New (68)Ga-PhenA bisphosphonates as potential bone imaging agents.
In vivo positron emission tomography (PET) imaging of the bone using [(68)Ga]bisphosphonates may be a valuable tool for cancer diagnosis and monitoring therapeutic treatment. We have developed new [(68)Ga]bisphosphonates based on the chelating group, AAZTA (6-[bis(hydroxycarbonyl-methyl)amino]-1,4-bis(hydroxycarbonyl methyl)-6-methylperhydro-1,4-diazepine).



Phenoxy derivative of AAZTA (2,2'-(6-(bis(carboxymethyl)amino)-6-((4-(2-carboxyethyl)phenoxy)methyl)-1,4-diazepane-1,4-diyl)diacetic acid), PhenA, 2, containing a bisphosphonate group (PhenA-BPAMD, 3, and PhenA-HBP, 4) was prepared. Labeling of these chelating agents with (68)Ga was evaluated.



The ligands reacted rapidly in a sodium acetate buffer with [(68)Ga]GaCl3 eluted from a commercially available (68)Ge/(68)Ga generator (pH4, >95% labeling at room temperature in 5min) to form [(68)Ga]PhenA-BPAMD, 3, and [(68)Ga]PhenA-HBP, 4. The improved labeling condition negates the need for further purification. The (68)Ga bisphosphonate biodistribution and autoradiography of bone sections in normal mice after an iv injection showed excellent bone uptake.



New (68)Ga labeled bisphosphonates may be useful as in vivo bone imaging agents in conjunction with positron emission tomography (PET).
Five Eleven Pharma Inc., Philadelphia, PA 19104, USA.
Zehui
Z
Wu
Five Eleven Pharma Inc., Philadelphia, PA 19104, USA.
Zhihao
Z
Zha
Five Eleven Pharma Inc., Philadelphia, PA 19104, USA.
Seok Rye
SR
Choi
Five Eleven Pharma Inc., Philadelphia, PA 19104, USA.
Karl
K
Plössl
Five Eleven Pharma Inc., Philadelphia, PA 19104, USA.
Lin
L
Zhu
Five Eleven Pharma Inc., Philadelphia, PA 19104, USA; Department of Radiology, University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address: kunghf@gmail.com.
Hank F
HF
Kung
D000818:Animals; D001842:Bone and Bones / Q000000981:diagnostic imaging* / Q000378:metabolism; D004164:Diphosphonates / Q000737:chemistry* / Q000493:pharmacokinetics; D017886:Durapatite / Q000737:chemistry; D005710:Gallium Radioisotopes; D008297:Male; D051379:Mice; D049268:Positron-Emission Tomography / Q000379:methods*; D011854:Radiochemistry; D051381:Rats; D014018:Tissue Distribution
D004164:Diphosphonates; D005710:Gallium Radioisotopes; D017886:Durapatite
PET imaging agents; biodistribution; gallium-68; tumor