Abstract 2778: Mapping the extracellular pH gradient of colorectal cancer after immuno-thermal ablation

Abstract

Abstract Background: Biosensor imaging of redundant deviation in shifts (BIRDS) is a non-invasive MR imaging modality that maps extracellular pH (pHe) by directly detecting paramagenetically shifted non-exchangeable protons of exogeneous agents. Previously it has been used to characterize various tumors in the rat brain and to monitor the response to loco-regional treatment of liver cancer. The purpose of this study was to investigate the feasibility of utilizing pHe mapping with BIRDS to differentiate ablated and non-ablated tumors in the setting of systemic immunotherapy of murine colorectal cancer (CRC). Materials and Methods: Eight BALB/c mice (Charles River Laboratories, Wilmington, MA, USA) were implanted with bilateral flank injections of 0.5 × 106 CT26.WT colorectal cancer cells (CRL- 2638; ATCC, Manassas, VA). Mice were randomly assigned into 3 treatment groups; group 1 received injections of sham antibodies (InVivoMAb IgG controls), group 2 was treated with dual anti-PD-1 and anti-CTLA-4 antibodies (Clone J43 & Clone 9D9; BioXcell, West Lebanon, NH, USA), III). Group 3 received cryoablation in combination with systemic injections of dual checkpoint inhibitors. Mapping of pHe was performed between 3-10 days after the initiation of treatment and was immediately followed by sacrifice. Results: The mean pHe of untreated, control tumors was significantly lower than the average pHe of tumors treated with immuno-thermal ablations (6.6 vs 6.96; p<0.05). Among the mice in the ablation groups, the targeted tumors demonstrated significantly less acidity on average than the distal, off-target tumors (6.96 vs 6.63; p<0.05). The average pHe of tumors in the DICB group was not significantly different than any other group (6.75 vs 6.6, 6.96 & 6.63; p>0.05). Conclusions: BIRDS MR quantification was feasible for imaging murine CRC model. BIRDS quantification of pHe could serve as an imaging non-invasive biomarker for metabolic changes of the tumor microenvironment in a murine CRC model with Immuno-Thermal Ablation Therapy. Significance at a GlanceTreatment GroupMean Extracellular pHSignificant DifferencesControl6.6Vs Target Ablated Tumors (p<0.05)Dual Immune Checkpoint Blockade (DICB)6.75NoneTargeted tumors in Ablated group6.96Vs Control (p<0.05) Vs Off-target Tumors (p<0.05)Off-target tumors in Ablated Group6.63Vs Ablated Tumors (p<0.05) Citation Format: Ryan J. Slovak, Daniel Coman, Johannes M. Ludwig, Hyun S. Kim. Mapping the extracellular pH gradient of colorectal cancer after immuno-thermal ablation [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2778.