1061 non-MM (malignant mesothelioma) malignant PE, and 1539 benign PE were brought into this meta-analysis. The pooled results of SMRPs in PE for diagnosing MPM were as follows: sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio were 0.68 (95% confidence interval [CI]: 0.64–0.72), 0.91 (95% CI: 0.86–0.94), 7.8 (95% CI: 5.0–12.0), 0.35 (95% CI: 0.31–0.40), and 22 (95% CI: 14–35), respectively. The area under the summary receiver operating characteristic curves (AUC) was 0.75 (95% CI: 0.72–0.80). Subgroup analyzes revealed that the AUC of cohort group using histological diagnosis could be improved to 0.86 (95% CI: 0.83, 0.89). The Deek's funnel plot asymmetry test showed no publication bias. Conclusion: Although the sensitivity of SMRPs was low, PE-SMRPs can be a good indicator of the existence of MPM.

Mesothelin is a molecular biomarker of many types of solid cancers, which may represent a highly promising new target in the development of cancertargeted diagnostic agents. A human anti-mesothelin antibody with a low molecular weight, ET210sc, was applied; this antibody has potent affinity and can penetrate tissue quickly and stably without causing immunoreactions. We developed a new 124/131 I-labeled radiotracer of ET210sc. The 124/131 I-labeled ET210sc radiotracer showed excellent radiochemical quality (with over 99% radiolabeling yield, 0.07 GBq/μmol specific activity) and remarkable stability in phosphate-buffered saline (>95% at 3 days). The radiotracer retained its potent affinity (dissociation constant, K d = 0.101 nM). The radiotracer specifically bound to mesothelin-positive cells in vitro. Interestingly, the radiotracer exhibited significant positive-tonegative tumor uptake ratios (1.5:1) 3 days postinjection. The estimated absorbed doses of each organ (e.g., 0.704 mGy/MBq for the rectum; 0.341 mGy/MBq for the spleen) met the medical safety standards for further clinical applications. Our findings provide an initial proof of concept for the potential use of 124/131 I-labeled ET210sc radiotracers to detect mesothelin-overexpressing cancer. 124 I-ET210sc is proposed to be an ideal imaging agent for further clinical applications.