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

dc.contributor.author

Vaidyanathan, G

dc.contributor.author

Zhao, XG

dc.contributor.author

Larsen, RH

dc.contributor.author

Zalutsky, MR

dc.coverage.spatial

England

dc.date.accessioned

2015-12-03T18:28:12Z

dc.date.issued

1997

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.identifier

http://www.ncbi.nlm.nih.gov/pubmed/9231923

dc.identifier.issn

0007-0920

dc.identifier.uri

https://hdl.handle.net/10161/11044

dc.language

eng

dc.publisher

CHURCHILL LIVINGSTONE

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

duke.contributor.orcid

Vaidyanathan, G|0000-0003-3041-8275

duke.contributor.orcid

Zalutsky, MR|0000-0002-5456-0324

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

Original bundle

Now showing 1 - 1 of 1
Loading...
Thumbnail Image
Name:
3-[211At]astato-4-fluorobenzylguanidine: a potential therapeutic agent with prolonged retention by neuroblastoma cells.pdf
Size:
1.34 MB
Format:
Adobe Portable Document Format