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177 Lu‐labeled monomeric, dimeric and multimeric RGD peptides for the therapy of tumors expressing α ( ν ) β (3) integrins
Author(s) -
LunaGutiérrez Myrna,
FerroFlores Guillermina,
OcampoGarcía Blanca,
JiménezMancilla Nallely,
MoralesAvila Enrique,
De LeónRodríguez Luis,
IsaacOlivé Keila
Publication year - 2012
Publication title -
journal of labelled compounds and radiopharmaceuticals
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.432
H-Index - 47
eISSN - 1099-1344
pISSN - 0362-4803
DOI - 10.1002/jlcr.2910
Subject(s) - chemistry , dota , conjugated system , monomer , peptide , integrin , stereochemistry , colloidal gold , cysteine , dimer , nuclear chemistry , ligand (biochemistry) , chelation , nanoparticle , receptor , biochemistry , enzyme , organic chemistry , nanotechnology , materials science , polymer
The conjugation of peptides to gold nanoparticles (AuNPs) produces biocompatible and stable multimeric systems with target‐specific molecular recognition. Peptides based on the cyclic Arg‐Gly‐Asp (RGD) sequence have been reported as high‐affinity agents for the α ( ν ) β (3) integrin. The aim of this research was to prepare a multimeric system of 177 Lu‐labeled gold nanoparticles conjugated to c(RGDfK)C (cyclo(Arg‐Gly‐Asp‐Phe‐Lys)Cys) and to compare the radiation‐absorbed dose with that of 177 Lu‐labeled monomeric and dimeric RGD peptides to α ( ν ) β (3) integrin‐positive U87MG tumors in mice. DOTA‐GGC (1,4,7,10‐tetraazacyclododecane‐N‐N′,N″,N‴‐tetraacetic acid‐Gly‐Gly‐Cys) and c(RGDfK)C peptides were synthesized and conjugated to AuNPs by a spontaneous reaction of the thiol groups. Transmission electron microscopy, ultraviolet–visible, X‐ray photoelectron spectroscopy, Raman and far‐infrared spectroscopy techniques demonstrated that AuNPs were functionalized with the peptides. For the 177 Lu‐AuNP‐c(RGDfK)C to be obtained, the 177 Lu‐DOTA‐GGC radiopeptide was first prepared and added to a solution of AuNPs followed by c(RGDfK)C (25 µl, 5 µ m ) at 18 °C for 15 min. 177 Lu‐DOTA‐GGC, 177 Lu‐DOTA‐cRGDfK and 177 Lu‐DOTA‐E‐c(RGDfK) 2 were prepared by adding 177 LuCl 3 (370 MBq) to 5 µl (1 mg/ml) of the DOTA derivative diluted with 50 µl of 1 m acetate buffer pH 5. The mixture was incubated at 90 °C in a block heater for 30 min. Radiochemical purity was determined by ultrafiltration and HPLC analyses. Biokinetic studies were accomplished in athymic mice with U87MG‐induced tumors. The radiochemical purity for all 177 Lu‐RGD derivatives was 96 ± 2%. 177 Lu‐absorbed doses per injected activity delivered to U87MG tumors were 0.357 ± 0.052 Gy/MBq (multimer), 0.252 ± 0.027 Gy/MBq (dimer) and 0.102 ± 0.018 Gy/MBq (monomer). 177 Lu‐labeled dimeric and multimeric RGD peptides demonstrated properties suitable for targeted radionuclide therapy of tumors expressing α ( ν ) β (3) integrins. Copyright © 2012 John Wiley & Sons, Ltd.