A new potencial radiopharmaceutical product for tumour diagose: PAMAM G4 dendrimers labeded with 99mTcTricarbonyl

GABRIELA NAVARRO; PABLO CABRAL; PAOLA AUDICIO; VICTORIA TRINDADE; MARCELO FERNANDEZ; JUAN PABLO GAMBINI; EMILIA REZZANO; MARÍA JOSÉ MORILLA; JIMENA PRIETO; ANA ROBLES; EDER ROMERO; HENIA BALTER

Amsterdam, Noord-Holland, Netherlands

Congreso; Pharmaceutical Sciences World Congress; 2007

Dendrimers PAMAM G4 (NH2) are polymeric nanosystems with special properties like their nanometric size, low dispersion and defined superficial structure. Their superficial amine groups allows the possibility to coordinate with radionuclides directly or through other ligands. radiolabelled dendrimers have high potential as scintigraphic imaging agents for tumor diagnosis.We studied the radiolabelling of PAMAM G4 (NH2) by using the strategy of 99mTc tricarbonyl complex and its evaluation in CD1 female mice having spontaneous breast cancer as well as in healthy mice.[99mTc (CO) 3(H2O) 3]+ was obtained by addition of 1 mL of 99mTcO4- (5-30 mCi) to a IsoLink (Mallinckrodt) kit, incubating for 20 minutes at 100ºC. 5 ıL (5.8 ımol/mL) of dendrimers solution wasadded to 100ıL (1mCi) of [99mTc(CO)3(H2O)3]+ and incubated 15 minutes at RT.Labelling efficiency and stability were evaluated by chromatography and gel filtration (PD-10 column G-25,eluent phosphate buffer 0.05 M pH 7.0).Biodistribution studies were done in CD1 female healthy mice, age 2 months, weight 30±1 g (n=3) and infemale mice with breast cancer, at different incubation times.Labelling yield was 99%, remaining 95% of the radionuclide bound to dendrimers for at least 2 hours post labelling. Elution volume in PD-10 columns was 6-8mL for [99mTc(CO)3(H2O)3]+ and 3-4mL for radiolabelled dendrímeros.Biodistribution in healthy mice shows uptake in spleen, liver, kidney, stomach and gastrointestinal tract. Tumour/Muscle ratio (activity %/g) was is 4.4 for mice with breast cancer.We can conclude that dendrimers PAMAM G4 (NH2) labelled through [99mTc(CO)3(H2O)3]+ complex shows good potential as radiopharmaceutical for tumour diagnosis and further research is warranted.