Mathias C J, Welch M J, Katzenellenbogen J A, Brodack J W, Kilbourn M R, Carlson K E, Kiesewetter D O
Int J Rad Appl Instrum B. 1987;14(1):15-25. doi: 10.1016/0883-2897(87)90156-5.
In order to investigate possible correlations between the uptake of 16 alpha-([18F]fluoro)-17 beta-estradiol (18F-ES) by 7,12-dimethylbenz(a) anthracene (DMBA)-induced tumors in rats and the estrogen receptor (ER) content of these tumors, a comprehensive study was performed in which the tissue distribution of 18F-ES was measured in tumor-bearing rats, together with simultaneous measurements of blood volume (by technetium-labeled red blood cells) and blood flow (by iodoantipyrine infusion). In addition, the time course of 18F-ES metabolism and the tissue distribution of the metabolites was studied. Metabolism of 18F-ES is very rapid, and after 2 h, most of the activity in blood and nontarget tissues is due to metabolites; target tissue activity, however, is due mainly to unmetabolized compound. Most of the circulating activity, both 18F-ES and its metabolites, is strongly associated with macromolecules or cells, and while the metabolites are not taken up selectively by target tissues, they do enter nontarget tissues. Tumor blood volume and blood flow vary widely, but not in a way that appears related to tumor necrosis. The uptake of 18F-ES by the uterus and DMBA-induced mammary tumors of adult rats reaches maximum levels (ca 0.35 and 0.10% I.D./g X kg, respectively) at early times (0-1 h), and drops slowly thereafter. The uterus to nontarget or tumour to nontarget tissue ratios, however, start low and continue to increase, reaching maximum levels (ca 20 and 15, respectively) at 2-3 h. There does not, however, appear to be a simple relationship between tumor uptake (either as % I.D./g X kg or tumor to nontarget ratio) measured at a single 3 h time point and tumor ER content, even considering differences in tumor blood flow. This suggests that an estimation of tumor ER content will require the application of more complex pharmacodynamic models that involve the measurement of the complete profile of receptor lignad uptake, retention, and washout from target to nontarget areas. The application of such models will be assisted by the development of estrogen receptor binding ligands that are not converted to circulating metabolites.
为了研究大鼠中7,12 - 二甲基苯并(a)蒽(DMBA)诱导的肿瘤对16α-([18F]氟)-17β-雌二醇(18F - ES)的摄取与这些肿瘤的雌激素受体(ER)含量之间可能存在的相关性，进行了一项全面研究，其中测量了荷瘤大鼠体内18F - ES的组织分布，同时测量了血容量(通过锝标记红细胞)和血流量(通过碘安替比林输注)。此外，还研究了18F - ES的代谢时间进程及其代谢产物的组织分布。18F - ES的代谢非常迅速，2小时后，血液和非靶组织中的大部分活性归因于代谢产物；然而，靶组织中的活性主要归因于未代谢的化合物。大部分循环活性，包括18F - ES及其代谢产物，都与大分子或细胞紧密相关，虽然代谢产物不会被靶组织选择性摄取，但它们会进入非靶组织。肿瘤血容量和血流量差异很大，但与肿瘤坏死的关系不明显。成年大鼠子宫和DMBA诱导的乳腺肿瘤对18F - ES的摄取在早期(0 - 1小时)达到最高水平(分别约为0.35和0.10% ID/g×kg)，此后缓慢下降。然而，子宫与非靶组织或肿瘤与非靶组织的比值开始较低并持续增加，在2 - 3小时达到最高水平(分别约为20和15)。然而，即使考虑肿瘤血流的差异，在单个3小时时间点测量的肿瘤摄取(以% ID/g×kg或肿瘤与非靶组织比值表示)与肿瘤ER含量之间似乎也不存在简单的关系。这表明，估计肿瘤ER含量需要应用更复杂的药效学模型，这些模型涉及测量受体配体从靶区域到非靶区域的摄取、保留和洗脱的完整情况。开发不转化为循环代谢产物的雌激素受体结合配体将有助于此类模型的应用。
