Characterization of 111In3+ complexes of DTPA amide derivatives: biodistribution and clearance studied by gamma imaging

Abstract

A large series of structurally related diethylenetriaminepentaacetic acid amide derivatives with different structures and lipophilic properties were synthesized and radiolabeled with (111)In(3+). Two of the more hydrophobic compounds studied ([(111)In]L(9) and [(111)In]L(10)) showed high affinity for human serum albumin (HSA). The biodistribution and clearance properties shown by all complexes upon injection in Wistar rats were followed by gamma imaging. The blood retention time of the chelates correlates better with their binding to HSA than with their hydrophilic/lipophilic ratio. Hydrophilic and negatively charged complexes undergo renal retention, while the majority of the lipophilic complexes are retained in the blood for a longer period of time and are cleared through the liver.

Color Doppler Ultrasound and Gamma Imaging of Intratumorally Injected 500 nm Iron–Silica Nanoshells

“…Only 2 hours after intravenous administration of 111 In-DTPA the largest retained dose was found in the kidneys, which only retained an average 0.126 % injected dose/ gram. 38 Li et al . found that when studying the biodistribution of 111 In-DTPA in mammary tumor bearing mice, the 111 In-DTPA was cleared rapidly from the blood with insignificant retention in the tumors.…”

“…Only 2 h after intravenous administration of 111 In-DTPA the largest retained dose was found in the kidneys, which only retained an average 0.126% injected dose/gram. 38 Li et al found that when studying the biodistribution of 111 In-DTPA in mammary tumor bearing mice, the 111 In-DTPA was cleared rapidly from the blood with insignificant retention in the tumors. 39 Overall, 111 In-DTPA alone is not well retained in vivo and rapidly cleared through the renal system unless it is anchored by a macromolecule or particle that is not readily cleared.…”

Metal-Based Complexes as Pharmaceuticals for Molecular Imaging of the Liver

“…Hexavalent lactoside modified with DTPA to chelate 111 In also exhibited nearly exclusive accumulation in rat and mice liver [175,176,177]. 111 In complexes of DTPA derivatives bearing aromatic moieties also exhibit mainly hepatobiliary excretion, comparably to their Gd(III) analogs [178,179].…”

Synthesis and Characterization of Ligands and their Gadolinium(III) Complexes

“…Series of bis(amide) derivatives was synthesized [4,[42][43][44][45][46], including macrocyclic derivatives, where two terminal carboxylates were bridged via a linear α,ω-diamine [45]. Bis(amides) containing various functionalities in the amide side chain were synthesized to allow conjugation of such ligands (and their complexes) to a polymeric scaffold (terminal alkyne group [47]) or their direct incorporation into polymer framework by condensation with linear diamines [4,48,49]; they serve as albumin-binding groups for angiographic applications (with a ferrocene unit [50]), lipophilic chains responsible for self-aggregation [51] or embedding into liposomes [52,53], glutathione moieties lately used for anchoring to gold nanoparticles [54], 4-(2-aminoethyl)phenol (tyramine) for detection of tyrosinase activity [55], lipophilic chains for detection of lipase activity [56], aminosugars [57], porphyrines [58], derivatives of bis[(pyrid-2-yl)methyl]amine resulting in zinc(II)-selective agents [59,60], sialyl-mimetic group [61], dendritic glycosidic moieties [62], trimethoxysilyl group in the side chain used for incorporation onto silica-layer-coated nanoparticles [63], and so on.…”