Abstract
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Objectives [18F]fluorothymidine (FLT) positron emission tomography (PET) can be useful for measuring in vivo tumor cell proliferation and monitoring response to chemotherapy. This study aimed to determine whether FLT is an effective imaging biomarker to predict response to endocrine therapy using a preclinical mouse model of breast cancer.
Methods FLT and [18F]fluorodeoxyglucose (FDG) PET/CT imaging was performed on female mice bearing SSM3 (hormone-receptor positive STAT1-/-) mammary tumors at baseline and after endocrine therapy with fulvestrant. Tissue FLT biodistribution was performed on untreated female mice bearing SSM3 or SSM1 (hormone-receptor negative STAT1-/-) tumors, male mice bearing CWR22 prostate tumors, and nontumor bearing 129/SvEv, athymic nude, and BALB/c strains of age-matched male and female mice.
Results Treatment with fulvestrant inhibited SSM3 tumor growth and resulted in decreased FDG uptake. In contrast, there was no significant change in FLT uptake of SSM3 tumors in response to endocrine therapy. Tissue FLT biodistribution experiments demonstrated a low, but statistically significant, tumoral (T) uptake compared to muscle (M) in untreated SSM3- and SSM1-tumor bearing mice (T:M 1.5, 1.6; p=0.01) but demonstrated a better T:M of 3.5 in the CWR22 prostate cancer model (p=0.03). FLT biodistribution analysis of nontarget tissues performed on 3 strains of non-tumor bearing mice demonstrated up to 10-fold higher nonspecific uptake in females compared to males.
Conclusions FLT was a better biomarker of proliferation for the CWR22 prostate cancer model than the STAT1-/- breast cancer model. Higher FLT uptake in nontarget tissues observed in females is a contributing factor for the low T:M ratios observed. Thus, FLT may not be a suitable imaging biomarker for all types of breast cancer xenograft models.
Research Support This work was funded by the Mallinckrodt Institute of Radiology at Washington University-St. Louis (MIR 11-037).