67Ga-9N3 uptake by xenografts of human melanotic melanoma in mice

Structural and in vivo studies of metal chelates of Ga(III) relevant to biomedical imaging

“…Besides proving the high in vivo stability of these chelates, this study also illustrated how the biodistribution and excretion properties of complexes injected into the blood stream are influenced by their molecular size, molecular weight, charge and hydrophilicity [12,13]. Other examples are found in the literature of very stable complexes of 67 Ga with triazamacrocycles containing different pendant arms, conferring to some of them different biodistribution and clearance pathways [14][15][16]. High liver uptake was found for 2nitroimidazole conjugates of 67 Ga(NOTA) [16], as opposed to 67 Ga(NOTA), and its tris(methylenemethylphosphinic acid) analogue, 67 Ga(NOTMP) [14,15].…”

“…Thus, they can be used as a sensitive measure of that degree of distortion in solution, corrected for changes of the rotational correlation time [16,26]. Based on the solution NMR and X-ray crystal data, such a relative degree of distortion can be proposed as: Ga(NOTA) ; Ga(NODASA) ; Ga(NOTMP) -Ga(NOTP) 3y -Ga(NOTPP) < Ga(NOTBzP) < Ga(DETA) < Ga(DOTRA) < Ga(UNTA) ( 71 Ga signal linewidth is 3500 Hz for Ga(DOTRA) and no signal is observed for Ga(UNTA) [8]; UNTA is 1,4,7-triazacycloundecane-1,4,7-triacetate, DOTRA is 1,4,7-triazacyclododecane-1,4,7-triacetate [14]). The large 69 Ga signal linewidth of Ga(NODASA) relative to the X-ray defined octahedral distortion [23] results in part from a slower rotation of the chelate caused by the uncoordinated, heavily hydrated, bcarboxylate bound to one of the acetate arms of the NOTAtype structure, and also from the somewhat larger quadrupolar moment of the 69 Ga isotope relative to 71 Ga [26].…”

“…Other examples are found in the literature of very stable complexes of 67 Ga with triazamacrocycles containing different pendant arms, conferring to some of them different biodistribution and clearance pathways [14][15][16]. High liver uptake was found for 2nitroimidazole conjugates of 67 Ga(NOTA) [16], as opposed to 67 Ga(NOTA), and its tris(methylenemethylphosphinic acid) analogue, 67 Ga(NOTMP) [14,15]. Some hypoxic tumour localization was also found for both 67 Ga(NOTA) and its 2-nitroimidazole conjugate [15].…”

Nuclear magnetic resonance, luminescence and structural studies of lanthanide complexes with octadentate macrocyclic ligands bearing benzylphosphinate groups

“…Experiments involving nude male mice bearing the HX 118 melanotic melanoma xenograft followed the methods and practices set out previously. 35,36…”

“Bite like a Rottweiler”

“…The resulting (1,4,7‐triazacyclononane‐1,4,7‐triyl)triacetic acid (NOTA) became widely known as the prototype of NOTA‐like ligands, an entirely new class of chelators named after its parent structure. A few years later, research on this motif was pursued by Parker and co‐workers, who characterized its complex with gallium(III)16 and investigated the biodistribution of the corresponding 67 Ga‐labeled compound 17. Encouraged by the outstanding kinetic inertness of Ga III –NOTA chelates, they synthesized NOTA derivatives with various linkers on the macrocycle backbone as well as on side chain methylene groups, and proposed an application in 67 Ga radiopharmaceuticals, namely labeled antibodies 18…”