TY - JOUR T1 - Kinetic analysis of 16α-[18F]fluoro-17β-estradiol (FES) in STAT1-/- mammary tumors following treatment with fulvestrant JF - Journal of Nuclear Medicine JO - J Nucl Med SP - 2033 LP - 2033 VL - 52 IS - supplement 1 AU - Kooresh Shoghi AU - Amy Fowler AU - Carmen Dence AU - Dong Zhou AU - Terry Sharp AU - Nicole Fettig AU - S. Chan AU - Robert Schreiber AU - Michael Welch Y1 - 2011/05/01 UR - http://jnm.snmjournals.org/content/52/supplement_1/2033.abstract N2 - 2033 Objectives STAT1 knockout (KO) mice spontaneously develop ER+ luminal mammary tumors. The objective of this work was to analyze the kinetics of FES in STAT1 KO tumors following treatment with Fulvestrant, a selective ERα down-regulator, and validate in-vivo measures against ER binding-capacity (ERBC) analysis. Methods Two STAT1 KO mice received the drug fulvestrant 5mg weekly for 2 weeks while 2 untreated mice received vehicle. Each mouse was imaged with small animal PET and FES for 60min. Five blood samples (10-15μg) were obtained during imaging to characterize FES metabolism. At the conclusion of imaging, mice were sacrificed and tumor extracted for ERBC analysis. Regions of interest (ROI) were drawn on MAP-reconstructed images on the tumor and left-ventricle blood pool (LVBP). The LVBP was validated and used to derive the blood time activity. The metabolite fractions for each mouse were fitted to a sum of 2 exponentials to characterize FES metabolism, which in turn was used to derive a metabolite-corrected input-function (MC-IF) for individual mice. In addition, the average of the metabolite fractions was applied to blood activity of individual mice to test the feasibility of using a population MC-IF (pMC-IF). The classical PET receptor-ligand model with MC-IF or pMC-IF as inputs were used to derive estimates of FES partition coefficient (K1/k2) and receptor density. Results When the pMC-IF was used as an input, fits were not optimal resulting in biased parameter estimates. On average, by 10min 80% of FES was metabolized suggesting that metabolites may confound parameter estimation. When MC-IF was used as input, control mice displayed significantly higher clearance (P=0.0006) and K1/k2 ratio (P=0.03). PET-derived measures of ERα trended with ERBC measures. Conclusions PET measures of ERα density trended with ERBC, though further studies are needed to characterize the influence of metabolites on parameter estimation. Research Support NIH/NCI grants P30CA91842 & U01CA14154 ER -