RT Journal Article
SR Electronic
T1 Non-invasive PET imaging of downregulation of HER-2 in 17-DMAG treated ovarian cancers
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 455
OP 455
VO 50
IS supplement 2
A1 Niu, Gang
A1 Li, Zibo
A1 Chen, Xiaoyuan (Shawn)
YR 2009
UL http://jnm.snmjournals.org/content/50/supplement_2/455.abstract
AB 455 Objectives 17-DMAG, a heat shock protein 90 (Hsp90) inhibitor, has been intensively investigated for cancer therapy and is undergoing clinical trials.HER-2 is one of the client proteins of Hsp90 and its expression decreases upon 17-DMAG treatment. In this study, we aimed to non-invasively monitor the HER-2 response to 17-DMAG treatment in xenografted mice. Methods The sensitivity of human ovarian cancer SKOV3 cells to 17-DMAG was measured by MTT assay. HER-2 expression of SKOV3 cells after treated with different doses of 17-DMAG was determined by flow cytometry. Nude mice bearing SKOV3 tumor were injected intraperitoneally with 17-DMAG (3 × 50 mg/kg) and then imaged with microPET using 64Cu-DOTA- trastuzumab. Biodistribution studies, immunofluorescence staining were performed to validate the microPET results. Results SKOV3 cells are sensitive to 17-DMAG treatment in a dose dependent manner, with an IC50 value of 68.7 nM at 72 h. Quantitative microPET imaging studies showed that 64Cu-DOTA-trastuzumab has prominent tumor activity accumulation in untreated SKOV3 tumors (33.90 ± 7.82 %ID/g; n = 4), but significantly lower uptake in 17-DMAG treated tumors (11.74 ± 4.23 %ID/g; n = 4), at 24 h p.i.. There were no significant differences in other major organ uptake with or without 17-DMAG treatment based on microPET imaging and biodistribution studies. Immunofluorescence staining confirmed the significantly lower EGFR expression level in the tumor tissue upon 17-DMAG treatment. Conclusions The early response to anti-Hsp90 therapy was successfully monitored by quantitative PET using 64Cu-DOTA-trastuzumab. This approach would be valuable in monitoring the therapeutic response in HER-2-positive cancer patients under 17-DMAG treatment.