@article {Kim384, author = {JinSu Kim and Seonhwa Lee and Sang Moo Lim}, title = {PET and MR evidence of compensatory effects of atorvastatin for cognitive impairment during trastuzumab therapy and enhanced accumulation of trastuzumab in tumor tissue by atorvastatin}, volume = {59}, number = {supplement 1}, pages = {384--384}, year = {2018}, publisher = {Society of Nuclear Medicine}, abstract = {384Introduction: Trastuzumab is the first humanized monoclonal antibody developed for therapeutic use in the treatment of human epidermal growth factor receptor 2 (HER2)-positive cancer. In this study, we first investigated cognitive impairment resulting from trastuzumab therapy, and investigated the mitigation of this impairment following atorvastatin treatment with respect to cerebral glucose metabolism and regional gray matter concentration. In addition, enhanced accumulation of trastuzumab in tumors after atorvastatin treatment was assessed using a HER2-positive gastric cancer model. Methods: Cognitive deficit was modeled using BALB/nude mice, and alopecia was modeled using C57BL/6 mice; 150 μg of trastuzumab (I.V.) and 20 mg/kg of atorvastatin (I.P.) were administrated to observe the effect of this combination therapy on cognitive deficits. To investigate the accumulation and penetration of trastuzumab in the tumors following atorvastatin administration, Alexa-488-trastuzumab was injected (I.V.) and tumors were harvested, flash frozen, and sectioned for immunofluorescence staining and histological imaging. Results: We found a decrease in cerebral glucose metabolism and a decrease in gray matter concentration in the region of the frontal lobe following trastuzumab therapy (P \< 0.005). After subsequent administration of atorvastatin, glucose metabolism and regional gray matter concentration were rescued (P \< 0.005). Further, the penetration and accumulation of trastuzumab in the tumor increased by 100\% after co-administration of atorvastatin. Conclusion: Our study collectively demonstrates that atorvastatin administration with trastuzumab treatment compensates the development of cognitive impairment and enhances the accumulation of trastuzumab in the tumor. These results provide promising evidence to support the therapeutic use of atorvastatin in order to enhance the therapeutic effects of trastuzumab, without cognitive side-effects or hair loss.}, issn = {0161-5505}, URL = {https://jnm.snmjournals.org/content/59/supplement_1/384}, eprint = {https://jnm.snmjournals.org/content}, journal = {Journal of Nuclear Medicine} }