Breast cancer models to study the expression of estrogen receptors with small animal PET imaging

Different animal models of estrogen positive tumors (ER+) were evaluated for their suitability to follow tumor response after various treatment protocols, using small animal positron emission tomography (PET). ER+ human breast cancer cell lines MCF-7 and T-47D, using MDA-MB-231 as ER-; control, and murine mammary ductal carcinomas MC4-L2, MC4-L3, and MC7-L1, were compared for their in vivo growth rate and retention of ER+ status. Tumor metabolic activity was estimated from the relative uptake (% injected dose/g) of [F-18]fluorodeoxyglucose (FDG) uptake, whereas ER content was determined from 16alpha-[F-18]fluoroestradiol (FES) retention. F-18 activity values were obtained by small animal PET imaging and confirmed by tissue sampling and radioactivity counting. Reliable uptake measurements could be obtained for tumors of 200 mul or over. The human cell lines grew at a slower rate in vivo and failed to accumulate FES; in contrast, the Balb/c MC7-L1 and MC4-L2 grew well and showed good uptake of both FDG and FES. Chemotherapy and hormone therapy delayed the growth of MC7-L1 and MC4-L2 tumors, confirming their suitability as an ER+ model for therapeutic interventions. MC4-L3 tumors also showed promising results but required the presence of progestative pellets to grow. These data demonstrate that murine MC7-L1 and MC4-L2 tumors are suitable models for the monitoring of ER+ breast cancer therapy using small animal PET imaging. (C) 2004 Elsevier Inc. All rights reserved.