Journal: JCI Insight

Article Title: Priming is key to effective incorporation of image-guided thermal ablation into immunotherapy protocols

doi: 10.1172/jci.insight.90521

Figure Lengend Snippet: (A–F) Tumor permeability of proteins after thermal ablation was assessed in vivo by tracking Copper-64–labeled BSA (64Cu-BSA) with positron emission tomography at (A) 0.5, (B) 6, (C) 18, (D) 24, and (E) 48 hours. A single tumor in a bilateral NDL tumor–bearing mouse was ablated (white arrow). Also visible are contralateral tumors (red arrow). Tracer kinetics and biodistribution were plotted for the (F) maximum intratumoral accumulation of 64Cu-BSA versus time, revealing a temporal peak of the spatial mean and maximum occurring at 6 hours after injection (n = 4 per cohort, data are mean ± SEM). (G and H) Increased vascularization of the tumor-draining lymph node 0.5 hours after tumor ablation upon H&E histological staining (n = 3). Scale bar: 300 μm. (G) Draining lymph node following thermal ablation with green box at location of interest. (H) View of enhanced vascularization within the lymph node indicated by green arrows. (I–N) Tumor permeability to small molecules after thermal ablation was assessed in vivo with contrast enhanced T1-weighted magnetic resonance imaging (CET1wMRI) (n = 3). (I) Gadoteridol was administered immediately before (J) ablation (red arrow). (K) Gadoteridol accumulated in the ablated region 3 hours after injection and ablation. (L) Contrast was readministered at 3 hours; additional accumulation was not detected. (M) At 20 hours after injection and ablation, intratumoral gadoteridol accumulation had cleared. (N) After 20 hours, gadoteridol readministration resulted in accumulation in the surrounding tumor rim (blue arrows) but not within in the ablated tissue. (O–Q) Mechanisms for enhanced accumulation 48 hours after thermal ablation with H&E (n = 8). (O) Representative tumor following ablation with green and red box at locations of interest. Scale bar: 3 mm. (P) Image from red box of heat-fixed tissue with shrunken but intact nuclei and preservation of tissue architecture (black arrow) surrounded by discohesive and nonviable tumor tissue with some ghosted nuclei and local edema (yellow arrow). Scale bar: 60 μm. (Q) Image from green box of inflammation observed, where leukocytes are densely located in the periphery of the tumor (yellow arrows). Scale bar: 60 μm.

Article Snippet: Prior to MRgFUS, mice were given 0.05–0.1 mg/kg buprenorphine s.c. and 0.05 mmol/kg of gadoteridol (Bracco Imaging) via i.p. injection.

Techniques: Permeability, In Vivo, Labeling, Positron Emission Tomography, Injection, Staining, Magnetic Resonance Imaging, Preserving