Is MIBG a substrate of P-glycoprotein?
OBJECTIVE
Radionuclide therapy with 131I-labelled meta-iodobenzylguanidine ([131I]MIBG) is effective in cases where it is difficult to carry out surgical resection or debulking of neuroendocrine tumours (NETs). However, it has recently been reported that P-glycoprotein (P-gp) is expressed in these NETs. Therefore, it is important to clarify whether MIBG is a substrate of P-gp or not. In this study, using a human cell line which overexpresses P-gp, LLC-GA5-COL150, we investigated this question.


METHODS
The transcellular transport and accumulation of [125I]MIBG were measured using monolayer cultures grown in Transwell chambers. [125I]MIBG was added to either the basolateral or the apical side, aliquots of the incubation medium on the other side were taken at specified times, and the radioactivity was measured. For accumulation experiments, the cells on the filters were solubilised and the radioactivity in aliquots was measured.


RESULTS
There were no significant differences in the transport of MIBG between LLC-PK1 and LLC-GA5-COL150 monolayers in either direction until 60 min. With respect to the accumulation of MIBG, there were no significant differences between LLC-PK1 and LLC-GA5-COL150 cells in either direction.


CONCLUSIONS
MIBG is not a substrate of P-gp. Therefore, radionuclide therapy with MIBG would be useful in the treatment of NETs expressing P-gp.
Kiyono
Yasushi
Y
Radioisotopes Research Laboratory, Faculty of Medicine, Kyoto University Hospital, Kyoto University, Kyoto, Japan.
Yamashita
Tomoko
T
Doi
Hisako
H
Kuge
Yuji
Y
Katsura
Toshiya
T
Inui
Ken-ichi
K
Saji
Hideo
H
D019797:3-Iodobenzylguanidine / Q000493:pharmacokinetics*; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D000818:Animals; D002460:Cell Line; D007668:Kidney / Q000378:metabolism*; D008657:Metabolic Clearance Rate; D011485:Protein Binding; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D013552:Swine
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D019275:Radiopharmaceuticals; D019797:3-Iodobenzylguanidine