With a half-life
of 7.45 days, silver-111 (β
max
1.04 MeV,
E
γ
245.4 keV [
I
γ
1.24%],
E
γ
342.1 keV [
I
γ
6.7%]) is a promising
candidate for targeted cancer therapy with
β
–
emitters as well as for associated
SPECT imaging. For its clinical use, the development of suitable ligands
that form sufficiently stable Ag
+
-complexes
in
vivo
is required. In this work, the following sulfur-containing
derivatives of tetraazacyclododecane (cyclen) have been considered
as potential chelators for silver-111: 1,4,7,10-tetrakis(2-(methylsulfanyl)ethyl)-1,4,7,10-tetraazacyclododecane
(DO4S), (2S,5S,8S,11S)-2,5,8,11-tetramethyl-1,4,7,10-tetrakis(2-(methylsulfanyl)ethyl)-1,4,7,10-tetraazacyclododecane
(DO4S4Me), 1,4,7-tris(2-(methylsulfanyl)ethyl)-1,4,7,10-tetraazacyclododecane
(DO3S), 1,4,7-tris(2-(methylsulfanyl)ethyl)-10-acetamido-1,4,7,10-tetraazacyclododecane
(DO3SAm), and 1,7-bis(2-(methylsulfanyl)ethyl)-4,10,diacetic acid-1,4,7,10-tetraazacyclododecane
(DO2A2S). Natural Ag
+
was used in pH/Ag-potentiometric
and UV–vis spectrophotometric studies to determine the metal
speciation existing in aqueous NaNO
3
0.15 M at 25 °C
and the equilibrium constants of the complexes, whereas NMR and DFT
calculations gave structural insights. Overall results indicated that
sulfide pendant arms coordinate Ag
+
allowing the formation
of very stable complexes, both at acidic and physiological pH. Furthermore,
radiolabeling, stability in saline phosphate buffer, and metal-competition
experiments using the two ligands forming the strongest complexes,
DO4S and DO4S4Me, were carried out with [
111
Ag]Ag
+
and promising results were obtained.
