Division of Nuclear Medicine and Molecular Imaging, Boston Children's Hospital, Boston, Massachusetts 02115, USA.
J Med Chem. 2012 Dec 27;55(24):11004-12. doi: 10.1021/jm301453p. Epub 2012 Dec 14.
We recently reported the development of the 2-[(18)F]fluoroethyl ester of rhodamine B as a potential positron emission tomography (PET) tracer for myocardial perfusion imaging. This compound, which was prepared using a [(18)F]fluoroethyl prosthetic group, has significant uptake in the myocardium in rats but also demonstrates relatively high liver uptake and is rapidly hydrolyzed in vivo in mice. We have now prepared (18)F-labeled rhodamine B using three additional prosthetic groups (propyl, diethylene glycol, and triethylene glycol) and found that the prosthetic group has a significant effect on the in vitro and in vivo properties of these compounds. Of the esters prepared to date, the diethylene glycol ester is superior in terms of in vitro stability and pharmacokinetics. These observations suggest that the prosthetic group plays a significant role in determining the pharmacological properties of (18)F-labeled compounds. They also support the value of continued investigation of (18)F-labeled rhodamines as PET radiopharmaceuticals for myocardial perfusion imaging.
我们最近报道了使用 [(18)F]氟乙基前体合成罗丹明 B 的 2-[(18)F]氟乙基酯作为潜在的正电子发射断层扫描 (PET) 心肌灌注成像示踪剂。该化合物在大鼠心肌中有明显摄取，但也显示出相对较高的肝脏摄取，并在小鼠体内迅速水解。我们现在已经使用另外三个前体基团（丙基、二乙二醇和三乙二醇）制备了 (18)F 标记的罗丹明 B，并发现前体基团对这些化合物的体外和体内性质有显著影响。在迄今为止制备的酯中，二乙二醇酯在体外稳定性和药代动力学方面具有优势。这些观察结果表明，前体基团在决定 (18)F 标记化合物的药理学性质方面起着重要作用。它们还支持继续研究作为心肌灌注成像 PET 放射性药物的 (18)F 标记罗丹明的价值。
