Interferon-gamma-induced differentiation of human neuroblastoma cells increases cellular uptake and halflife of metaiodobenzylguanidine.
Iodine labeled metaiodobenzylguanidine (MIBG) is a radiopharmaceutical employed for both diagnosis and metabolic radiotherapy of neuroblastoma (NB). Resistance to the radiotherapeutic effects of MIBG is common, due to lack of MIBG accumulation by NB cells. MIBG enters competent cells via the noradrenaline transporter; this function requires a relative cellular maturation and is missing in most NB cell lines. In vitro differentiation of NB cells can be achieved with gamma-interferon (gamma-IFN) and other agents. We have verified that gamma-IFN-induced differentiation of NB cells is specifically associated with an increase in their ability to incorporate MIBG. This phenomenon is due to enhancement of MIBG transporter activity, according to pharmacological sensitivity and semiquantitative PCR-based analysis of specific MIBG transporter mRNA. New therapeutic strategies based on both differentiation therapy and targeted radiotherapy of NB can so be devised.
Montaldo
P G
PG
Oncology Res. Lab., G. Gaslini Children's Hosp., Genoa, Italy.
Carbone
R
R
Cornaglia Ferraris
P
P
Ponzoni
M
M
D019797:3-Iodobenzylguanidine; D001693:Biological Transport, Active / Q000187:drug effects; D001709:Biotechnology; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D006207:Half-Life; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics* / Q000627:therapeutic use; D007462:Iodobenzenes / Q000493:pharmacokinetics* / Q000627:therapeutic use; D009447:Neuroblastoma / Q000378:metabolism* / Q000473:pathology / Q000532:radiotherapy; D012333:RNA, Messenger / Q000378:metabolism; D011994:Recombinant Proteins
D007457:Iodine Radioisotopes; D007462:Iodobenzenes; D012333:RNA, Messenger; D011994:Recombinant Proteins; D019797:3-Iodobenzylguanidine; D007371:Interferon-gamma