Linear Desferrichrome-Linked Silicon-Rhodamine Antibody Conjugate Enables Targeted Multimodal Imaging of HER2 in Vitro and in Vivo.
Mol Pharm
; 16(3): 1412-1420, 2019 03 04.
Article
en En
| MEDLINE
| ID: mdl-30714739
ABSTRACT
We report the nuclear and optical in vitro and in vivo imaging of SKOV-3 cells by targeting HER2 with a bimodal trastuzumab conjugate. Previously, we have shown that desferrichrome derivatives provide a robust and versatile radiolabeling platform for the radioisotope zirconium-89. Here, we appended silicon-rhodamine functionalized linear desferrichrome to trastuzumab. This construct was radiolabeled and used to image cellular binding and antibody uptake in vitro and in vivo. The robust extinction coefficient of the SiR deep-red emissive fluorophore enables direct quantification of the number of appended chelators and fluorophore molecules per antibody. Subsequent radiolabeling of the multifunctional immunoconjugate with 89Zr was achieved with a 64 ± 9% radiochemical yield, while the reference immunoconjugate desferrioxamine (DFO)-trastuzumab exhibited a yield of 84 ± 9%. In vivo PET imaging (24, 48, 72, and 96 h post injection) and biodistribution experiments (96 h post injection) in HER2+ tumor bearing mice revealed no statistically significant difference of the two 89Zr-labeled conjugates at each time point evaluated. The bimodal conjugate permitted successful in vivo fluorescence imaging (96 h post injection) and subsequent fluorescence-guided, surgical resection of the tumor mass. This report details the first successful application of a fluorophore-functionalized desferrichrome derivative for targeted imaging, motivating further development and application of this scaffold as a multimodal imaging platform.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Rodaminas
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Silicio
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Receptor ErbB-2
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Radiofármacos
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Deferoxamina
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Trastuzumab
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Tomografía Computarizada por Tomografía de Emisión de Positrones
Límite:
Animals
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Female
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Humans
Idioma:
En
Revista:
Mol Pharm
Asunto de la revista:
BIOLOGIA MOLECULAR
/
FARMACIA
/
FARMACOLOGIA
Año:
2019
Tipo del documento:
Article
País de afiliación:
Estados Unidos