Abstract

(99m)Tc-Annexin A5 has been used as a molecular imaging probe for the visualization, characterization and measurement of apoptosis. In an effort to define the quantitative (99m)Tc-annexin A5 uptake criteria that best predict tumor response to treatment, we performed a systematic review and meta-analysis of the results of all clinical imaging trials found in the literature or publicly available databases.Included in this review were 17 clinical trials investigating quantitative (99m)Tc-annexin A5 (qAnx5) imaging using different parameters in cancer patients before and after the first course of chemotherapy and/or radiation therapy. Qualitative assessment of the clinical studies for diagnostic accuracy was performed using the QUADAS-2 criteria. Of these studies, five prospective single-center clinical trials (92 patients in total) were included in the meta-analysis after exclusion of one multicenter clinical trial due to heterogeneity. Pooled positive predictive values (PPV) and pooled negative predictive values (NPV) (with 95% CI) were calculated using Meta-Disc software version 1.4.Absolute quantification and/or relative quantification of (99m)Tc-annexin A5 uptake were performed at baseline and after the start of treatment. Various quantitative parameters have been used for the calculation of (99m)Tc-annexin A5 tumor uptake and delta (?) tumor changes post-treatment compared to baseline including: tumor-to-background ratio (TBR), ?TBR, tumor-to-noise ratio, relative tumor ratio (TR), ?TR, standardized tumor uptake ratio (STU), ?STU, maximum count per pixel within the tumor volume (Cmax), Cmax%, absolute ?U and percentage (?U%), maximum ?U counts, semiquantitative visual scoring, percent injected dose (%ID) and %ID/cm(3). Clinical trials investigating qAnx5 imaging have included patients with lung cancer, lymphoma, breast cancer, head and neck cancer and other less common tumor types. In two phase I/II single-center clinical trials, an increase of =25% in uptake following treatment was considered a significant threshold for an apoptotic tumor response (partial response, complete response). In three other phase I/II clinical trials, increases of =28%, =42% and =47% in uptake following treatment were found to be the mean cut-off levels in responders. In a phase II/III multicenter clinical trial, an increase of =23% in uptake following treatment was found to be the minimum cut-off level for a tumor response. In one clinical trial, no significant difference in (99m)Tc-annexin A5 uptake in terms of %ID was found in healthy tissues after chemotherapy compared to baseline. In two other clinical trials, intraobserver and interobserver measurements of (99m)Tc-annexin A5 tumor uptake were found to be reproducible (mean difference <5%, kappa?=? 0.90 and 0.82, respectively) and to be highly correlated with treatment outcome (Spearman r?=?0.99, p?

View details for DOI 10.1007/s00259-015-3152-0

View details for Web of Science ID 000363867900017