Evaluation of (4-[18F]Fluorophenyl)triphenylphosphonium ion. A potential myocardial blood flow agent for PET.
OBJECTIVE
The lipophilic cationic compound, (4-[¹⁸F]fluorophenyl)triphenylphosphonium ion (¹⁸F-FTPP) was synthesized and evaluated as a potential positron emission tomography (PET) myocardial perfusion agent.


METHODS
¹⁸F-FTPP was prepared from (4-nitrophenyl)triphenylphosphonium nitrate and ammonium [¹⁸F]fluoride by nucleophilic aromatic substitution and was purified by high performance liquid chromatography before use. Biodistribution studies were performed in rats at 5, 30, 60 min (five rats per time point). Three rats were evaluated by microPET imaging after injection of ¹⁸F-FTPP. In addition, microPET imaging in rabbits (three) was performed before and after occlusion of the left anterior descending (LAD) artery with ¹³NH₃ (111 MBq) and ¹⁸F-FTPP (74 MBq).


RESULTS
Biodistribution data in rats showed rapid blood clearance and high levels of accumulation in the heart; 75:1 heart-to-blood ratio at 30 min. Uptake of radioactivity in the heart was 1.64% ID/G, 1.51% ID/g, and 1.57% ID/g at 5, 30, and 60 min. At 5, 30, and 60 min, lung activity was 0.69% ID/g, 0.03% ID/g, and 0.38% ID/g, and liver uptake was 0.34% ID/g, 0.18% ID/g, and 0.17% ID/g. Heart-to-lung ratios at 5, 30, and 60 min were 2, 5, and 4. Bone accumulation was minimal. MicroPET imaging in both rats and rabbits after injection of ¹⁸F-FTPP demonstrated an initial spike of activity in the myocardium corresponding to blood flow followed by a plateau after 1 min. Region of interest analysis of microPET images of normal and LAD-occluded rabbits with ¹³NH₃ and ¹⁸F-FTPP indicated similar distributions of the two tracers in both normal and altered blood flow regions.


CONCLUSIONS
The excellent heart-to-blood ratio of ¹⁸F-FTPP and its correlation with ¹³NH₃ distribution in normal and LAD-occluded rabbits suggest that this radiopharmaceutical may have potential as a PET agent for characterizing mitochondrial damage and/or myocardial blood flow.
Shoup
Timothy M
TM
Department of Radiology, Massachusetts General Hospital, Edwards Building B015, 55 Fruit Street, Boston, MA, 02114, USA.
Elmaleh
David R
DR
Department of Radiology, Massachusetts General Hospital, Edwards Building B015, 55 Fruit Street, Boston, MA, 02114, USA. delmaleh@partners.org.
Brownell
Anna-Liisa
AL
Department of Radiology, Massachusetts General Hospital, Edwards Building B015, 55 Fruit Street, Boston, MA, 02114, USA.
Zhu
Aijun
A
Department of Radiology, Massachusetts General Hospital, Edwards Building B015, 55 Fruit Street, Boston, MA, 02114, USA.
Guerrero
J Luis
JL
Department of Radiology, Massachusetts General Hospital, Edwards Building B015, 55 Fruit Street, Boston, MA, 02114, USA.
Fischman
Alan J
AJ
Department of Radiology, Massachusetts General Hospital, Edwards Building B015, 55 Fruit Street, Boston, MA, 02114, USA.
D000818:Animals; D003326:Coronary Circulation / Q000502:physiology*; D006321:Heart / Q000000981:diagnostic imaging*; D007275:Injections, Intravenous; D008297:Male; D009943:Organophosphorus Compounds / Q000008:administration & dosage / Q000493:pharmacokinetics; D010477:Perfusion; D010720:Phosphines / Q000008:administration & dosage / Q000493:pharmacokinetics; D049268:Positron-Emission Tomography; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014018:Tissue Distribution
D009943:Organophosphorus Compounds; D010720:Phosphines