CD54-targeted PET for predicting the abscopal effect of local radiotherapy

160 Objectives: Radiotherapy (RT) is used to treat approximately 60% of cancer patients owing to its favorable efficacy in controlling local lesions. The abscopal effect of RT, which was defined as the regression of distant tumors away from the local irradiated lesion, has been proposed for over 60 years. However, this phenomenon is rarely observed in the clinic. Several studies were recently performed to improve the abscopal effect of RT by combining it with other therapeutic strategies such as immunotherapy. In this study, we aimed to investigate whether a PET imaging approach could be used to early predict the abscopal effect of RT towards facilitating the better management of combination therapy. Methods: Bilateral 4T1 tumor-bearing mice were subjected to unilateral RT (3 × 8Gy, every other day), and were then divided into the responsive and nonresponsive groups based on the growth rate of the contralateral (unirradiated) tumors. Proteomics analysis of unirradiated tumors was performed to determine the differences in protein expression between the two groups. PET imaging studies were performed in bilateral tumor-bearing mouse models to determine its role in response prediction of the unirradiated tumors. Results: Proteomics analysis of unirradiated tumors revealed that the expression level of CD54 was significantly higher in the responsive tumors than that in the nonresponsive tumors. In both 4T1 and CT26 bilateral tumor-bearing mouse models, the unirradiated tumors with high CD54 expression as identified by PET imaging using 64Cu-labeled the Fab fragment of an antibody against CD54 (64Cu-αCD54/Fab) showed significantly lower growth rate than that with low CD54 expression. Upregulation of CD54 by intratumoral injection of the constructed adenovirus in the unirradiated tumors significantly inhibited the growth of the unirradiated tumors (P <0.01). Conclusions: The expression level of CD54 positively correlated with the abscopal effect of RT, and upregulation of CD54 could be a powerful strategy to improve this effect. CD54-targeted PET imaging allowed early prediction of the abscopal effect of local radiotherapy in a noninvasive manner.