Hyperbranched polysulfonamine (HPSA) is a promising biomaterial due to its highly branched spherical architecture and efficient intracellular translocation. To realize the functionalization of HPSA

both

N

-succinimidyl 3-(2- pyridyldithio) propionate (SPDP) for tethering the human-mouse chimeric monoclonal antibody CH12 and

N

-hydroxy succinimidyl

S

-acetylmercaptoacetyltriglycinate (NHS-MAG

3

) for labeling

188

Re were sequentially grafted onto the primary amine terminals of HPSA

via

covalent linkages

attaining the SPDP-HPSA-MAG

3

intermediate. In order to reserve the structural integrity of CH12

the fragment crystallizable (Fc) region was also processed by oxidation of oligosaccharide moieties with sodium periodate and then reacted with

N

-(

κ

-maleimidoundecanoic acid) hydrazide (KMUH). After chelating

188

Re with MAG

3

group

the SPDP was reduced to PDP and connected onto the maleinimide group at the Fc region. As a result

both the epidermal growth factor receptor vIII (EGFRvIII) targeted monoclonal antibody CH12 and the radionuclide

188

Re were conjugated to the HPSA-based vehicles

forming the

188

Re-labeled and CH12-tethered HPSA (CH12-HPSA-

188

Re). The molecular weight and

in vitro

stability of CH12-HPSA-

188

Re were evaluated by gel electrophoresis and paper chromatography. On one hand

the CH12-HPSA-

188

Re could specifically bind to the EGFRvIII-positive human hepatocarcinoma cells

in vitro

. On the other hand

it could also target at the tumor tissue of nude mice

in vivo

. Hence

the CH12-HPSA-

188

Re could effectively target at the human hepatocarcinoma and facilitate the tumor detection and targeted radioimmunotherapy.