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

(1)本研究的目的是建立一种新的诊断方法，在体内雌激素受体（ER）的浓度无创测量。(2)16<18>-表雌三醇与氟反应合成16α-氟-17 β-雌二醇（FES）<18>，放化纯度为98.2±0.95%，比活度为36.5±1.25GBq/μ mol。通过将干燥的FES溶解在3.2%吐温、5%乙醇或5%人血清白蛋白的盐水溶液中来制备用于静脉注射的FES溶液。(3)我们研究了FES在未成熟雌性Sprague-Dawley大鼠中的组织分布和动力学。子宫是一种富含ER的组织，其对FES的摄取具有高度选择性，给药后60分钟内最大摄取量为3.29- 5.40%ID/9。同时给予未标记的β-雌二醇可明显抑制子宫FES的摄取。肌肉、ER阴性组织的FES摄取小于0.88%ID/g。(4)全身照射剂量为5.97 × 10 ~ <-6>4 ~ 6.08 × 10 ~ 4<-6>戈伊/MBq。(5)给药后30天内未见不良反应。(6)我们还研究了7，12-二甲基苯并蒽（DMBA）诱发的SD大鼠乳腺肿瘤对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。大鼠乳腺癌对FES的摄取量与体外受体测定的ER浓度呈显著正相关（r=0.45，P&lt;0.05）。(7)这些结果表明，FES摄取的组织主要是ER介导的，因此，FES被认为是有用的非侵入性测量ER浓度在体内的正电子发射断层扫描。

(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.