Pharmacokinetic assessment of the uptake of 16beta-18F-fluoro-5alpha-dihydrotestosterone (FDHT) in prostate tumors as measured by PET.
Pharmacokinetic assessment of the uptake of 16beta-18F-fluoro-5alpha-dihydrotestosterone (FDHT) in prostate tumors as measured by PET.
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DOI：
10.2967/jnumed.109.066159
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发表时间：
2010-02
期刊：
影响因子：
--
通讯作者：
Humm JL
中科院分区：
文献类型：
--
作者：
Beattie BJ;Smith-Jones PM;Jhanwar YS;Schöder H;Schmidtlein CR;Morris MJ;Zanzonico P;Squire O;Meirelles GS;Finn R;Namavari M;Cai S;Scher HI;Larson SM;Humm JL
本研究的目的是开发一种临床可用的非侵入性方法，以18F-FDHTPET为基础，定量前列腺癌患者治疗期间雄激素受体(AR)水平的变化。13名患者在选定的肿瘤上进行了动态18F-FDHTPET扫描。同时采集静脉血进行血液代谢物分析。另一组为25名患者，注射了18F-FDHT，并进行了心脏动态PET成像。这些数据被用来生成基于总体的输入函数，这对于药代动力学建模是必不可少的。在肿瘤组织数据上对增加复杂性的线性房室药代动力学模型进行了检验。使用贝叶斯信息准则(BIC)对四种合适的模型进行了应用和比较。模型1由一个瞬时平衡空间和一个单向陷阱组成。模型2a和2b包含瞬时平衡空间和陷阱之间的可逆空间，代谢物被排除(2a)或允许(2b)进入。模型3建立在模型2b的基础上，在单向陷阱之前增加了第二个可逆空间，并从中排除了代谢物。18F-FDHT在血液中的半衰期被测定为6-7分钟。因此，前列腺癌病变对18F-FDHT的摄取在20分钟内达到平台期，因为血液传播的活动被消耗掉了。在CWR22细胞的体外研究中，放射性标记的代谢物被证明不与AR结合。模型1对所有数据集都产生了合理且稳健的拟合，并且在26次肿瘤扫描中有16次被BIC评为最佳。模式2a、模式2b和模式3分别在7个、2个和1个案例中被评为最佳。我们的研究探索了使用18F-FDHTPET估计游离AR浓度的临床潜力。这一过程包括对净摄取参数的估计，如模型1‘S KTRAP，它可以作为转移性前列腺癌AR表达的替代测量。我们的初步研究表明，简单的体重归一化标准摄取值(SUV)与基于模型的KTRAP估计有很好的相关性，我们推测KTRAP估计可能与AR表达成正比。检验这一假设的验证研究正在进行中。
The aim of this study was to develop a clinically applicable non-invasive method to quantify changes in androgen receptor (AR) levels based on 18F-FDHT PET in prostate cancer patients undergoing therapy. Thirteen patients underwent dynamic 18F-FDHT PET scans over a selected tumor. Concurrent venous blood samples were acquired for blood metabolite analysis. A second cohort of 25 patients, injected with 18F-FDHT underwent dynamic PET imaging of the heart. These data were used to generate a population-based input function, essential for pharmacokinetic modeling. Linear compartmental pharmacokinetic models of increasing complexity were tested on the tumor tissue data. Four suitable models were applied and compared using the Bayesian Information Criterion (BIC). Model 1 consisted of an instantaneously equilibrating space followed by a unidirectional trap. Models 2a and 2b contained a reversible space between the instantaneously equilibrating space and the trap, into which metabolites were excluded (2a) or allowed (2b). Model 3 built upon Model 2b with the addition of a second reversible space preceding the unidirectional trap and from which metabolites were excluded. The half-life of the 18F-FDHT in blood was determined to be between 6-7 minutes. As a consequence, the uptake of 18F-FDHT in prostate cancer lesions reached a plateau within 20-minutes as the blood-borne activity was consumed. Radiolabeled metabolites were shown not to bind to AR in in-vitro studies with CWR22 cells. Model 1 produced reasonable and robust fits for all datasets and was judged best by the BIC for 16 out of 26 tumor scans. Models 2a, 2b and 3 were judged best in seven, two and one case, respectively. Our study explores the clinical potential of using 18F-FDHT PET to make estimates of free AR concentration. This process involved the estimation of a net-uptake parameter such as Model 1’s ktrap that could serve as a surrogate measure of AR expression in metastatic prostate cancer. Our initial studies suggest a simple body-mass normalized standard uptake value (SUV) is reasonably well correlated to model based ktrap estimates, which we surmise may be proportional to AR expression. Validation studies to test this hypothesis are underway.
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影响因子：
7.3
作者：
CHOE, YS;LIDSTROM, PJ;KATZENELLENBOGEN, JA
通讯作者：
KATZENELLENBOGEN, JA
影响因子：
2.8
作者：
Fedoruk, MN;Giménez-Bonafé, P;Nelson, CC
通讯作者：
Nelson, CC
影响因子：
4
作者：
Chen, Yu;Sawyers, Charles L.;Scher, Howard I.
通讯作者：
Scher, Howard I.
DOI：
10.1007/s00259-005-1764-5
发表时间：
2005-03-01
影响因子：
9.1
作者：
Dehdashti, F;Picus, J;Welch, MJ
通讯作者：
Welch, MJ