van Waarde A, Anthonio R L, Visser T J, Elsinga P H, Posthumus H, Weemaes A M, Blanksma P K, Visser G M, Paans A M, Vaalburg W
Positron Emission Tomography (PET) Center, University Hospital, Groningen, Netherlands.
J Chromatogr B Biomed Appl. 1995 Jan 20;663(2):361-9. doi: 10.1016/0378-4347(94)00442-8.
beta-Adrenoceptors in human lungs and heart can be imaged with the radioligand 4-[3-[(1,1-dimethylethyl)amino]-2-hydroxypropoxy]-1,3- dihydro-2H-benzimidazol-2-11C-one (CGP 12177, [11C]I). For quantification of receptor density with compartment models by adjustment of rate constants, an 'input function' is required which consists of the integral of the concentration of unmodified ligand in arterial plasma over time. A discrepancy in the literature regarding metabolic stability of [11C]I prompted us to study metabolism in rats by reversed-phase HPLC (RP-HPLC) of trichloroacetic acid extracts of arterial plasma after i.v. injection of [11C]I (> 11.1 TBq/mmol, 11 MBq/kg). Some plasma samples were also directly applied to an internal-surface reversed-phase (ISRP) column. In parallel experiments, tritiated [11C]I was employed and methanol extracts of arterial plasma were analyzed by straight-phase TLC. The three methods were in excellent agreement. Unmodified [11C]I decreased from > 98.5% (3H) or > 99.9% (11C) initially to 57 +/- 7% at 80 min post injection due to formation of two polar metabolites. Using the RP-HPLC method, no metabolism was detectable in humans up to 30 min after injection of [11C]I (1851 MBq). Deproteinization of plasma with acetonitrile resulted in the formation of a radioactive species (artifact) which eluted immediately after the void volume in RP-HPLC and which could be mistakenly interpreted as a metabolite. Plasma protein binding was low (ca. 30%) in both humans and rats.(ABSTRACT TRUNCATED AT 250 WORDS)
人肺和心脏中的β-肾上腺素受体可用放射性配体4-[3-[(1,1-二甲基乙基)氨基]-2-羟基丙氧基]-1,3-二氢-2H-苯并咪唑-2-酮（CGP 12177，[¹¹C]I）进行成像。为了通过调整速率常数用房室模型定量受体密度，需要一个“输入函数”，它由动脉血浆中未修饰配体浓度随时间的积分组成。文献中关于[¹¹C]I代谢稳定性存在差异，这促使我们通过反相高效液相色谱法（RP-HPLC）研究大鼠静脉注射[¹¹C]I（>11.1 TBq/mmol，11 MBq/kg）后动脉血浆三氯乙酸提取物的代谢情况。一些血浆样品也直接应用于内表面反相（ISRP）柱。在平行实验中，使用了氚标记的[¹¹C]I，并通过正相薄层层析法分析动脉血浆的甲醇提取物。这三种方法结果高度一致。由于形成了两种极性代谢物，未修饰的[¹¹C]I最初从>98.5%（³H）或>99.9%（¹¹C）在注射后80分钟降至57±7%。使用RP-HPLC方法，在注射[¹¹C]I（1851 MBq）后长达30分钟的人体中未检测到代谢。用乙腈使血浆脱蛋白会导致形成一种放射性物质（假象），它在RP-HPLC中于空体积后立即洗脱，可能会被错误地解释为代谢物。人及大鼠的血浆蛋白结合率均较低（约30%）。（摘要截短于250字）
