Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.

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 (Kd = 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.

Original publication

DOI

10.1016/j.nucmedbio.2020.02.014

Type

Journal article

Journal

Nucl Med Biol

Publication Date

05/2020

Volume

84-85

Pages

73 - 79

Keywords

ICAM-1, Pancreatic cancer, SPECT imaging