Optical Imaging with HER2-targeted Affibody Molecules can monitor Hsp90 treatment response in a breast cancer xenograft mouse model
Menée à l'aide de xénogreffes de cancer du sein, cette étude évalue la faisabilité d'une méthode non invasive d'imagerie optique pour suivre in vivo les modifications de l'expression de HER2 en réponse à un traitement par inhibiteur de Hsp90
Purpose: To determine if optical imaging can be used for in vivo therapy response monitoring as an alternative to radionuclide techniques. We evaluated the known Her2 response to 17-DMAG treatment, a Hsp90 inhibitor. Experimental design: After in vitro 17-DMAG treatment response evaluation of MCF7 parental cells and two HER2 transfected clones (Clone A medium, B high Her2 expression), we established human breast cancer xenografts in nude mice for in vivo evaluation. Mice received 120 mg/kg of 17-DMAG in 4 doses at 12h intervals i.p. (n=14), or PBS as carrier control (n=9). Optical images were obtained pre-treatment (day 0) and post-treatment (day 3, 6, and 9), always 5h post-injection of 500 pmol of anti-Her2 Affibody-AlexaFluor680 via tail vein (with pre-injection background subtraction). Day 3 and 9 in vivo optical imaging signal was correlated with ex vivo Her2 levels by western blot. Results: Her2 expression decreased with 17-DMAG dose in vitro. In vivo optical imaging signal was reduced by 22.5% in Clone B (p=0.003) and 9% in MCF7 parental tumors (p=0.23) at 3 days after 17-DMAG treatment; optical imaging signal recovered in both tumor types at day 6-9. In the carrier group no signal reduction was observed. Pearson correlation of in vivo optical imaging signal with ex vivo Her2 levels ranged from 0.73 to 0.89. Conclusion: Optical imaging with an affibody can be used to non-invasively monitor changes in Her2 expression in vivo as a response to treatment with an Hsp90 inhibitor, with results similar to response measurements in PET imaging studies.
Clinical Cancer Research , résumé, 2012