Biodistribution of 89Zr-Radiolabeled Nanoassemblies for Monoclonal Antibody Delivery Revealed through in vivo PET Imaging

Ana M.  Lopez Estevez; Amaia Minino; Dolores Torres; Maria Jose Alonso; Rafael T. M. de Rosales; Juan Pellico Saez

doi:10.1021/acsomega.4c09823

Biodistribution of ⁸⁹Zr-Radiolabeled Nanoassemblies for Monoclonal Antibody Delivery Revealed through in vivo PET Imaging

Ana M. Lopez Estevez, Amaia Minino, Dolores Torres, Maria Jose Alonso, Rafael T. M. de Rosales^*, Juan Pellico Saez

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

Abstract

Despite the outstanding performance of monoclonal antibodies (mAbs) in the clinic, their full potential has been hindered due to their inability to cross cell membranes and therefore reach intracellular targets. The use of nanotechnology to deliver mAbs to intracellular domains has been highlighted as a strategy with high potential. Working toward this goal, we have recently developed and validated palmitoyl hyaluronate (HAC16)-based nanoassemblies (HANAs), a novel technology for the intracellular delivery of mAbs in Kirsten Rat Sarcoma Virus (KRAS)-mutated tumors, one of the most prevalent and a challenging intracellular oncoprotein. Despite their success, the pharmacokinetics and biodistribution of these delivery vehicles are still unknown due to their chemical complexity, a challenge common to a large proportion of drug delivery nanomedicines. To support further development and clinical translation, we present an efficient radiolabeling approach with the positron emitter zirconium-89 (89Zr) for the in vivo evaluation of HANAs by whole-body PET imaging. Additionally, we assessed the impact of PEGylation and size modulation on the biodistribution profile of mAbs using 89Zr-radiolabeled PEGylated and non-PEGylated HANAs. Our PET imaging results demonstrated that HANAs significantly modify the pharmacokinetics and biodistribution of the 89Zr-mAb. Furthermore, we established that the biodistribution of HANAs can be conveniently modulated by introducing PEG polymers on the surface, facilitating customization for cancer applications. This versatile radiolabeling strategy provides a facile approach for the in vivo evaluation of complex nanoformulations loaded with mAbs, in a quantitative manner with high sensitivity.

Original language	English
Pages (from-to)	4763-4773
Number of pages	11
Journal	ACS Omega
Volume	10
Issue number	5
DOIs	https://doi.org/10.1021/acsomega.4c09823
Publication status	Published - 11 Feb 2025

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1021/acsomega.4c09823Licence: CC BY

Cite this

@article{f959dbc6c7f7403db98a06eac6cd94d5,

title = "Biodistribution of 89Zr-Radiolabeled Nanoassemblies for Monoclonal Antibody Delivery Revealed through in vivo PET Imaging",

abstract = "Despite the outstanding performance of monoclonal antibodies (mAbs) in the clinic, their full potential has been hindered due to their inability to cross cell membranes and therefore reach intracellular targets. The use of nanotechnology to deliver mAbs to intracellular domains has been highlighted as a strategy with high potential. Working toward this goal, we have recently developed and validated palmitoyl hyaluronate (HAC16)-based nanoassemblies (HANAs), a novel technology for the intracellular delivery of mAbs in Kirsten Rat Sarcoma Virus (KRAS)-mutated tumors, one of the most prevalent and a challenging intracellular oncoprotein. Despite their success, the pharmacokinetics and biodistribution of these delivery vehicles are still unknown due to their chemical complexity, a challenge common to a large proportion of drug delivery nanomedicines. To support further development and clinical translation, we present an efficient radiolabeling approach with the positron emitter zirconium-89 (89Zr) for the in vivo evaluation of HANAs by whole-body PET imaging. Additionally, we assessed the impact of PEGylation and size modulation on the biodistribution profile of mAbs using 89Zr-radiolabeled PEGylated and non-PEGylated HANAs. Our PET imaging results demonstrated that HANAs significantly modify the pharmacokinetics and biodistribution of the 89Zr-mAb. Furthermore, we established that the biodistribution of HANAs can be conveniently modulated by introducing PEG polymers on the surface, facilitating customization for cancer applications. This versatile radiolabeling strategy provides a facile approach for the in vivo evaluation of complex nanoformulations loaded with mAbs, in a quantitative manner with high sensitivity.",

author = "{Lopez Estevez}, {Ana M.} and Amaia Minino and Dolores Torres and Alonso, {Maria Jose} and {T. M. de Rosales}, Rafael and {Pellico Saez}, Juan",

note = "Publisher Copyright: {\textcopyright} 2025 The Authors. Published by American Chemical Society.",

year = "2025",

month = feb,

day = "11",

doi = "10.1021/acsomega.4c09823",

language = "English",

volume = "10",

pages = "4763--4773",

journal = "ACS Omega",

issn = "2470-1343",

publisher = "American Chemical Society",

number = "5",

}

TY - JOUR

T1 - Biodistribution of 89Zr-Radiolabeled Nanoassemblies for Monoclonal Antibody Delivery Revealed through in vivo PET Imaging

AU - Lopez Estevez, Ana M.

