Granzyme B PET Imaging for Assessment of Disease Activity in Inflammatory Bowel Disease

GZMB as biomarker in IBD for detecting active disease and evaluating treatment response using bioinformatic analysis. (A) Number of significantly altered genes in active UC vs. normal tissues. (B) Upregulated genes that were in common in UC 8 datasets ranked by log₂ fold change. (C) Heat map of up- and downregulated genes in UC and CD tissues compared with normal tissue. (D) Number of altered genes in active CD vs. normal tissues. (E) Upregulated genes that were in common in CD 7 datasets ranked by log₂ fold change. (F) Gene expression of GZMB in patients before and after treatment analyzed by 1-way ANOVA followed by adjusting P value using Benjamini–Hochberg method (data are mean ± SD). (G) Top 15 genes significantly decreased after treatment at different time points (green spots represent top 5 genes, which decreased after treatment, and red represents GZMB). (H) Evaluation of GZMB gene expression in active and inactive UC using t test analysis. FDR = false-discovery rate; log₂FC = log₂ fold change.

(A) Immunofluorescence evaluation of GZMB expression in active IBD. (B) Immunofluorescence evaluation of GZMB expression in quiescent IBD. (C) Quantitative analysis of GZMB to 4′,6-diamidino-2-phenylindole ratio in active IBD vs. quiescent IBD (data are mean ± SEM, 4/group). (D) Hematoxylin and eosin staining of corresponding active IBD samples at indicated magnification. (E) Hematoxylin and eosin staining of corresponding quiescent IBD samples at indicated magnification. Scale bars represent 100 μm. DAPI = 4′,6-diamidino-2-phenylindole.

(A) Coronal representation of ⁶⁸Ga-NOTA-GZP PET imaging patterns alongside CT scans, encompassing both combined PET/CT and standalone PET views in IL10^−/− mice treated with vehicle, DSS, or DSS plus anti-TNF, as well as wild-type animals treated with DSS or vehicle. (B) Representative axial view of ⁶⁸Ga-NOTA-GZP PET/CT uptake pattern in IL10^−/− mice treated with DSS and wild-type mice treated with vehicle. (C) Quantitative analysis of ⁶⁸Ga-NOTA-GZP PET/CT SUV_mean in DSS-treated IL10^−/− mice compared with other groups (7–13/group). (D) ⁶⁸Ga-NOTA-GZP uptake in ex vivo PET/CT imaging experiment of extracted colonic specimens (3/group). (E) Temporal change in ⁶⁸Ga-NOTA-GZP PET/CT uptake during 4 wk after DSS induction (data are mean ± SEM, 8/group). %ID = percentage injected dose; WT = wild-type.