Acyclic chelate with ideal properties for (68)Ga PET imaging agent elaboration.
We have investigated novel bifunctional chelate alternatives to the aminocarboxylate macrocycles NOTA (N(3)O(3)) or DOTA (N(4)O(4)) for application of radioisotopes of Ga to diagnostic nuclear medicine and have found that the linear N(4)O(2) chelate H(2)dedpa coordinates (67)Ga quantitatively to form [(67)Ga(dedpa)](+) after 10 min at RT. Concentration-dependent coordination to H(2)dedpa of either (68)Ga or (67)Ga showed quantitative conversion to the desired products with ligand concentrations as low as 10(-7) M. With (68)Ga, specific activities as high as 9.8 mCi nmol(-1) were obtained without purification. In a 2 h competition experiment against human apo-transferrin, [(67)Ga(dedpa)](+) showed no decomposition. Two bifunctional versions of H(2)dedpa are also described, and these both coordinate to (67)Ga at RT within 10 min. Complete syntheses, characterizations, labeling studies, and biodistribution profiles of the (67)Ga complexes are presented for the new platform chelates. The stability of these platform chelates is higher than that of DOTA.
Medicinal Inorganic Chemistry Group, Department of Chemistry, University of British Columbia, 2036 Main Mall, Vancouver, British Columbia V6T 1Z1, Canada.
Eszter
E
Boros
Cara L
CL
Ferreira
Jacqueline F
JF
Cawthray
Eric W
EW
Price
Brian O
BO
Patrick
Dennis W
DW
Wester
Michael J
MJ
Adam
Chris
C
Orvig
D000818:Animals; D002614:Chelating Agents / Q000737:chemistry*; D005710:Gallium Radioisotopes; D006571:Heterocyclic Compounds / Q000737:chemistry; D006573:Heterocyclic Compounds, 1-Ring; D006801:Humans; D015394:Molecular Structure; D049268:Positron-Emission Tomography / Q000379:methods*
D002614:Chelating Agents; D005710:Gallium Radioisotopes; D006571:Heterocyclic Compounds; D006573:Heterocyclic Compounds, 1-Ring; C048993:1,4,7-triazacyclononane-N,N',N''-triacetic acid