Che
lates are an important part of meta
l based radiopharmaceutica
ls. This study examines the possib
le app
lication of phosphonate ester moieties incorporated into che
lates, where the ester group can be changed to modu
late the pharmacokinetics of the radiopharmaceutica
l, whi
le the phosphonate stab
ly binds the meta
l radioisotope. Two phosphonate ester containing che
lates, PCTMB and PCTM(F)E, were compared to the carboxy
late containing ana
logue,
p-Bn-PCTA, with respect to radiochemistry with severa
l radionuc
lides (In-111, Ga-68, Ga-67, Cu-64). The phosphonate ester derivatives were simi
lar to
p-Bn-PCTA with respect to efficient radio
labe
ling with each of the radiometa
ls under mi
ld, aqueous conditions. Each of the radio
labe
led phosphonate esters was a
lso shown to be stab
le under physio
logica
l conditions
in vitro. The phosphonate ester moieties did exhibit a propensity to degrade under more acidic conditions. Biodistribution studies in mice with the In-111 radio
labe
led versions of PCTMB, PCTM(F)E and
p-Bn-PCTA demonstrated the abi
lity of the phosphonate ester functiona
lities to change the pharmacokinetics of the BFCs. With increasing
lipophi
licity, the phosphonate ester derivatives showed increasing hepatic c
learance; but no significant increase in background tissue uptake (bone, musc
le) was observed, and a
ll the In-111 radio
labe
led BFCs were substantia
lly c
leared within 24 h. The substitution of phosphonate ester for carboxy
late functiona
l groups in che
lates may be an effective strategy to assist in optimizing the pharmacokinetics of radiopharmaceutica
ls through varying of the ester group.
Keywords:
lates&qsSearchArea=searchText">chelates;
pharmacokinetics;
lear+imaging&qsSearchArea=searchText">nuclear imaging;
Ga-68;
Cu-64;
In-111