Abstract
PurposeMolecular 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. MethodsPSN-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. ResultsICAM-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. ConclusionImaging 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.
Highlights
Radiotherapy (RT) using ionizing radiation (IR) is an essential component of treatment for more than half of all newly diagnosed cancer patients, in whom it can irreversibly damage targeted tumour cell DNA to reduce tumour size [1]
ICAM-1 protein expression is upregulated in PSN-1 cells following irradiation
The cell surface protein ICAM-1 showed a marked and significant increase (Fig. 1A, B). This was confirmed by western blot on an independent set of cell lysates (Fig. 1C), demonstrating a 4.7 and a 20-fold increase in ICAM-1 expression 24 or 48 h after irradiation, respectively
Summary
Radiotherapy (RT) using ionizing radiation (IR) is an essential component of treatment for more than half of all newly diagnosed cancer patients, in whom it can irreversibly damage targeted tumour cell DNA to reduce tumour size [1]. Tumour response to treatment varies between patients and anatomical changes may not be measurable using anatomical imaging techniques such as CT or MRI, for a significant period following treatment [3]. This will impact on the timely need to consider changes to treatment in order to improve patient outcome, should the treatment prove non-efficacious. Number of molecular biomarkers that guide clinical decisions following radiation therapy [4,5], especially those imaging extracellular epitopes to facilitate imaging This highlights the need for alternative imaging biomarkers
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