RT Journal Article
SR Electronic
T1 New 68Ga AAZTA-bisphosphonates as potential bone imaging agents.
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 1380
OP 1380
VO 57
IS supplement 2
A1 Wu, Zehui
A1 Zha, Zhihao
A1 Choi, Seok
A1 Ploessl, Karl
A1 Zhu, Lin
A1 Kung, Hank
YR 2016
UL http://jnm.snmjournals.org/content/57/supplement_2/1380.abstract
AB 1380Objectives In vivo positron emission tomography (PET) imaging of the bone using [68Ga] bisphosphonates may be a valuable tool for cancer diagnosis and monitoring therapeutic treatment. Previously, [68Ga]BPAMD, [68Ga]1, has been reported as a useful PET imaging agent for studying bone metastasis in cancer patients. We have developed new AAZTA (6-[bis(hydroxycarbonyl-methyl)amino]-1,4-bis(hydroxycarbonyl methyl)-6-methylperhydro-1,4-diazepine derivatives labeled with 68Ga ([68Ga]2, [68Ga]3 and [68Ga]4) as new bone targeting agents.Methods 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) were prepared. Labeling of these chelating agents with 68Ga was evaluated.Results The ligands reacted rapidly with [68Ga]GaCl3 eluted from a commercially available 68Ge/68Ga generator (pH 4, >95% room temperature in 5 min) to form [68Ga]PhenA-BPAMD, 3, and [68Ga]PhenA-HBP, 4. Formation of the complexes was not effected by the presence of Zn2+, Cu2+, Fe3+ and Sn2+ (< 100 uM). The improved labeling condition negates the need for further purification. The 68Ga PhenA derivatives ([68Ga]2, [68Ga]3 and [68Ga]4) showed superb in vivo stability. Biodistribution of [68Ga]3 and [68Ga]4 showed excellent bone uptake in normal mice; as expected, the agent without the bisphosphonate group, ([68Ga]2, showed no bone uptake. Autoradiography of bone sections of mice confirmed the uptake was concentrated at active bone surfaces.Conclusions New 68Ga bisphosphonates, [68Ga]3 and [68Ga]4, may be useful as bone imaging agents in conjunction with positron emission tomography (PET).