Assessment of 177 Lu-labeled carboxyl-terminated polyamidoamine (PAMAM) dendrimer-RGD peptide conjugate.
J Pept Sci
; 28(2): e3366, 2022 Feb.
Article
em En
| MEDLINE
| ID: mdl-34463002
ABSTRACT
Structurally unique polyamidoamine (PAMAM) dendrimers implanted with targeting biological moiety along with complexed radiometal constitute a favorable nano-system for diagnosis and therapy of targeted tumor sites. In the present study, carboxyl functionalities of PAMAM- generation 4 dendrimer (PAMAM-G4-COOH) were conjugated with ε-amino group of lysine of cRGDfK peptide to impart integrin αv ß3 targeting capability. Reaction of p-NH2 -Bn-DOTA with PAMAM was accomplished via acid-amine coupling using EDC/NHS for 177 Lu-complexation. 177 Lu-labeled nano-system, 177 Lu-PAMAM-DOTA-cRGDfK demonstrated receptor-mediated uptake in murine melanoma B16F10 cells during in vitro cell uptake studies. In vivo biodistribution studies demonstrated low tumor uptake and retention of 177 Lu-PAMAM-DOTA-cRGDfK which may be attributed to rapid blood clearance. However, fast clearance from non-target organs resulted in higher target to background ratio. Tumor uptake of targeted nano-system, 177 Lu-PAMAM-DOTA-cRGDfK was observed to be significantly (p < 0.05) higher in comparison to 177 Lu-PAMAM-DOTA without the targeting peptide. Inhibition studies with unlabeled cRGDfK resulted in 60% reduction in tumor uptake of 177 Lu-PAMAM-DOTA-cRGDfK, indicating specificity of the developed nano-system towards integrin αv ß3 receptors.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Dendrímeros
Limite:
Animals
Idioma:
En
Revista:
J Pept Sci
Assunto da revista:
BIOQUIMICA
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
Índia