FabRICATOR® presents F(ab’)2 PET-tracers for Prognostic Imaging

March 18, 2020 | References |

Scientists at Minerva Imaging demonstrate the use of FabRICATOR® to generate a 64Cu-labeled F(ab’)2 PET-tracer for the detection of changes in T Cell response to combined radiation and immunoblockade therapy.
 

Current immunotherapy response-evaluation criteria are limited in discriminating responsive patients eligible for immunotherapy from non-responders. Accurate evaluations of progression are limited by pseudo-progression, a phenomenon where therapy-induced inflammatory events temporarily increase tumor volume, thereby delaying evidence of response. Routine and standardized clinical evaluations are needed that require predictive biomarkers combined with reproducible methods for monitoring biomarker expression and dynamics.
 

Targeting T cells as essential players in the anti-tumor immune response, Kristensen et al. developed a 64Cu-labeled F(ab’)2 against murine CD8a+ T cells. The scientists further demonstrate its potential as a prognostic PET-imaging biomarker

for immunotherapy response in mouse models of colorectal cancer. Rat anti-mouse CD8a antibodies were digested using the FabRICATOR enzyme to generate homogenous F(ab’)2 and Fc/2 subunits. Purification by preparative HPLC yielded isolated F(ab’)2 subunits for random chelation with p-SCN-Bn-NOTA and radiolabeling using the 64Cu isotope. Treatment response assessment was conducted using in vivo PET-imaging of tumor-bearing mice subjected to combined radiation and anti-CTLA-4 therapy.
 

The scientists found that the tumor-to-heart ratio of the PET-tracer increased with combined therapy, this was also confirmed by flow cytometry and IHC analysis showing increased tumor infiltration by CD8+ T cells. The prognostic value of the PET-tracer was further demonstrated using in vivo imaging as the scientists were able to distinguish responsive mice from non-responders prior to treatment-induced variations in tumor volume.
 

Kristensen et al., 2020. Monitoring CD8+ T Cell Responses to Radiotherapy and CTLA-4 Blockade Using [64Cu]NOTA-CD8a PET imaging. Mol Imaging Biol (2020).