Establishment of a new non-invasive diagnositic method for the breast cancer by measuring in vivo estrogen receptor concentration.

(1)本研究旨在建立一种新的无创检测体内雌激素受体（ER）浓度的诊断方法。(2)通过16-表雌三醇与^<18>F反应合成了16α-[^<18>F]-氟-17β-雌二醇（FES）。FES的放射化学纯度为98.2±0.95%，比活性为36.5±1.25GBq/μ mol。将干燥后的FES分别溶于3.2%吐温、5%乙醇或5%人血清白蛋白的生理盐水中制备静脉注射用FES溶液。(3)观察未成熟雌性sd大鼠FES的组织分布和动力学。子宫作为富含er的组织，摄取FES具有高度选择性，给药后60分钟内最高为3.29- 5.40% ID/9。未标记β-雌二醇联合用药可显著抑制子宫FES摄取。er阴性组织的肌肉对FES的摄取小于0.88% ID/g。(4)全身辐射剂量为5.97 × 10^<-6> ~ 6.08 × 10^<-6> Gy/MBq。(5)给药后30 d内未见不良反应。(6)我们还检测了7,12-二甲基苯(a)蒽（DMBA）诱导的SD大鼠乳腺肿瘤中FES的摄取。给药后60分钟，大鼠乳腺肿瘤对FES的摄取为0.14±0.06% ID/g。大鼠乳腺肿瘤对FES的摄取与体外受体测定的ER浓度呈正相关（r=0.45， P<0.05）。(7)这些结果表明，FES被组织吸收主要是内质网介导的，因此FES被认为可以用于通过正电子发射断层扫描无创测量体内内质网浓度。

(1) The aim of this study is to establish a new diagnostic method to measure the in vivo estrogen receptor (ER) concentration non-invasively.(2) We synthesize 16α-[^<18>F]-fluoro-17β-estradiol (FES) by reacting 16-epiestriol with ^<18>F.Radiochemical purity of FES was 98.2±0.95% and its specific activity was 36.5±1.25GBq/μ mol. The FES solution for intravenous injection was prepared by dissolving the dried FES in 3.2% Tween, 5% ethanol or 5% human serum albumin in saline solution.(3) We examined the tissue distribution and kinetics of FES in immature female Sprague-Dawley rats. The FES uptake by uterus, an ER-rich tissue, was highly selective and it was 3.29-5.40 %ID/9 at maximum within 60 minutes after administration. Coadministration of unlabeled β-estradiol showed marked depression of uterine FES uptake. The FES uptake by muscle, ER-negative tissue, was less than 0.88 %ID/g.(4) The whole body radiation dose were 5.97x10^<-6>〜6.08x10^<-6> Gy/MBq.(5) No side effect was observed durjng 30 days after administration.(6) We also examined the FES uptake in rat breast tumors induced by 7,12-dimethylbenz (a) anthracene (DMBA) in SD rats. The FES uptake by rat breast tumor was 0.14±0.06 %ID/g at 60 minutes after administration. The FES uptake by rat breast tumor s correlated with the ER concentration measured by in vitro receptor assay (r=0.45, P<0.05).(7) These results indicate that the FES uptake by tissue is mainly ER mediated and FES is thus considered to be useful for the non-invasive measurement of ER concentration in vivo by positron emission tomography.