PET Imaging Using 89Zr-Labeled StarPEG Nanocarriers Reveals Heterogeneous Enhanced Permeability and Retention in...

Area of Science:

• Biomedical Engineering
• Radiochemistry
• Oncology

Background:

• The enhanced permeability and retention (EPR) effect influences nanodrug delivery in cancer, but its efficacy varies with cancer type.
• Predicting EPR-mediated drug delivery is crucial for optimizing nanotherapeutic strategies.
• Developing imaging tools to assess tumor-specific EPR is essential for personalized cancer treatment.

Purpose of the Study:

• To develop and evaluate 89Zr-radiolabeled nanocarriers as positron emission tomography (PET) imaging surrogates for the enhanced permeability and retention (EPR) effect.
• To assess the ability of these nanocarriers to predict nanodrug uptake and distribution in various cancer models, including prostate cancer xenografts.
• To investigate the correlation between nanocarrier penetration, tumor vascularization, and EPR-mediated uptake.

Main Methods:

• Synthesis of two 89Zr-radiolabeled nanocarriers based on 4-armed star polyethylene glycol (PEG) with or without talazoparib (TLZ).
• Radiolabeling with 89Zr by incorporating deferoxamine B (DFB) onto the PEG scaffold.
• In vivo evaluation using microPET/CT imaging, biodistribution studies, and autoradiography in subcutaneous and metastatic prostate cancer xenografts and a high-EPR CT26 cell line.
• Tumor vascularization assessment via CD31 staining.

Main Results:

• The 89Zr-radiolabeled nanocarriers ([89Zr]PEG-DFB4 and [89Zr]PEG-DFB1-TLZ3) demonstrated high uptake in the high-EPR CT26 model and LTL-545 xenografts, with moderate to low uptake in LTL-610 and 22Rv1 models.
• Nanocarrier penetration was observed in highly permeable CT26 tumors, but heterogeneous peripheral accumulation occurred in other xenografts and metastatic models.
• Tumor vascularization was homogenous in CT26 but heterogeneous in other xenografts, correlating with observed nanocarrier distribution.
• Both nanocarriers showed similar accumulation and distribution patterns, indicating their utility in measuring passive uptake heterogeneity across different tumor models.

Conclusions:

• 89Zr-labeled starPEG nanocarriers serve as effective PET imaging surrogates to assess tumor-specific EPR heterogeneity.
• These nanocarriers can predict variations in nanodrug delivery and distribution, particularly in challenging models like prostate cancer xenografts.
• The findings support the use of such imaging surrogates for guiding personalized nanotherapeutic strategies in oncology.