We report the synthesis, characterization, and utilization of radioactive (131)I-labeled multifunctional
dendrimers for targeted single-photon emission computed tomography (SPECT) imaging and
radiotherapy of
tumors. In this study,
amine-terminated
poly(amidoamine)
dendrimers of generation 5 (G5·NH2) were sequentially modified with 3-(4'-hydroxyphenyl)propionic
acid-OSu (HPAO) and
folic acid (FA) linked with
polyethylene glycol (PEG), followed by acetylation modification of the
dendrimer remaining surface
amines and labeling of radioactive
iodine-131 ((131)I). The generated multifunctional (131)I-G5·NHAc-HPAO-PEG-FA
dendrimers were characterized via different methods. We show that prior to (131)I labeling, the G5·NHAc-HPAO-PEG-FA
dendrimers conjugated with approximately 9.4 HPAO moieties per
dendrimer are noncytotoxic at a concentration up to 20 μM and are able to target
cancer cells overexpressing FA receptors (FAR), thanks to the modified FA
ligands. In the presence of a
phenol group, radioactive (131)I is able to be efficiently labeled onto the
dendrimer platform with good stability and high radiochemical purity, and render the platform with an ability for targeted SPECT imaging and
radiotherapy of an FAR-overexpressing xenografted
tumor model in vivo. The designed strategy to use the facile
dendrimer nanotechnology may be extended to develop various radioactive
theranostic nanoplatforms for targeted SPECT imaging and
radiotherapy of different types of
cancer.