18F-labeled rhodamines as potential myocardial perfusion agents: comparison of pharmacokinetic properties of several rhodamines

被引:21
作者
Bartholomae, Mark D. [1 ,2 ]
Zhang, Shaohui [1 ,2 ]
Akurathi, Vamsidhar [1 ,2 ]
Pacak, Christina A. [2 ,3 ]
Dunning, Patricia [1 ]
Fahey, Frederic H. [1 ,2 ]
Cowan, Douglas B. [2 ,3 ]
Treves, S. Ted [2 ,4 ]
Packard, Alan B. [1 ,2 ]
机构
[1] Boston Childrens Hosp, Div Nucl Med & Mol Imaging, Boston, MA 02115 USA
[2] Harvard Univ, Sch Med, Boston, MA 02115 USA
[3] Boston Childrens Hosp, Dept Anesthesiol Perioperat & Pain Med, Boston, MA 02115 USA
[4] Brigham & Womens Hosp, Div Nucl Med & Mol Imaging, Boston, MA 02115 USA
关键词
Fluorine-18; Rhodamine; Myocardial perfusion imaging; PET; POSITRON-EMISSION-TOMOGRAPHY; FLURPIRIDAZ F 18; F-18-FLUOROBENZYL TRIPHENYL PHOSPHONIUM; IMAGING AGENT; PET; F-18; TRACERS; QUANTIFICATION; DISEASE; SAFETY;
D O I
10.1016/j.nucmedbio.2015.06.008
中图分类号
R8 [特种医学]; R445 [影像诊断学];
学科分类号
1002 ; 100207 ; 1009 ;
摘要
Introduction: We recently reported the development of the [F-18]fluorodiethylene glycol ester of rhodamine B as a potential positron emission tomography (PET) tracer for myocardial perfusion imaging (MPI). This compound was developed by optimizing the ester moiety on the rhodamine B core, and its pharmacokinetic properties were found to be superior to those of the prototype ethyl ester. The goal of the present study was to optimize the rhodamine core while retaining the fluorodiethyleneglycol ester prosthetic group. Methods: A series of different rhodamine cores (rhodamine 6G, rhodamine 101, and tetramethylrhodamine) were labeled with F-18 using the corresponding rhodamine lactones as the precursors and [F-18]fluorodiethylene glycol ester as the prosthetic group. The compounds were purified by semipreparative HPLC, and their biodistribution was measured in rats. Additionally, the uptake of the compounds was evaluated in isolated rat cardiomyocytes. Results: As was the case with the different prosthetic groups, we found that the rhodamine core has a significant effect on the in vitro and in vivo properties of this series of compounds. Of the rhodamines evaluated to date, the pharmacologic properties of the F-18-labeled diethylene glycol ester of rhodamine 6G are superior to those of the F-18-labeled diethylene glycol esters of rhodamine B, rhodamine 101, and tetramethylrhodamine. As with F-18-labeled rhodamine B, [F-18]rhodamine 6G was observed to localize in the mitochondria of isolated rat cardiomyocytes. Conclusions: Based on these results, the F-18-labeled diethylene glycol ester of rhodamine 6G is the most promising potential PET MPI radiopharmaceutical of those that have evaluated to date, and we are now preparing to carry out first-in-human clinical studies with this compound. (C) 2015 Elsevier Inc. All rights reserved.
引用
收藏
页码:796 / 803
页数:8
相关论文
共 35 条
[1]   An expedient synthesis of cationic rhodamine fluorescent probes suitable for conjugation to amino acids and peptides [J].
Afonso, CAM ;
Santhakumar, V ;
Lough, A ;
Batey, RA .
SYNTHESIS-STUTTGART, 2003, (17) :2647-2654
[2]  
Akurathi V, 2013, J NUCL MED, V54, P1148
[3]   Effect of the Prosthetic Group on the Pharmacologic Properties of 18F-Labeled Rhodamine B, a Potential Myocardial Perfusion Agent for Positron Emission Tomography (PET) [J].
Bartholomae, Mark D. ;
Gottumukkala, Vijay ;
Zhang, Shaohui ;
Baker, Amanda ;
Dunning, Patricia ;
Fahey, Frederic H. ;
Treves, S. Ted ;
Packard, Alan B. .
JOURNAL OF MEDICINAL CHEMISTRY, 2012, 55 (24) :11004-11012
[4]   Synthesis and applications of Rhodamine derivatives as fluorescent probes [J].
Beija, Mariana ;
Afonso, Carlos A. M. ;
Martinho, Jose M. G. .
CHEMICAL SOCIETY REVIEWS, 2009, 38 (08) :2410-2433
[5]   Cardiac Positron Emission Tomography [J].
Bengel, Frank M. ;
Higuchi, Takahiro ;
Javadi, Mehrbod S. ;
Lautamaki, Riikka .
JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, 2009, 54 (01) :1-15
[6]   Phase II Safety and Clinical Comparison With Single-Photon Emission Computed Tomography Myocardial Perfusion Imaging for Detection of Coronary Artery Disease Flurpiridaz F 18 Positron Emission Tomography [J].
Berman, Daniel S. ;
Maddahi, Jamshid ;
Tamarappoo, B. K. ;
Czernin, Johannes ;
Taillefer, Raymond ;
Udelson, James E. ;
Gibson, C. Michael ;
Devine, Marybeth ;
Lazewatsky, Joel ;
Bhat, Gajanan ;
Washburn, Dana .
JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, 2013, 61 (04) :469-477
[7]   Improvement in PET myocardial perfusion image quality and quantification with flurpiridaz F 18 [J].
Berman, Daniel S. ;
Germano, Guido ;
Slomka, Piotr J. .
JOURNAL OF NUCLEAR CARDIOLOGY, 2012, 19 :S38-S45
[8]  
Elmaleh D, 2009, J NUCL MED, V50
[9]   Biodistribution and stability studies of [18F]Fluoroethylrhodamine B, a potential PET myocardial perfusion agent [J].
Gottumukkala, Vijay ;
Heinrich, Tobias K. ;
Baker, Amanda ;
Dunning, Patricia ;
Fahey, Frederic H. ;
Treves, S. Ted ;
Packard, Alan B. .
NUCLEAR MEDICINE AND BIOLOGY, 2010, 37 (03) :365-370
[10]   Synthesis of fluorine-18 labeled rhodamine B: A potential PET myocardial perfusion imaging agent [J].
Heinrich, Tobias K. ;
Gottumukkala, Vijay ;
Snay, Erin ;
Dunning, Patricia ;
Fahey, Frederic H. ;
Treves, S. Ted ;
Packard, Alan B. .
APPLIED RADIATION AND ISOTOPES, 2010, 68 (01) :96-100