In vitro therapeutic targeting of neuroblastomas using 125I-labelled meta-iodobenzylguanidine.
The use of labelled radiopharmaceuticals such as metaiodobenzylguanidine (m-IBG) enables neuroblastomas and other malignant cells from neural crests to be visualized. In vitro study of cellular incorporation into human neuroblastoma lines (SK-N-SH, SK-N-MC, LAN I) showed that only the SK-N-SH line retained iodine-125 m-IBG (125I-m-IBG) significantly. Fifty-five percent of the initial activity was retained after 1 hr incubation at a concentration of 10(-7) M of m-IBG (specific activity: 1,480 MBq/mg). Beyond this value, m-IBG uptake mechanisms were saturated. Study of release kinetics showed a rapid first phase (50% released after 4 hr) and a slower second phase (30% of the value retained at the equilibrium point was present after 48 hr), indicating the existence of a storage compartment. Autoradiography studies confirmed the intracytoplasmic localization of m-IBG and showed that a low percentage (3 to 5%) of SK-N-SH cells strongly retained m-IBG. Cytotoxicity tests showed that SK-N-SH cell growth was significantly reduced during the first days of culture, following 2 hr incubation with 1,500 KBq of 125I-m-IBG, whereas no toxic effect on SK-N-MC cells was found at the same activity. Moreover, the toxic effect observed in the SK-N-SH line was clearly related to the use of 125I-m-IBG since the same activity of 1,500 KBq of non-coupled 125I was without effect. For the latter line, colony-forming capacity was reduced for activities of 150 and 1,500 KBq of 125I-m-IBG, with respectively 32% and 38% lower survival rates. The cytotoxic effect of labelled m-IBG was, however, limited in non-saturating concentrations because the specific activity used was too low. Moreover, the low number of cells reconcentrating m-IBG is indicative of the heterogeneous cellular composition of the SK-N-SH line.
Guerreau
D
D
CEA/IPSN/DPS/STCE/LTT, BP 12, Bruyères le Chatel, France.
Thedrez
P
P
Fritsch
P
P
Saccavini
J C
JC
Metivier
H
H
Nolibe
D
D
Masse
R
R
Coornaert
S
S
Chatal
J F
JF
D019797:3-Iodobenzylguanidine; D001345:Autoradiography; D002460:Cell Line; D003114:Colony-Forming Units Assay; D003287:Contrast Media / Q000493:pharmacokinetics* / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007457:Iodine Radioisotopes / Q000633:toxicity; D007462:Iodobenzenes / Q000493:pharmacokinetics* / Q000633:toxicity; D009447:Neuroblastoma / Q000000981:diagnostic imaging / Q000378:metabolism*; D011877:Radionuclide Imaging; D013997:Time Factors; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism
D003287:Contrast Media; D007457:Iodine Radioisotopes; D007462:Iodobenzenes; D019797:3-Iodobenzylguanidine