Immuno-imaging of ICAM-1 in tumours by SPECT

Abstract

Purpose: Molecular imaging of cancer cells' reaction to radiation damage can provide a non-invasive measure of tumour response to treatment. The cell surface glycoprotein ICAM-1 (CD54) was identified as a potential radiation response marker. SPECT imaging using an ¹¹¹In-radiolabelled anti-ICAM-1 antibody was explored.

Methods: PSN-1 cells were irradiated (10 Gy), and protein expression changes were investigated using an antibody array on cell lysates 24 h later. Results were confirmed by western blot, flow cytometry and immunofluorescence. We confirmed the affinity of an ¹¹¹In-labelled anti-ICAM-1 antibody in vitro, and in vivo, in PSN-1-xenograft bearing mice. The xenografts were irradiated (0 or 10 Gy), and [¹¹¹In]In-anti-ICAM-1 SPECT/CT images were acquired 24, 48 and 72 h after intravenous administration.

Results: ICAM-1 was identified as a potential marker of radiation treatment using an antibody array in PSN-1 cell lysates following irradiation, showing a significant increase in ICAM-1 signal compared to non-irradiated cells. Western blot and immunohistochemistry confirmed this upregulation, with an up to 20-fold increase in ICAM-1 signal. Radiolabelled anti-ICAM-1 bound to ICAM-1 expressing cells with good affinity (K_d = 24.0 ± 4.0 nM). [¹¹¹In]In-anti-ICAM-1 uptake in tumours at 72 h post injection was approximately 3-fold higher than non-specific isotype-matched [¹¹¹In]In-mIgG2a control (19.3 ± 2.5%ID/g versus 6.3 ± 2.2%ID/g, P = 0.0002). However, ICAM1 levels, and [¹¹¹In]In-anti-ICAM-1 uptake in tumours was no different after irradiation (uptake 9.2%ID/g versus 14.8%ID/g). Western blots of the xenograft lysates showed no significant differences, confirming these results.

Conclusion: Imaging of ICAM-1 is feasible in mouse models of pancreatic cancer. Although ICAM-1 is upregulated post-irradiation in in vitro models of pancreatic cancer, it shows little change in expression in an in vivo mouse xenograft model.

Keywords: ICAM-1; Pancreatic cancer; SPECT imaging.