The estrogen receptor (ER) is a target for endocrine therapy in breast cancer patients. Individual quantification of ERα and ERβ expression, rather than total ER levels, might enable better prediction of the response to treatment. We recently developed the tracer 2-¹⁸F-fluoro-6-(6-hydroxynaphthalen-2-yl)pyridin-3-ol (¹⁸F-FHNP) for assessment of ERβ levels with PET. In the current study, we investigated several pharmacokinetic analysis methods to quantify changes in ERβ availability with ¹⁸F-FHNP PET. Methods: Male nude rats were subcutaneously inoculated in the shoulder with ERα/ERβ-expressing SKOV3 human ovarian cancer cells. Two weeks after tumor inoculation, a dynamic ¹⁸F-FHNP PET scan with arterial blood sampling was acquired from rats treated with vehicle or various concentrations of estradiol (nonspecific ER agonist) or genistein (ERβ-selective agonist). Different pharmacokinetic models were applied to quantify ERβ availability in the tumor. Results: Irreversible-uptake compartmental models fitted the kinetics of ¹⁸F-FHNP uptake better than reversible models. The irreversible 3-tissue-compartment model, which included both the parent and the metabolite input function, gave results comparable to those of the irreversible 2-tissue-compartment model with only a parent input function, indicating that radioactive metabolites contributed little to the tumor uptake. Patlak graphical analysis gave metabolic rates (K_i, the irreversible uptake rate constant) comparable to compartment modeling. The K_i values correlated well with ERβ expression but not with ERα, confirming that K_i is a suitable parameter to quantify ERβ expression. SUVs at 60 min after tracer injection also correlated (r² = 0.47; P = 0.04) with ERβ expression. A reduction in ¹⁸F-FHNP tumor uptake and K_i values was observed in the presence of estradiol or genistein. Conclusion: ¹⁸F-FHNP PET enables assessment of ERβ availability in tumor-bearing rats. The most suitable parameter to quantify ERβ expression is the K_i. However, a simplified static imaging protocol for determining the SUVs can be applied to assess ERβ levels.

雌激素受体（ER）是乳腺癌患者内分泌治疗的目标。单独定量ERα和ERβ表达，而不是总ER水平，可以更好地预测对治疗的反应。我们最近开发了示踪剂2- ¹⁸ F-氟-6-（6-羟基萘-2-基）吡啶-3-醇（¹⁸ F-FHNP），用于评估PET的ERβ水平。在当前的研究中，我们研究了几种药代动力学分析方法，以定量¹⁸ F-FHNP PET的ERβ利用率。方法：雄性裸鼠在肩部皮下接种表达ERα/ERβ的SKOV3人卵巢癌细胞。接种肿瘤两周后，动态¹⁸从接受媒介物或各种浓度的雌二醇（非特异性ER激动剂）或染料木黄酮（ERβ选择性激动剂）治疗的大鼠中采集具有动脉血采样的F-FHNP PET扫描。应用了不同的药代动力学模型来量化肿瘤中ERβ的利用率。结果：不可逆吸收区室模型比可逆模型更好地拟合了¹⁸ F-FHNP吸收的动力学。包含母体和代谢物输入功能的不可逆的3组织隔室模型，其结果可与仅具有母体输入功能的不可逆的2组织隔室模型相媲美，表明放射性代谢物对肿瘤的贡献很小摄取。Patlak图形分析给出了代谢率（K _i，不可逆的摄取率常数）可与隔室模型相提并论。所述ķ_我值以及与ERβ表达，但不与ERα相关，确认ķ_我是量化ERβ表达的合适参数。示踪剂注射后60分钟时的SUVs也与ERβ表达相关（r ² = 0.47；P = 0.04）。在存在雌二醇或染料木黄酮的情况下，观察到¹⁸ F-FHNP肿瘤摄取和K _i值降低。结论： ¹⁸ F-FHNP PET能够评估荷瘤大鼠中ERβ的利用率。量化ERβ表达的最合适参数是K _i。但是，用于确定SUV的简化静态成像协议可以应用于评估ERβ水平。