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- W2226469439 abstract "1422 Objectives Currently there is limited understanding of bombesin receptor (BB2r) expression in human breast cancer with respect to estrogen receptor (ER) status. This study evaluates the utility of a radiolabeled BB2r antagonist in a panel of 5 human breast cancer cell lines to gain possible insights of the utility of radiolabeled BB2r antagonists to serve as biomarkers and therapeutic agents for breast cancer. Methods DOTA-Amino-Carboxymethyl-Piperidine-DPhe-Gln-Trp-Ala-Val-Gly-His-Sta-Leu-NH2 (EJNMMl 38(1):97, 2011) was radiolabeled with 68Ga and 177Lu. Pharmacokinetic and imaging studies were performed in female SCID mice implanted with human breast tumor cell lines (MB361, MB468, MB231, T47D, and MCF7). PET imaging 1 hour p.i. in mice receiving 2.8-3.7MBq of 68Ga-BB2r antagonist and 7.4-11.1MBq of 18F-FDG on consecutive days was performed. Tumor SUV’s and %ID/g were calculated. Biodistribution studies (1hr p.i.) of 177Lu-BB2r antagonist 0.74-0.92GBq were performed to correlate with imaging data. Results Preclinical PET imaging of 68Ga-BB2r antagonist tumor localization demonstrated targeted uptake in all breast tumor xenograft models. The highest 68Ga-BB2r antagonist SUV’s were observed in ER+ (T47D, MB361, and MCF7) breast cell lines with the mean SUV =0.35 ± 0.26 (n=25) while the two ER- cell line xenografts demonstrated a significantly lower mean SUV =0.09 ± 0.05 (n=16). 18F-FDG PET performed 24 hours post 68Ga imaging revealed no differences between ER+/ER- data with the mean ER+ SUV =0.75 ± 0.27 compared to the mean ER- SUV =0.77 ± 0.22. Similarly, 177Lu-BB2r antagonist tumor uptake at 1 hr p.i. was the highest in the two ER+ models tested (7.12 ± 1.92 %ID/g and 9.58 ± 1.93 %ID/g for MCF7 and T47D xenografts respectively) and markedly lower (1.5±0.5%ID/g) in the ER- MB231 model. Conclusions These preclinical findings suggest that 68Ga-BB2r antagonists may have suitable properties as biomarkers in conjunction with 177Lu-BB2r targeted radiotherapy in breast cancer and their uptake may also directly correlate with estrogen receptor status. Research Support Supported in part by VA Merit BX001699, VA Research Career Scientist Award (TJH)" @default.
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- W2226469439 date "2014-05-01" @default.
- W2226469439 modified "2023-09-29" @default.
- W2226469439 title "Preclinical assessment of a BB2r biomarker for use in breast cancer" @default.
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