Triple targeting of Auger emitters using octreotate conjugated to a DNA-binding ligand and a nuclear localizing signal.
Int J Radiat Biol
; 92(11): 707-715, 2016 11.
Article
em En
| MEDLINE
| ID: mdl-27010622
ABSTRACT
PURPOSE:
We investigated the effect of incorporation of a nuclear localization signal (NLS) into a conjugate comprising the DNA binding ligand para-iodoHoechst (PIH) and octreotate on its DNA binding and affinity to the somatostatin receptor (SSTR). Confirmation of these properties would support development of similar conjugates labelled with Auger emitters for their potential in Auger endoradiotherapy. MATERIALS ANDMETHODS:
We synthesized conjugates of PIH and octreotate (PO) or PIH and NLS (PN) and a conjugate comprising PIH, NLS and octreotate (PNO). DNA-binding characteristics of PIH and conjugates were assessed using synthetic DNA oligonucleotides employing spectrophotometric titration of ligand solutions with DNA. We used membranes from the type 2 SSTR (SSTR2) overexpressing human non-small cell lung cancer cell line A427-7 to investigate the binding affinity of PNO.RESULTS:
We demonstrated PN and PNO retain specific high affinity DNA-binding properties observed for PIH, and acquire an additional non-specific binding capacity. No DNA binding was observed for PO. PNO retains its binding affinity for SSTR.CONCLUSIONS:
The DNA-binding properties of PNO and its affinity for SSTR suggests that it could potentially be used for tumour-specific delivery of PIH labelled with an Auger emitter in SSTR expressing tumours.Palavras-chave
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Peptídeos Cíclicos
/
DNA de Neoplasias
/
Receptores de Somatostatina
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Carcinoma Pulmonar de Células não Pequenas
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Sinais de Localização Nuclear
/
Radioisótopos do Iodo
Limite:
Humans
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article