Show simple item record

3-[211At]astato-4-fluorobenzylguanidine: a potential therapeutic agent with prolonged retention by neuroblastoma cells.

dc.contributor.author Larsen, RH
dc.contributor.author Vaidyanathan, Ganesan
dc.contributor.author Zalutsky, Michael Rod
dc.contributor.author Zhao, XG
dc.coverage.spatial England
dc.date.accessioned 2015-12-03T18:28:12Z
dc.date.issued 1997
dc.identifier http://www.ncbi.nlm.nih.gov/pubmed/9231923
dc.identifier.issn 0007-0920
dc.identifier.uri https://hdl.handle.net/10161/11044
dc.description.abstract An analogue of meta-iodobenzylguanidine (MIBG) in which an aromatic hydrogen was replaced with fluorine has been found to possess many properties similar to those of the parent compound. Moreover, 4-fluoro-3-iodobenzylguanidine (FIBG) was retained in vitro by human neuroblastoma cells to a much greater extent than MIBG itself. Since alpha-emitters such as 211At could be valuable for the treatment of micrometastatic disease, an FIBG analogue in which the iodine atom is replaced by 211At would be of interest. In this study, we have evaluated the in vitro and in vivo properties of 3-[211At]astato-4-fluorobenzylguanidine ([211At]AFBG). The specific binding of [211At]AFBG to SK-N-SH human neuroblastoma cells remained fairly constant over 2- to 3-log activity range and was similar to that of [131I]MIBG. The uptake of [211At]AFBG by this cell line was reduced by desipramine, ouabain, 4 degrees C incubation, noradrenaline, unlabelled MIBG and FIBG, suggesting that its uptake is specifically mediated through an active uptake-1 mechanism. Over the 16 h period studied, the amount of [211At]AFBG retained was similar to that of [131I]FIBG, whereas the per cent of retained meta-[211At]astatobenzylguanidine ([211At]MABG) was considerably less than that of [131I]FIBG (53% vs 75%; P < 0.05). The IC50 values for the inhibition of uptake of [131I]MIBG, [211At]MABG, [125I]FIBG and [211At]AFBG by unlabelled MIBG were 209, 300, 407 and 661 nM respectively, suggesting that the affinities of these tracers for the noradrenaline transporter in SK-N-SH cells increase in that order. Compared with [211At]MABG, higher uptake of [211At]AFBG was seen in vivo in normal mouse target tissues such as heart and, to a certain extent, in adrenals. That the uptake of [211At]AFBG in these tissues was related to the uptake-1 mechanism was demonstrated by its reduction when mice were pretreated with desipramine. However, the stability of [211At]AFBG towards in vivo dehalogenation was less than that of [211At]MABG, as evidenced by the higher uptake of 211At in thyroid, spleen, lungs and stomach.
dc.language eng
dc.relation.ispartof Br J Cancer
dc.subject 3-Iodobenzylguanidine
dc.subject Animals
dc.subject Antineoplastic Agents
dc.subject Astatine
dc.subject Binding Sites
dc.subject Guanidines
dc.subject Humans
dc.subject Iodine Radioisotopes
dc.subject Iodobenzenes
dc.subject Male
dc.subject Mice
dc.subject Mice, Inbred BALB C
dc.subject Neuroblastoma
dc.subject Tissue Distribution
dc.subject Tumor Cells, Cultured
dc.title 3-[211At]astato-4-fluorobenzylguanidine: a potential therapeutic agent with prolonged retention by neuroblastoma cells.
dc.type Journal article
pubs.author-url http://www.ncbi.nlm.nih.gov/pubmed/9231923
pubs.begin-page 226
pubs.end-page 233
pubs.issue 2
pubs.organisational-group Clinical Science Departments
pubs.organisational-group Duke
pubs.organisational-group Duke Cancer Institute
pubs.organisational-group Institutes and Centers
pubs.organisational-group Pathology
pubs.organisational-group Radiation Oncology
pubs.organisational-group Radiology
pubs.organisational-group School of Medicine
pubs.publication-status Published
pubs.volume 76


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record