2-(3-{1-Carboxy-5-[(6-[18F]fluoro-pyridine-3-carbonyl)-amino]-pentyl}-ureido)-pentanedioic acid, [18F]DCFPyL, a PSMA-based PET imaging agent for prostate cancer.
2-(3-{1-Carboxy-5-[(6-[18F]fluoro-pyridine-3-carbonyl)-amino]-pentyl}-ureido)-pentanedioic acid, [18F]DCFPyL, a PSMA-based PET imaging agent for prostate cancer.
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DOI：
10.1158/1078-0432.ccr-11-1357
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发表时间：
2011-12-15
期刊：
影响因子：
--
通讯作者：
Pomper MG
中科院分区：
文献类型：
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作者：
Chen Y;Pullambhatla M;Foss CA;Byun Y;Nimmagadda S;Senthamizhchelvan S;Sgouros G;Mease RC;Pomper MG
我们已经合成并在体内评估了2-（3-{1-羧基-5-[（6-[18 F]氟-吡啶-3-羰基）-氨基]-戊基}-脲基）-戊二酸，[18 F]DCFPyL，作为前列腺特异性膜抗原PSMA的潜在成像剂。PSMA在前列腺癌上皮细胞以及大多数实体瘤的新血管中上调。[18 F]DCFPyL由对甲氧基苄基（PMB）保护的lys-C（O）-glu脲前体使用6-[18 F]氟烟酸四氟苯基酯（[18 F]F-Py-TFP）引入18 F以两步合成。放射化学合成后，使用同基因PC 3 PSMA+和PSMA−异种移植模型在免疫功能低下小鼠中进行生物分布和PET成像。使用OLINDA/EXM 1.0计算人体辐射剂量学估计值。DCFPyL显示PSMA的Ki值为1.1 ± 0.1 nM。[18 F]DCFPyL的放射化学产率为36-53%（衰变校正），比放射性为340 - 480 Ci/mmol（12.6 - 17.8 GBq/μmol，n = 3）。在免疫功能低下的小鼠模型中，[18 F]DCFPyL在PET成像上清楚地描绘了PSMA+ PC 3 PIP前列腺肿瘤异种移植物。在注射后2小时，PIP肿瘤内每克组织的注射剂量（%ID/g）为39.4 ± 5.4%，PIP与PSMA− PC 3流感肿瘤内的摄取比例为358：1，位于对侧。在注射后1小时或之后，观察到[18F]DCFPyL的最小非靶组织摄取。膀胱壁是剂量限制器官。这些数据表明[18F]DCFPyL作为一种可行的，新的正电子发射成像剂的PSMA表达组织。
We have synthesized and evaluated in vivo 2-(3-{1-carboxy-5-[(6-[18F]fluoro-pyridine-3-carbonyl)-amino]-pentyl}-ureido)-pentanedioic acid, [18F]DCFPyL, as a potential imaging agent for the prostate-specific membrane antigen, PSMA. PSMA is upregulated in prostate cancer epithelia as well as in the neovasculature of most solid tumors. [18F]DCFPyL was synthesized in two steps from the p-methoxybenzyl (PMB) protected lys-C(O)-glu urea precursor using 6-[18F]fluoronicotinic acid tetrafluorophenyl ester ([18F]F-Py-TFP) for introduction of 18F. Radiochemical synthesis was followed by biodistribution and imaging with PET in immunocompromised mice using isogenic PC3 PSMA+ and PSMA− xenograft models. Human radiation dosimetry estimates were calculated using OLINDA/EXM 1.0. DCFPyL displays a Ki value of 1.1 ± 0.1 nM for PSMA. [18F]DCFPyL was produced in radiochemical yields of 36-53% (decay corrected) and specific radioactivities of 340 – 480 Ci/mmol (12.6 – 17.8 GBq/μmol, n = 3). In an immunocompromised mouse model [18F]DCFPyL clearly delineated PSMA+ PC3 PIP prostate tumor xenografts on imaging with PET. At 2 h post-injection, 39.4 ± 5.4 percent injected dose per gram of tissue (%ID/g) was evident within the PIP tumor, with a ratio of 358:1 of uptake within PIP to PSMA− PC3 flu tumor placed in the opposite flank. At or after 1 h post-injection, minimal non-target tissue uptake of [18F]DCFPyL was observed. The bladder wall is the dose-limiting organ. These data suggest [18F]DCFPyL as a viable, new positron-emitting imaging agent for PSMA-expressing tissues.