AU - Minino, Amaia

AU - Torres, Dolores

AU - Alonso, Maria Jose

AU - T. M. de Rosales, Rafael

AU - Pellico Saez, Juan

PY - 2025/2/11

Y1 - 2025/2/11

N2 - Despite the outstanding performance of monoclonal antibodies (mAbs) in the clinic, their full potential has been hindered due to their inability to cross cell membranes and therefore reach intracellular targets. The use of nanotechnology to deliver mAbs to intracellular domains has been highlighted as a strategy with high potential. Working toward this goal, we have recently developed and validated palmitoyl hyaluronate (HAC16)-based nanoassemblies (HANAs), a novel technology for the intracellular delivery of mAbs in Kirsten Rat Sarcoma Virus (KRAS)-mutated tumors, one of the most prevalent and a challenging intracellular oncoprotein. Despite their success, the pharmacokinetics and biodistribution of these delivery vehicles are still unknown due to their chemical complexity, a challenge common to a large proportion of drug delivery nanomedicines. To support further development and clinical translation, we present an efficient radiolabeling approach with the positron emitter zirconium-89 (89Zr) for the in vivo evaluation of HANAs by whole-body PET imaging. Additionally, we assessed the impact of PEGylation and size modulation on the biodistribution profile of mAbs using 89Zr-radiolabeled PEGylated and non-PEGylated HANAs. Our PET imaging results demonstrated that HANAs significantly modify the pharmacokinetics and biodistribution of the 89Zr-mAb. Furthermore, we established that the biodistribution of HANAs can be conveniently modulated by introducing PEG polymers on the surface, facilitating customization for cancer applications. This versatile radiolabeling strategy provides a facile approach for the in vivo evaluation of complex nanoformulations loaded with mAbs, in a quantitative manner with high sensitivity.

AB - Despite the outstanding performance of monoclonal antibodies (mAbs) in the clinic, their full potential has been hindered due to their inability to cross cell membranes and therefore reach intracellular targets. The use of nanotechnology to deliver mAbs to intracellular domains has been highlighted as a strategy with high potential. Working toward this goal, we have recently developed and validated palmitoyl hyaluronate (HAC16)-based nanoassemblies (HANAs), a novel technology for the intracellular delivery of mAbs in Kirsten Rat Sarcoma Virus (KRAS)-mutated tumors, one of the most prevalent and a challenging intracellular oncoprotein. Despite their success, the pharmacokinetics and biodistribution of these delivery vehicles are still unknown due to their chemical complexity, a challenge common to a large proportion of drug delivery nanomedicines. To support further development and clinical translation, we present an efficient radiolabeling approach with the positron emitter zirconium-89 (89Zr) for the in vivo evaluation of HANAs by whole-body PET imaging. Additionally, we assessed the impact of PEGylation and size modulation on the biodistribution profile of mAbs using 89Zr-radiolabeled PEGylated and non-PEGylated HANAs. Our PET imaging results demonstrated that HANAs significantly modify the pharmacokinetics and biodistribution of the 89Zr-mAb. Furthermore, we established that the biodistribution of HANAs can be conveniently modulated by introducing PEG polymers on the surface, facilitating customization for cancer applications. This versatile radiolabeling strategy provides a facile approach for the in vivo evaluation of complex nanoformulations loaded with mAbs, in a quantitative manner with high sensitivity.

UR - http://www.scopus.com/inward/record.url?scp=85216485345&partnerID=8YFLogxK

U2 - 10.1021/acsomega.4c09823

DO - 10.1021/acsomega.4c09823

M3 - Article

SN - 2470-1343

VL - 10

SP - 4763

EP - 4773

JO - ACS Omega

JF - ACS Omega

IS - 5

ER -

Biodistribution of ⁸⁹Zr-Radiolabeled Nanoassemblies for Monoclonal Antibody Delivery Revealed through in vivo PET Imaging

Abstract

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this