177Lu-labeled RGD-BBN heterodimeric peptide for targeting prostate carcinoma.
Nucl Med Commun
; 34(9): 909-14, 2013 Sep.
Article
en En
| MEDLINE
| ID: mdl-23708872
ABSTRACT
INTRODUCTION:
Radiolabeled Arg-Gly-Asp (RGD) and bombesin (BBN) heterodimers have been investigated for dual targeting of tumor integrin αvß3 receptors and gastrin-releasing peptide receptors. The goal of this study was to evaluate the potential use of a Lu-labeled RGD-BBN heterodimer for targeted prostate cancer therapy. MATERIALS ANDMETHODS:
A 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid-conjugated RGD-BBN peptide (DO3A-RGD-BBN) was radiolabeled with Lu and purified by high-performance liquid chromatography. The in-vivo biodistribution study of Lu-DO3A-RGD-BBN was carried out in mice bearing human prostate cancer PC3 xenografts. The receptor-targeting specificity of the radiolabeled peptide was assayed by injecting the tracer with the unlabeled RGD-BBN peptide. Radiation absorbed doses in adult male patients, based on biodistribution data from mice, were also calculated.RESULTS:
DO3A-RGD-BBN peptides were successfully labeled with Lu, and high radiochemical purity (>95%) could be achieved after high-performance liquid chromatography purification. In human PC3 xenograft-bearing mice, the tumor accumulation of Lu-DO3A-RGD-BBN was 5.88±1.12, 2.77±0.30, 2.04±0.19, and 1.18±0.19%ID/g at 0.5, 2, 24, and 48 h, respectively. With rapid clearance from normal tissues, the radiolabeled probe displayed high tumor-to-blood and tumor-to-muscle ratios. On calculating the radiation absorbed doses for Lu-DO3A-RGD-BBN, we found that the prostate tumor and the pancreas were the organs receiving the highest radiation absorbed doses.CONCLUSION:
Dual integrin αvß3 and GPRP-targeted agent Lu-DO3A-RGD-BBN shows excellent prostate cancer-targeting ability, and it is worthy of further evaluation for prostate cancer-targeted therapy.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Oligopéptidos
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Neoplasias de la Próstata
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Bombesina
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Dimerización
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Terapia Molecular Dirigida
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Lutecio
Límite:
Animals
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Humans
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Male
Idioma:
En
Revista:
Nucl Med Commun
Año:
2013
Tipo del documento:
Article
País de afiliación:
China